RARE DISEASE
Thymic carcinoma
Thymic carcinoma
Thymic carcinoma
Synonyms: Malignant thymoma
Synonyms: Malignant thymoma
Synonyms: Malignant thymoma
Drug discovery
1
drug
With orphan designation
Overview
Thymic carcinoma is a rare, aggressive mediastinal malignancy arising from thymic epithelial cells, accounting for 0.07–0.38 cases per 100,000 annually [2][5][12]. It typically presents with locally invasive or metastatic disease, necessitating multimodal treatment. Histologically distinct from thymoma, it demonstrates poor differentiation and frequent TP53 mutations [5][16].
Therapies
Surgery: First-line for resectable tumors, often combined with adjuvant radiotherapy (50–75% 5-year survival post-R0 resection) [5][8]
Systemic therapy: Platinum-based regimens (e.g., carboplatin/paclitaxel) for advanced disease; emerging role for lenvatinib/pembrolizumab combinations [3][13][16]
Radiation: Used neoadjuvantly, adjuvantly, or palliatively; improves local control in incompletely resected cases [5][8]
Categories: rare neoplastic diseases
Research Papers
1,446 drug discovery papers about Thymic carcinoma, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,446 drug discovery papers about Thymic carcinoma, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-07-01 | 153P Efficacy and safety of lenvatinib in patients with thymic epithelial tumors: A retrospective, multicenter study
Thymic epithelial tumors (TETs) are rare malignancies with limited options after standard platinum-based chemotherapy. While the REMORA trial confirmed the efficacy of lenvatinib, a multi-targeted tyrosine kinase inhibitor (TKI), in thymic carcinoma (TC) patients with progressive disease, data for broader TET subtypes remain scarce. This study evaluated lenvatinib's efficacy and safety in patients with TETs, including TC and advanced malignant thymoma.
2026-05-29 | Advances in Pharmacological Treatment of Thoracic Malignancies.
Lung cancer remains the leading cause of cancer-related death worldwide, with over two million new cases annually. Advances in molecular biology and immuno-oncology have fundamentally transformed treatment strategies. Comprehensive genomic profiling has enabled precision medicine approaches, allowing the selection of targeted therapies based on driver alterations such as EGFR, ALK, and HER2. For EGFR-mutant NSCLC, sequential development of tyrosine kinase inhibitors (TKIs) from first- to third-generation agents-culminating in osimertinib-has markedly improved survival. Similarly, successive generations of ALK inhibitors, including alectinib, brigatinib, and lorlatinib, have extended disease control, particularly within the central nervous system. The introduction of antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan for HER2-mutant NSCLC, and emerging TKIs like zongertinib, represent new therapeutic milestones. Immunotherapy has become central to the management of both NSCLC and SCLC, with immune checkpoint inhibitors (ICIs) demonstrating unprecedented survival benefits. Beyond lung cancer, our group, in collaboration with Juntendo University ARO (academic research organization) and fifteen institutions in Japan, conducted the MARBLE phase II trial of atezolizumab plus chemotherapy for thymic carcinoma, achieving a 56% objective response rate and 9.6-month median progression-free survival, supporting potential ICI approval in Japan. Furthermore, novel immune strategies such as bispecific T-cell engagers (BiTEs) have shown promise. The DLL3-targeted BiTE tarlatamab significantly improved overall survival to 13.6 months in the phase III DeLLphi-304 trial for relapsed SCLC, with manageable cytokine release syndrome. Collectively, these advances signify a shift toward biologically driven, molecular-targeted or immune-integrated therapy, aiming to transform lung cancer into a chronic, manageable disease in the future, hopefully.
2026-05-28 | A phase II, single-arm trial of adebrelimab plus nab-paclitaxel and carboplatin as first-line therapy for advanced thymic carcinoma: Interim efficacy and safety results.
e20171 Background: Thymic carcinoma (TC) is a rare and aggressive malignancy with poor prognosis in advanced stages. Given the limited efficacy of standard first-line regimen (carboplatin/paclitaxel), there remains an urgent unmet need for novel treatment approaches. This study evaluated the efficacy and safety of the PD-L1 inhibitor adebrelimab in combination with nanoparticle albumin-bound (nab)-paclitaxel and carboplatin as first-line therapy for advanced or recurrent TC. Methods: Patients (pts) with unresectable UICC stage III or IV, recurrent, or metastatic TCs without any previous anti-tumor therapy were enrolled.During the induction phase, pts received adebrelimab (20 mg/kg) plus nab-paclitaxel (260 mg/m 2 ) and carboplatin (AUC 5) every 3 weeks for up to 4-6 cycles. This was followed by the maintenance phase, adebrelimab (20 mg/kg) every 3 weeks for up to 2 years (including the induction phase), until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR), and secondary endpoints included progression free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: Between August 15, 2023, and June 3, 2025, this study was conducted at two centers and enrolled a total of 37 pts. All pts were included in safety and efficacy analysis. The median age was 60.0 years old (range 29-71). A total of 26 pts (70.3%) pts completed the induction therapy and were transitioned to maintenance therapy while 11 pts (29.7%) remained on treatment at data cutoff (December 1, 2025). Four (10.8%) of 37 pts had complete response, 16 (43.2%) had partial response, and 17 (45.9%) had stable disease. The ORR was 54.1% (20/37) and DCR was 100% (37/37). The median PFS was 10.9 months (95% CI, 9.1-NA). Treatment-related adverse events (TRAEs) of any grade and of grade ≥3 severity occurred in 100% and 54.1% (20/37) of pts, respectively. The most common TRAEs were anemia, lymphocyte count decreased, and white blood cell count decreased. The immune-related AEs of grade ≥3 severity occurred in 16.2% (6/37) of pts, including immune-mediated rash, myositis and amylase increased. No grade 5 TRAEs were reported. Conclusions: Adebrelimab combined with nab-paclitaxel and carboplatin demonstrates promising efficacy and a manageable safety profile as first-line therapy for advanced or recurrent thymic carcinoma, offering a new potential treatment option for this patient population. Trial Registration: ChiCTR2300072705.
2026-05-22 | Clinicogenomic Landscape of MTAP-Deleted Thoracic Malignancies Across US and Japanese Nationwide Cohorts: Impact of Concurrent CDKN2A Alterations and Driver Mutations.
Methylthioadenosine phosphorylase (MTAP) deletion represents a promising therapeutic vulnerability through synthetic lethality. However, the clinical and molecular context of MTAP-deleted thoracic tumors, particularly with respect to actionable oncogenic drivers and immune checkpoint inhibitor efficacy, remains incompletely defined across diverse populations. We analyzed clinicogenomic data from two nationwide cohorts: AACR Project GENIE (United States; n = 11,091 evaluable samples) and Center for Cancer Genomics and Advanced Therapeutics (C-CAT; Japan; n = 4,851). MTAP copy number was assessed in lung, pleural, and thymic tumors. We evaluated histology-specific prevalence, comutational patterns, associations with actionable genomic alterations, tumor mutational burden (TMB), and overall survival (OS) in selected molecular subgroups. In lung cancer, MTAP deletion occurred at comparable frequencies between adenocarcinoma and squamous cell carcinoma within each cohort (GENIE: 8.1% v 9.8%; C-CAT: 19.6% v 16.5%) but was rare in small cell lung cancer (GENIE: 1.0%; C-CAT: 1.9%). In thymic tumors, MTAP deletion was observed predominantly in thymic carcinoma and was uncommon in thymoma. MTAP deletion was strongly associated with CDKN2A/B deletions and was rare in their absence. MTAP deletion frequently coexisted with actionable driver alterations, including EGFR mutations, ALK fusions, and ERBB2 alterations. A robust inverse association with RB1 mutations was observed in both cohorts. Although MTAP deletion appeared associated with lower TMB (P < .01) and shorter OS in EGFR-mutated lung cancer (median 18.5 v 31.4 months, P < .01), these associations were largely attributable to enrichment of oncogenic drivers and concurrent CDKN2A loss, respectively. MTAP-deleted thoracic tumors exhibit reproducible clinical and molecular features across populations. Our findings support the rational, globally applicable development of MTAP-targeted synthetic lethal strategies in thoracic malignancies, particularly in combination with molecular targeted agents.
2026-05-08 | Carboplatin plus pemetrexed versus pemetrexed alone in advanced thymoma and thymic carcinoma: a retrospective cohort study.
Pemetrexed is approved as a single agent for advanced and metastatic thymoma and thymic carcinoma. In practice, pemetrexed is often given with carboplatin, but the safety and effectiveness of this combination has not been established in either of these rare diseases. We identified patients with unresectable, recurrent, or metastatic thymoma or thymic carcinoma who were treated with carboplatin/pemetrexed or pemetrexed alone from 2006-2024. Time to disease progression and objective response were determined retrospectively using RECIST 1.1. Median progression-free survival (mPFS) and median overall survival (mOS) were estimated using Kaplan-Meier methodology. We identified 24 patients (14 thymoma; 10 thymic carcinoma), including 8 treated with carboplatin/pemetrexed and 16 with pemetrexed alone. For our combined cohort, mPFS was not reached (NR) with carboplatin/pemetrexed vs. 14.7m with pemetrexed (p=0.27). Among patients with thymoma, mPFS with carboplatin/pemetrexed was NR vs. 15.6m for pemetrexed (p=0.09), while among patients with thymic carcinoma mPFS was 10.9m vs. 14.7m (p=0.88), respectively. At a median follow-up of 49.0m (37m for carboplatin/pemetrexed; 107m for pemetrexed), mOS was NR across all groups. The objective response rate (ORR) was 1/8 (12.5%) vs. 5/16 (31%), and the disease control rate (DCR) was 7/8 (87.5%) vs. 11/16 (69%) with carboplatin/pemetrexed and pemetrexed respectively. Carboplatin/pemetrexed was well tolerated and not associated with statistically significant differences in PFS compared to pemetrexed monotherapy in our combined cohort or thymic carcinoma and thymoma subgroups. Carboplatin/pemetrexed demonstrated a numerically longer PFS with encouraging disease control rates particularly in patients with thymoma.
antibodies
2026-08-13 | Precision Oncology in Thymic Epithelial Tumors: Therapeutic Horizons and Implementation Barriers.
Thymic epithelial tumors (TETs), comprising thymomas and thymic carcinomas, are rare, biologically heterogeneous thoracic malignancies with limited therapeutic advances since platinum-based regimens were adopted decades ago. Recent genomic and immunophenotypic profiling has uncovered recurrent genomic alterations and high programmed death-ligand 1 (PD-L1) expression, particularly in thymic carcinoma, yet few targeted or immunotherapies have achieved regulatory approval. This mini-review synthesizes current knowledge on TET heterogeneity and the genomic landscape, evaluates the clinical evidence supporting targeted agents and immune checkpoint inhibitors, and examines emerging biomarkers, including circulating tumor DNA. We also address practical barriers to precision oncology in TETs: challenges of next-generation sequencing implementation and cost in resource-limited settings; scarcity of large, biomarker-driven trials; and safety concerns unique to TETs (immune-related toxicity). Finally, we discuss the translational hurdles for antibody-drug conjugates and cellular therapies, limited validated cell surface targets, antigen heterogeneity, and preclinical model gaps and outline strategic paths forward to enable rational, safe, and equitable precision therapeutics for TET patients.
2026-08-12 | Collision tumor of poorly differentiated thyroid carcinoma and intrathyroid thymic carcinoma arising in association with a branchial cleft-like cyst: a case report
Background Primary squamous carcinoma of the thyroid is an exceptionally rare malignancy, and its coexistence with poorly differentiated thyroid carcinoma (PDTC) is exceedingly uncommon. The pathogenesis of thyroid squamous carcinomas remains controversial, particularly when associated with congenital epithelial remnants such as branchial cleft-like cysts or thymic/ultimobranchial remnants. We report an unusual collision tumor composed of PDTC and intrathyroid thymic carcinoma (ITTC) arising in association with a longstanding cystic thyroid lesion. Case presentation A 59-year-old man initially presented with a left thyroid lesion that was interpreted as a benign branchial cleft cyst on ultrasound-guided fine-needle aspiration. After being lost to follow-up for more than four years, he re-presented with progressive enlargement of the lesion. Repeat cytology and core biopsy demonstrated a poorly differentiated carcinoma with squamous differentiation. Cross-sectional imaging revealed local invasion, retrosternal extension, and multiple bilateral pulmonary nodules suspicious for metastatic disease. Near total thyroidectomy was performed for symptomatic airway compression. Histopathological examination demonstrated two morphologically and immunophenotypically distinct malignant components: PDTC with solid, trabecular, and insular architecture, necrosis, increased mitotic activity, angioinvasion, lymphatic invasion, perineural invasion, and extrathyroidal extension; and a squamous carcinoma arising in association with a benign squamous-lined cyst. Immunohistochemically, the PDTC component expressed thyroglobulin, TTF-1, and PAX8, whereas the squamous component was positive for CK5/6, p63, and CD117 and negative for thyroid follicular markers, supporting ITTC. Outcome The final diagnosis was a collision tumor composed of PDTC and ITTC arising in association with a branchial cleft-like cyst or other embryologic cystic remnant. Although pulmonary biopsy and systemic treatment were planned, the patient developed severe bronchopneumonia and died before further staging could be completed. Conclusion This case illustrates an exceptionally rare collision tumor of the thyroid and highlights the diagnostic limitations of cytologic assessment in predominantly cystic lesions. It emphasizes the importance of repeat evaluation of enlarging cystic thyroid masses and comprehensive histopathological and immunohistochemical assessment for accurate diagnosis and appropriate clinical management.
2026-07-11 | Clinical and Immunologic Features of Primary Enteric-Type Thymic Adenocarcinomas: A Rare Variant of a Rare Cancer.
Primary thymic adenocarcinomas are a rare subtype of thymic carcinoma, which share morphologic and immunohistochemical features with gastrointestinal cancers. The immunologic features of thymic adenocarcinoma remain poorly understood, and optimal treatment strategies have not been established. In this single-institution retrospective study, we identified seven patients with enteric-type thymic adenocarcinoma. Clinical characteristics, histopathology, and molecular profiles were analyzed. Comprehensive immune profiling was conducted using peripheral blood mononuclear cells (PBMCs) and archival tumor tissue. The PBMC immune profiles were compared with those of non-adenocarcinoma thymic epithelial tumors and with samples obtained from healthy donors. Enteric-type thymic adenocarcinomas exhibit aggressive clinical behavior and respond poorly to systemic therapy, including immune checkpoint inhibitors. Genomic analyses revealed frequent TP53 mutations, a marker of poor prognosis for thymic epithelial tumors. Immune analyses in PBMCs revealed higher levels of effector T-cell subsets, including CD4+ and CD8+ T-cell subsets, and lower levels of immunosuppressive cell populations compared with other thymic epithelial tumors. Higher levels of serum analytes related to angiogenesis, cell proliferation, and growth were detected. Tumor immune profiling revealed features of an immune-desert phenotype. Enteric-type thymic adenocarcinomas are immunologically cold tumors that are enriched in peripheral immune markers reflective of cell proliferation and angiogenesis. The immunologic profile appears distinct from other thymic epithelial tumors and provides a potential explanation for the aggressive nature of this disease. If validated in other studies, these findings can potentially inform the development of optimal systemic therapies for this rare variant of thymic carcinoma.
2026-07-10 | Pathobiology of thymic epithelial tumours and the treatment strategy based on immuno-oncological characteristics: a narrative review.
Thymic epithelial tumours (TETs), including thymomas and thymic carcinomas, are relatively rare anterior mediastinal malignancies. Thymomas are well known to be associated with various autoimmune diseases, such as myasthenia gravis (MG), pure red cell aplasia, and hypogammaglobulinemia. The mainstay of treatment for all TETs is complete surgical resection, although recent advances in irradiation and anti-tumour drug therapies are increasingly indicated for advanced or recurrent disease. The pathobiology of TETs was reviewed to consider optimal treatment strategies based on their immuno-oncological characteristics. A comprehensive literature search was conducted using PubMed, focusing on the biology and treatment of TETs, along with integration of our original research data. Pathobiology is different between thymoma and thymic carcinoma. Incomplete T cell development is observed in thymoma, which may affect patient autoimmunity. Type AB, B1, and B2 thymomas harbour abundant immature T cells, which cannot act as effector T cells in treatment using immune checkpoint inhibitors (ICIs). Neoplastic thymic epithelial cells (TECs) express programmed cell death-ligand 1 (PD-L1) at varying levels, and frequent genetic aberrations are observed according to the World Health Organization (WHO) classification. Germinal centre formation in the surrounding thymus may have a clinical role in thymoma-associated MG. Regarding treatment strategies, radical minimally invasive thymectomy using robotic technology is now available for MG. Effective molecular-targeted and ICI therapies have recently been introduced, and further novel targeted therapies are currently under development. WHO histological subtypes and inflammatory biomarkers are practically useful for determining the treatment strategy. A fundamental understanding of pathobiology and immuno-oncology is crucial for the appropriate management of TETs.
2026-07-10 | Systemic therapy for advanced thymic epithelial tumors: a narrative review of current evidence and perspectives.
Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare tumors. Although systemic therapy is commonly used for unresectable advanced or recurrent TETs, establishing robust evidence remains challenging. This narrative review summarizes current evidence and incorporates the latest clinical trial data, reporting outcomes separately for thymoma and thymic carcinoma whenever possible. We also highlight practical considerations relevant to clinical practice, including dosing strategies and toxicity management. We searched PubMed and Google Scholar for prospective and retrospective original studies, meta-analyses, review articles, and case studies published up to November 2025 using terms including "thymoma", "thymic carcinoma", "thymic cancer", "thymic tumors", "thymic epithelial tumors", "chemotherapy", "systemic treatment", "immunotherapy", and "targeted therapy". Ongoing trials were identified via ClinicalTrials.gov and the Japan Registry of Clinical Trials. Retrospective studies enrolling fewer than 15 participants were excluded. Systemic therapy for advanced TETs continues to include cytotoxic chemotherapy as a major component. In selected settings, particularly in thymic carcinoma, targeted therapy and immune checkpoint inhibitors (ICIs) represent additional active options. Emerging trials suggest that combination strategies may enhance efficacy. Novel drugs, including bispecific antibodies and antibody-drug conjugates, are being evaluated in ongoing phase II trials. Despite the rarity of TETs, systemic treatment options have gradually expanded through the accumulation of evidence from small phase II studies. Future advances will require collaborative prospective trials to validate predictive biomarkers and support biomarker-enriched trial designs.
proteins
2025-12-10 | Circulating innate lymphoid cells and IL-18 as potential immune biomarkers in thymic tumors.
Thymic epithelial tumors (TETs) are rare malignancies frequently associated with autoimmunity. However, circulating immune biomarkers for patient stratification and disease monitoring remain undefined. Innate lymphoid cells (ILCs) are emerging regulators of tumor immunity, but their role in TETs has not yet been characterized. Peripheral blood samples from 32 patients with histologically confirmed TETs and 20 healthy donors were analyzed by multiparametric flow cytometry to quantify circulating ILC subsets. Serum cytokine concentrations were measured using multiplex immunoassays. Patients were stratified according to histology, disease activity, and presence of autoimmune manifestations. TETs displayed a significant expansion of circulating ILCs, mainly driven by an enrichment of ILC1, which was more pronounced in patients with active disease and in those with thymic carcinoma. Serum IL-18 levels were elevated-particularly in thymic carcinoma-and correlated with higher concentrations of type 2 cytokines (IL-4, IL-5, IL-9, IL-13). No concomitant increase in canonical ILC1 effector cytokines, including IFN-γ, was observed, indicating a functional dissociation between ILC1 expansion and their expected cytokine profile. These findings delineate a distinct systemic immune signature in TETs, characterized by IL-18 upregulation and altered ILC1 dynamics, with potential implications for immune regulation and autoimmunity. Circulating ILC profiling combined with IL-18 measurement may represent a promising approach for patient stratification, disease monitoring, and the development of novel immunomodulatory strategies in TETs.
2025-11-01 | 595 Preliminary results of safety and antitumor activity from a first-in-human phase 1 study of AWT020, a bifunctional anti-PD-1/IL-2 fusion protein, in patients with advanced tumors
2528 Background: Immune checkpoint inhibitors have transformed treatment landscape across multiple cancer types, however, resistance to anti-PD-(L)1 therapies remains a significant unmet medical need. AWT020 is a bifunctional fusion protein comprised of an anti-PD-1 antibody and a potency optimized IL-2. In preclinical studies, the mouse surrogate of AWT020 demonstrated superior antitumor activity compared to anti-mPD-1 alone or in combination with IL-2. These findings suggest that AWT020 monotherapy may benefit patients resistant to anti-PD-1 therapies. Methods: This first-in-human Phase 1 dose escalation study evaluates AWT020 monotherapy in adults with advanced or metastatic cancers who failed or were intolerant to standard therapies. The dose-escalation utilizes a Bayesian Optimal Interval design. Key endpoints include safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics, immunogenicity, and antitumor responses. Initial dose escalation results are presented herein. Clinical trial information: NCT06092580. Results: As of January 14, 2026, 41 patients received AWT020 at doses of 0.3, 0.6, and 1 mg/kg, including single-step (0.1 or 0.3 mg/kg) and two-step (0.1→0.3 mg/kg) priming regimens. Preliminary PK analysis showed approximately dose-proportional exposure. The majority of treatment-related adverse events (TRAEs) were low grade. The most frequently reported TRAEs were arthralgia (59%), rash (34%), fatigue (32%), and nausea (32%). Grade ≥3 TRAEs occurring in more than one subject included arthralgia (n=4), colitis (n=2), and thrombocytopenia (n=2). No patient experienced vascular leak syndrome. Among the 27 RECIST-evaluable patients, the overall response rate was 30%, and the disease control rate was 67%. Of the eight responders, five partial responders (thymic carcinoma, thymoma, clear cell renal cell carcinoma, neuroendocrine non-small cell lung cancer, and cholangiocarcinoma) had developed secondary resistance to anti-PD-(L)1 therapies. The remaining three responders were anti-PD-(L)1-naïve, including a cervical cancer patient who experienced confirmed complete response, and two partial responders with proficient mismatch repair (pMMR) tumors (adrenocortical carcinoma and uterine sarcoma). Ten additional patients with diverse cancer types achieved stable diseases, with tumor shrinkage observed in half of the patients, further supporting preliminary antitumor activity across broad tumor types. Conclusions: AWT020 demonstrates a manageable safety profile and promising early antitumor activity, including in patients with acquired resistance to anti-PD-(L)1 therapies and in patients with pMMR tumors which typically are unresponsive to immune monotherapy. Dose escalation is ongoing to establish MTD/RP2D. Clinical trial information: NCT06092580 .
2025-10-13 | Thymopentin Enhances Antitumor Immunity Through Thymic Rejuvenation and T Cell Functional Reprogramming
Background/Objectives: T cell dysfunction represents a fundamental barrier to effective cancer immunotherapy. Although immune checkpoint blockades and adoptive cell transfer have achieved clinical success, therapeutic resistance remains prevalent across cancer types. Thymopentin (TP5), a synthetic immunomodulatory pentapeptide (Arg-Lys-Asp-Val-Tyr), has demonstrated immunostimulatory properties, yet its anticancer potential remains unexplored. The aim of this study was to investigate TP5’s antitumor efficacy and underlying immunological mechanisms. Methods: We evaluated TP5’s therapeutic effects in multiple murine tumor models, including B16-F10 melanoma, MC38 colorectal carcinoma, Hepa 1-6, and LM3 hepatocellular carcinoma. Immune cell populations and functional states were characterized using flow cytometry, ELISAs, and immunofluorescence analyses. The potential of TP5 as an adjuvant for T cell-based therapies was also systematically assessed. Results: The TP5 treatment markedly suppressed tumor growth across caner models through strictly T cell-dependent mechanisms. Critically, TP5 promoted thymic rejuvenation under immunocompromised conditions, restoring the thymus–tumor immunological balance and revitalizing peripheral T cell immunity. TP5 functionally reprogrammed T cell states, preserving effector function while ameliorating exhaustion. Furthermore, TP5 demonstrated synergistic efficacy when combined with adoptive T cell therapies, enhancing both proliferation and effector functions. Conclusions: TP5 represents a promising immunomodulator that addresses fundamental limitations of current T cell therapies by simultaneously enhancing T cell function and reversing thymic involution under immunocompromised conditions. Our findings provide compelling evidence for TP5’s clinical translation in cancer treatment.
2025-05-28 | Combining SBRT with GM-CSF and peg-IFNα to induce abscopal effects in previously treated patients with stage IV thymic tumors: A single arm, single center, phase II trial.
8110 Background: After the failure of first-line treatment, patients with stage IV thymic tumors have a poor prognosis and few therapeutic options. Combining stereotactic body radiotherapy (SBRT) with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Pegylated interferon-α (Peg-IFNα) may induce abscopal effects and improve prognosis. Methods: We conducted this open-label, single-arm single center, phase Ⅱ trial to evaluate SBRT plus GM-CSF and Peg-IFNα in previously treated patients with stage Ⅳ thymic tumors. A 21-day treatment cycle consisted of SBRT delivered to one metastatic lesion with 30 Gy in 5 fractions from day 1, synchronous subcutaneous injection of GM-CSF 125 μg/ m 2 once daily for 14 days, and subcutaneous injection of Peg-IFNα 90 μg on day 8. If the patient has more than two metastatic lesions, another treatment cycle was repeated. After the completion of 1 or 2 treatment cycles, Peg-IFNα therapy was maintained for at least half a year with a subcutaneous injection of 90 μg once a month. The two primary endpoints were the proportion of patients with abscopal effects and the objective response rate (ORR). The secondary endpoints included overall survival (OS), progression-free survival (PFS), and therapeutic safety. Results: A total of 27 patients were enrolled in the trial from March 2021 to September 2024. One patient died of cardiac arrest before ORR evaluation during COVID-19 pandemic and was excluded, leaving 26 patients in the analysis, with 1 (3.8%) type A thymoma, 1 (3.8%) type AB thymoma,4 (15.4%) type B1 thymoma, 3 (11.5%) type B2 thymoma, 1 (3.8%) type B3 thymoma, 1 (3.8%) type B2+B3 thymoma, 13 (50.0%) thymic squamous cell carcinoma and 2 (7.7%) thymic neuroendocrine tumor. At a median follow-up of 26.4 months, 8 (30.8%) out of 26 patients had abscopal effects, and the ORR was 38.5%. The median OS for patients with abscopal effect has not been attained yet. The median PFS was 13.0 months. We observed that patients with abscopal effects tended to have longer OS and PFS than those without abscopal effects. 5 patients (19.2%) experienced Grade 3 treatment-related adverse events (CTCAE version 5.0). Conclusions: Combining SBRT with GM-CSF and Peg-IFNα was well tolerated with acceptable toxicity and may represent a promising salvage therapy for previously treated patients with stage IV thymic tumors. The occurrence of abscopal effects is likely to improve patient outcomes. Clinical trial information: NCT04517539 .
2025-05-28 | First-in-human study of AWT020, a bifunctional anti-PD-1/IL-2 fusion protein, in patients with advanced cancer.
e14500 Background: Whileimmune checkpoint inhibitors have become the standard of care for multiple cancer types, resistance to anti-PD-(L)1 therapies remains a significant unmet medical need. AWT020 is a bifunctional fusion protein comprised of an anti-PD-1 antibody and a potency optimized IL-2. Preclinical studies using a mouse surrogate have demonstrated superior antitumor activity compared to either anti-mPD-1 antibody alone or its combination with IL-2 in anti-PD-1 sensitive and resistant models. These findings suggest that AWT020 monotherapy has the potential to surpass standard anti-PD-1 therapies and provide a valuable treatment option for patients resistant to anti-PD-1 therapies. Methods: Study AWT020-001 (NCT06092580) is a first-in-human (FIH) trial evaluating AWT020 monotherapy (Q2W) in adults with advanced or metastatic cancers who have failed or were intolerant to standard therapies. The dose-escalation Phase 1 utilizes a Bayesian Optimal Interval design with a 28-day dose-limiting toxicity period. The primary objectives include assessing safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 (RP2D), and dosing interval. Secondary objectives include evaluating pharmacokinetics (PK), pharmacodynamic, immunogenicity, and antitumor response. Here, we present the initial results from the dose escalation phase. Results: As of January 8, 2025, 16 patients (8 males, 8 females) have been treated with AWT020 in three dose escalation groups (0.3, 0.6, and 1 mg/kg). Six patients received prior anti-PD-(L)1 therapies. Preliminary PK analysis indicates dose proportional properties of AWT020 within the 0.3 to 1 mg/kg dose range. Most treatment-related adverse events (TRAEs) were grades 1 to 2, including rash, arthralgia, hypothyroidism, nausea and fatigue. Grade ≥ 3 TRAEs included hypersensitivity reaction (Grade 4), hemoperitoneum, stomatitis, diabetes, worsening of rheumatoid arthritis, pain in extremity, and reactions related to infusion (cold sweat, arthralgia, backpain, chest pain, dysphonia, and dyspnoea). There was no evidence of vascular leak syndrome. Amongst the 12 patients with evaluable RECIST disease, two patients achieved partial response. One response occurred in a thymic carcinoma patient with primary resistance to anti-PD-1 therapy, and another was observed in a thymoma patient with acquired resistance to anti-PD-1 therapy. Six additional patients demonstrated disease stabilization, with three showing reductions in target lesions of 5%, 19% and 24%, further demonstrating antitumor activity. Conclusions: The initial data from this FIH study indicates that AWT020 has a manageable safety profile and is clinically active in cancers with primary or secondary resistance to anti-PD-1 therapies. The study is ongoing to optimize the dosing regimen and to establish MTD and RP2D. Clinical trial information: NCT06092580 .
cell therapies
2026-04-21 | Left brachiocephalic vein replacement and superior vena cava reconstruction with aortic homograft for thymic carcinoma.
Advanced intrathoracic tumours pose a significant challenge for thoracic surgeons because of the possible involvement of adjacent vital organs and major mediastinal vessels. The most effective therapeutic option for resectable thymic carcinomas is currently represented by complete surgical asportation en bloc with adjacent infiltrated structures to achieve more effective oncological outcomes. Vascular reconstruction, when required, is traditionally performed using prosthetic conduits; however, vascular homografts represent a potential alternative with several surgical and clinical advantages. We report a case of a large thymic carcinoma with mediastinal vessel invasion successfully treated by surgical resection and vascular reconstruction using an aortic homograft.
2026-04-03 | Abstract 3806: Development of a novel CAR T-cell therapy targeting thymic carcinoma
Abstract Introduction: Thymic carcinoma is a rare, highly aggressive mediastinal malignancy with limited effective therapies and considerable toxicity associated with immune checkpoint inhibitors. Although CAR T-cell therapy has revolutionized the treatment landscape for hematologic malignancies, its application to solid tumors, including thymic epithelial tumors, remains challenging due to disease rarity, a paucity of validated surface targets, and the risk of on-target, off-tumor autoimmune toxicity. In this study, we sought to address these barriers by characterizing antigen expression profiles across thymic carcinoma-relevant cell lines, engineering novel CAR constructs against prioritized candidate antigens, and evaluating antigen-specific cytotoxicity. These efforts aim to inform the development of next-generation cellular therapies tailored to the unique biology of this aggressive and understudied tumor type. Methods: Surface expression of TROP-2, c-KIT, and CD70 was quantified on candidate cell lines using flow cytometry. CAR T-cells were produced from healthy donor PBMCs via lentiviral transduction and expanded ex vivo. CAR expression was confirmed by detection of Fab fragments on CD3+ T cells. Antigen-specific cytotoxicity was evaluated in vitro using co-culture assays with selected antigen-positive cell lines, and target cell killing was quantified by 7-AAD staining and flow cytometric analysis. Results: Flow cytometry demonstrated robust surface expression of TROP-2 (83%), c-KIT (88%), and CD70 (99%) across the T1889, Kasumi, and U266 cell lines, respectively. Lentiviral transduction yielded CAR+ T cell populations of 48.2% (TROP-2), 24.7% (c-KIT), and 47.5% (CD70). All three constructs exhibited potent antigen-specific cytotoxicity substantially exceeding GFP+ CD3+ control T cells, confirming selective recognition and killing of target cells. These findings provide some of the first in vitro evidence supporting TROP-2, c-KIT, and CD70 as viable immunotherapeutic targets for thymic carcinoma and demonstrate effective CAR expression and selective cytotoxicity. This work establishes a foundation for rational multi-antigen CAR T cell design in a historically understudied solid tumor. Ongoing studies include FACS-based CAR enrichment, characterization of exhaustion markers, development of a dual-antigen synNotch CAR to mitigate off-tumor toxicity, and in vivo validation in murine models to support future clinical translation. Citation Format: Layla Ahmadi, Malak Khalifeh, Dimitar Donovski, DuyKhanh Pham Ceppa, Patrick Loehrer, Rohan Maniar, Huda Salman. Development of a novel CAR T-cell therapy targeting thymic carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3806.
2026-03-30 | Development of a Novel CAR T-Cell Therapy Targeting Thymic Carcinoma
Background Thymic carcinomas are rare anterior mediastinal malignancies with limited treatment options and modest responses to platinum-based chemotherapy. Immune checkpoint inhibitors have shown activity but often cause severe immune-related toxicities. Although CAR T-cell therapy has revolutionized hematologic cancer treatment, its application in thymic carcinoma is limited due to disease rarity, lack of tumor-specific surface antigens, and risks of on-target off-tumor toxicity, especially given the thymus’s role in immune tolerance. Recent studies have identified overexpression of TROP-2, c-KIT, and CD70 in thymic carcinoma, presenting novel therapeutic targets. Objectives Profile TROP-2, c-KIT, and CD70 surface expression on thymic carcinoma–relevant cell lines. Engineer CAR constructs targeting each antigen and validate CAR expression on T- cells. Evaluate antigen-specific cytotoxicity of CAR T-Cells in vitro to guide development of multi-antigen CAR T strategies. Methods Candidate cell lines were screened for surface expression of TROP-2, c-KIT, and CD70 using quantitative flow cytometry. CAR T-cells were generated from healthy donor PBMCs via lentiviral transduction and expanded ex vivo. Antigen-specific cytotoxicity was evaluated through in vitro coculture assays using selected patient-derived cell lines. Cytotoxic effects were quantified by 7-AAD via flow cytometry. Results Flow cytometry confirmed high surface expression of TROP-2 (83%), c-KIT (88%), and CD70 (99%) in T1889, Kasumi, and U266 cell lines, respectively. Lentiviral transduction produced Fab⁺ CAR-T populations of 48.2% (TROP-2), 24.7% (c-KIT), and 47.5% (CD70). All three CAR-T constructs showed antigen-specific cytotoxicity significantly greater than GFP⁺ CD3⁺ controls. Conclusions This study provides early in vitro evidence supporting CAR T-cell therapy targeting TROP-2, c- KIT, and CD70 for thymic carcinoma. Results confirm strong CAR expression and potent, selective killing of antigen-positive targets.
2022-10-17 | Upper thoracic empyema and concomitant superior vena cava syndrome treated with reconstructive surgery using a pedicled omental flap.
Superior vena cava (SVC) syndrome refers to a constellation of symptoms secondary to obstruction of blood flow through the SVC. In this condition, venous blood that usually drains into the SVC is diverted into the inferior vena cava (IVC) via collateral veins. Reconstructive surgery is challenging in such cases owing to the anomalous venous system. In this case report, we describe reconstructive surgery using a pedicled omental flap in a patient with upper thoracic empyema and concomitant SVC syndrome. A 68-year-old man underwent resection of malignant thymoma, the bilateral brachiocephalic veins, and a part of the right upper lobe, followed by polytetrafluoroethylene (PTFE) graft placement for venous system reconstruction, 2 years prior to presentation. He developed postoperative upper thoracic cavity empyema, which necessitated PTFE graft removal. Although the infection was controlled after 2 months, multiple right upper lobe pulmonary fistulas persisted, and the patient was referred to our department for further evaluation. Contrast-enhanced computed tomography revealed SVC syndrome characterized by SVC obstruction and consequent drainage of venous blood from the upper trunk into the IVC via collateral vessels. We debrided necrotic and infected tissues, and a pedicled omental flap was placed for upper lobe fistula coverage. The patient showed an uncomplicated postoperative course, and no recurrent empyema or pulmonary fistulas were observed 3 years postoperatively. Flaps associated with the SVC system show high venous pressures. The use of a pedicled omental flap was deemed feasible because this graft reaches the upper thorax even though it is associated with the IVC system.
2020-09-18 | Myasthenia Gravis Related to Thymic Carcinoma: A Case Study
Myasthenia gravis and thymoma are often presented in association with ∼10% of myasthenic cases having concomitant thymoma. Thymic carcinoma is one of the rarest/aggressive human epithelial tumors and has no correlation with myasthenia gravis hitherto. Here is provided a clinical case and review of literature on a very rare association of thymic carcinoma (with no sign of thymoma) and myasthenia gravis (antiacetylcholine receptor antibody positive). Two years after thymectomy, clinical evolution was satisfactory. This clinical case elicits hypothesis that thymic carcinoma may be related with myasthenia gravis, what may have good prognostic from oncologic and neurologic perspectives.
other
2024-09-26 | Characteristics of GTF2I L424H Mutated Thymoma and its Prognostic Impact: A Comprehensive Study
Thymic Epithelial Tumor (TET), a rare thoracic tumor, including thymoma and thymic carcinoma, has limited research on thymoma prognostic markers compared to thymic carcinoma. Using the cBiportal database, we analyzed gene expression, methylation, and mutation data in TETs. We explored the relationship between the GTF2I L424H mutation and thymoma pathology through differential gene expression, pathway enrichment analyses, and COX regression to develop a thymoma risk score. Compared with GTF2I wild-type, patients harboring GTF2I L424H mutation displayed distinctive gene expression and methylation profiles, resembling differences between pathology low-risk and high-risk patients. Importantly, patients with the GTF2I L424H mutation demonstrated a better prognosis than wild-type patients, but no such distinction was noted between low-risk and high-risk patients. Pathway analysis suggested that the mutation potentially regulates tumor development-related pathways, including the P53, Hippo, and TGFβ signaling pathways, ECM-receptor interaction, and tumor immune cell infiltration. Additionally, ten hub genes identified by cytoHubba, FGF20, FGF10, EGF, and TWIST1 were selected by stepwise multivariate Cox regression to construct a risk score model for thymoma. These findings highlight the potential role of the GTF2I L424H mutation as a prognostic factor, advocating for genetic profiling in personalized treatment strategies.
2024-05-01 | Long non-coding RNA LOXL1-AS1: a potential biomarker and therapeutic target in human malignant tumors.
Long non-coding RNAs (lncRNAs) are transcripts that contain more than 200 nucleotides. Despite their inability to code proteins, multiple studies have identified their important role in human cancer through different mechanisms. LncRNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1), a newly discovered lncRNA located on human chromosome 15q24.1, has recently been shown to be involved in the occurrence and progression of various malignancies, such as colorectal cancer, gastric cancer, hepatocellular carcinoma, prostate cancer, non-small cell lung cancer, ovarian cancer, cervical cancer, breast cancer, glioma, thymic carcinoma, pancreatic carcinoma. LOXL1-AS1 acts as competitive endogenous RNA (ceRNA) and via sponging various miRNAs, including miR-374b-5p, miR-21, miR-423-5p, miR-589-5p, miR-28-5p, miR-324-3p, miR-708-5p, miR-143-3p, miR-18b-5p, miR-761, miR-525-5p, miR-541-3p, miR-let-7a-5p, miR-3128, miR-3614-5p, miR-377-3p and miR-1224-5p to promote tumor cell proliferation, invasion, migration, apoptosis, cell cycle, and epithelial-mesenchymal transformation (EMT). In addition, LOXL1-AS1 is involved in the regulation of P13K/AKT and MAPK signaling pathways. This article reviews the current understanding of the biological function and clinical significance of LOXL1-AS1 in human cancers. These findings suggest that LOXL1-AS1 may be both a reliable biomarker and a potential therapeutic target for cancers.
2023-10-31 | 1214 IL-12 vectors engineered to encode a functional p35-p40 heterodimer or a single p35 subunit for cancer immunotherapy
Interleukin-12 (IL-12) is a 70-kDa heterodimeric cytokine composed of a 35 kDa(p35) and a 40 kDa subunit(p40). IL-12 has been proven to be a potent anticancer agent as it promotes the development of anti-tumor CD8+ T cells and NK cells. Although IL-12 has shown robust antitumor activity in preclinical studies and potent immune-stimulating potential in humans, there are no approved IL-12 therapeutic products due to its systemic toxicities. The IL-12 vectors described here are non-replicating MLV retrovectors which transduce rapidly dividing cells. Two types of IL-12 vectors were engineered. In the first type, both p35 and p40 are encoded for and linked by self-cleaving T2A peptide whereas in the second, only the p35 is encoded. The latter vector may be suitable for transducing tumor types that overexpress p40 such as squamous cell tumors.1 IL-12 tumor specificity can be achieved through local delivery of the vector, targeting via PiT2 receptors, the transduction and integration of rapidly dividing tumor cells, and/or pseudotyping the vector envelope to target tumor specific surface receptors. All IL-12 genes were synthesized at Genscript and the final plasmids were confirmed by whole plasmid sequencing at Primordium Labs. Human A375 melanoma cells were transduced by the first IL-12 vector and subjected to Western blotting to confirm the protein expression of the two subunits. Both human and murine IL-12 as well as human p35 vectors were produced and tested. An mIL-12 expressing mouse colorectal CT26 stable cell line was established. P40 subunit vector was also separately engineered and used to generate A375-P40 overexpressing cells. Functional IL-12(p70) was tested by mIL-12 or hIL-12 ELISAs and in vitro assays. The IL-12 vector encoding for the two subunits can successfully transduce mouse and human cancer cells which then express and secrete biologically functional IL-12. The other vector encoding for p35 only, when transducing a p40 expressing cell line, produces and secretes a fully functional p70(IL-12) as well. The data indicate the potential use of our IL-12 vectors as an efficient delivery system in IL-12 cancer gene therapy. Pre-clinical studies in a mouse tumor model of colorectal cancer demonstrate that IL-12 vector transduced tumors generate a significant immune response, inhibit tumor growth, and increase survival rate. Our current focus is the investigation of pseudotyped IL-12 vectors to target tumor specific surface receptors in in vivo tumor models. Karlin, et al. J Cancer Metastasis Treat, 2022;8:15, Review: Thymic carcinoma: review and update.
2022-04-22 | Long Non-Coding RNAs in the Cell Fate Determination of Neoplastic Thymic Epithelial Cells
Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine tumors that still require in-depth molecular characterization. Long non-coding RNAs (lncRNAs) are emerging as relevant gene expression modulators involved in the deregulation of several networks in almost all types of human cancer, including TETs. LncRNAs act at different control levels in the regulation of gene expression, from transcription to translation, and modulate several pathways relevant to cell fate determination under normal and pathological conditions. The activity of lncRNAs is strongly dependent on their expression, localization, and post-transcriptional modifications. Starting from our recently published studies, this review focuses on the involvement of lncRNAs in the acquisition of malignant traits by neoplastic thymic epithelial cells, and describes the possible use of these molecules as targets for the design of novel therapeutic approaches specific for TET. Furthermore, the involvement of lncRNAs in myasthenia gravis (MG)-related thymoma, which is still under investigation, is discussed.
2022-04-19 | Construction of immune-related LncRNAs classifier to predict prognosis and immunotherapy response in thymic epithelial tumors
The primary objective of this study was to construct an immune-related long noncoding RNAs (IRLs) classifier to precisely predict the prognosis and immunotherapy response of patients with thymic epithelial tumors (TET). Based on univariable Cox regression analysis and Lasso regression, six prognosis-related IRLs (AC004466.3, AC138207.2, AC148477.2, AL450270.1, HOXB-AS1 and SNHG8) were selected to build an IRL classifier. Importantly, results of qRT-PCR validated that higher expression levels of AC138207.2, AC148477.2, AL450270.1 and SNHG8 as well as lower expression levels of AC004466.3, and HOXB-AS1 in TETs samples compared with normal controls. The IRL classifier could effectively classify patients into the low-risk and high-risk groups based on the different survival parameters. In terms of predictive ability and clinical utility, the IRL classifier was superior to Masaoka staging system. Additionally, IRL classifier is significantly associated with immune cells infiltration (dendritic cells, activated CD4 memory T cells and tumor-infiltrating lymphocyte (TIL), T cell subsets in particular), immune microenvironment (immune score and immune checkpoint inhibitors) and immunogenicity (TMB) in TETs, which hints that IRL classifier is tightly correlated with immune characteristics and might guide more effective immunotherapy strategies for TETs patients. Encouragingly, according to TIDE algorithm, there were more immunotherapy responders in the low-risk IRL subgroup and the IRL score was robustly negatively linked to the immunotherapeutic response. To sum up, the IRL classifier was established, which can be used to predict the prognosis, immune infiltration status, immunotherapy response in TETs patients, and may facilitate personalized counseling for immunotherapy.
small molecules
2026-07-01 | 153P Efficacy and safety of lenvatinib in patients with thymic epithelial tumors: A retrospective, multicenter study
Thymic epithelial tumors (TETs) are rare malignancies with limited options after standard platinum-based chemotherapy. While the REMORA trial confirmed the efficacy of lenvatinib, a multi-targeted tyrosine kinase inhibitor (TKI), in thymic carcinoma (TC) patients with progressive disease, data for broader TET subtypes remain scarce. This study evaluated lenvatinib's efficacy and safety in patients with TETs, including TC and advanced malignant thymoma.
2026-05-29 | Advances in Pharmacological Treatment of Thoracic Malignancies.
Lung cancer remains the leading cause of cancer-related death worldwide, with over two million new cases annually. Advances in molecular biology and immuno-oncology have fundamentally transformed treatment strategies. Comprehensive genomic profiling has enabled precision medicine approaches, allowing the selection of targeted therapies based on driver alterations such as EGFR, ALK, and HER2. For EGFR-mutant NSCLC, sequential development of tyrosine kinase inhibitors (TKIs) from first- to third-generation agents-culminating in osimertinib-has markedly improved survival. Similarly, successive generations of ALK inhibitors, including alectinib, brigatinib, and lorlatinib, have extended disease control, particularly within the central nervous system. The introduction of antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan for HER2-mutant NSCLC, and emerging TKIs like zongertinib, represent new therapeutic milestones. Immunotherapy has become central to the management of both NSCLC and SCLC, with immune checkpoint inhibitors (ICIs) demonstrating unprecedented survival benefits. Beyond lung cancer, our group, in collaboration with Juntendo University ARO (academic research organization) and fifteen institutions in Japan, conducted the MARBLE phase II trial of atezolizumab plus chemotherapy for thymic carcinoma, achieving a 56% objective response rate and 9.6-month median progression-free survival, supporting potential ICI approval in Japan. Furthermore, novel immune strategies such as bispecific T-cell engagers (BiTEs) have shown promise. The DLL3-targeted BiTE tarlatamab significantly improved overall survival to 13.6 months in the phase III DeLLphi-304 trial for relapsed SCLC, with manageable cytokine release syndrome. Collectively, these advances signify a shift toward biologically driven, molecular-targeted or immune-integrated therapy, aiming to transform lung cancer into a chronic, manageable disease in the future, hopefully.
2026-05-28 | A phase II, single-arm trial of adebrelimab plus nab-paclitaxel and carboplatin as first-line therapy for advanced thymic carcinoma: Interim efficacy and safety results.
e20171 Background: Thymic carcinoma (TC) is a rare and aggressive malignancy with poor prognosis in advanced stages. Given the limited efficacy of standard first-line regimen (carboplatin/paclitaxel), there remains an urgent unmet need for novel treatment approaches. This study evaluated the efficacy and safety of the PD-L1 inhibitor adebrelimab in combination with nanoparticle albumin-bound (nab)-paclitaxel and carboplatin as first-line therapy for advanced or recurrent TC. Methods: Patients (pts) with unresectable UICC stage III or IV, recurrent, or metastatic TCs without any previous anti-tumor therapy were enrolled.During the induction phase, pts received adebrelimab (20 mg/kg) plus nab-paclitaxel (260 mg/m 2 ) and carboplatin (AUC 5) every 3 weeks for up to 4-6 cycles. This was followed by the maintenance phase, adebrelimab (20 mg/kg) every 3 weeks for up to 2 years (including the induction phase), until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR), and secondary endpoints included progression free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: Between August 15, 2023, and June 3, 2025, this study was conducted at two centers and enrolled a total of 37 pts. All pts were included in safety and efficacy analysis. The median age was 60.0 years old (range 29-71). A total of 26 pts (70.3%) pts completed the induction therapy and were transitioned to maintenance therapy while 11 pts (29.7%) remained on treatment at data cutoff (December 1, 2025). Four (10.8%) of 37 pts had complete response, 16 (43.2%) had partial response, and 17 (45.9%) had stable disease. The ORR was 54.1% (20/37) and DCR was 100% (37/37). The median PFS was 10.9 months (95% CI, 9.1-NA). Treatment-related adverse events (TRAEs) of any grade and of grade ≥3 severity occurred in 100% and 54.1% (20/37) of pts, respectively. The most common TRAEs were anemia, lymphocyte count decreased, and white blood cell count decreased. The immune-related AEs of grade ≥3 severity occurred in 16.2% (6/37) of pts, including immune-mediated rash, myositis and amylase increased. No grade 5 TRAEs were reported. Conclusions: Adebrelimab combined with nab-paclitaxel and carboplatin demonstrates promising efficacy and a manageable safety profile as first-line therapy for advanced or recurrent thymic carcinoma, offering a new potential treatment option for this patient population. Trial Registration: ChiCTR2300072705.
2026-05-22 | Clinicogenomic Landscape of MTAP-Deleted Thoracic Malignancies Across US and Japanese Nationwide Cohorts: Impact of Concurrent CDKN2A Alterations and Driver Mutations.
Methylthioadenosine phosphorylase (MTAP) deletion represents a promising therapeutic vulnerability through synthetic lethality. However, the clinical and molecular context of MTAP-deleted thoracic tumors, particularly with respect to actionable oncogenic drivers and immune checkpoint inhibitor efficacy, remains incompletely defined across diverse populations. We analyzed clinicogenomic data from two nationwide cohorts: AACR Project GENIE (United States; n = 11,091 evaluable samples) and Center for Cancer Genomics and Advanced Therapeutics (C-CAT; Japan; n = 4,851). MTAP copy number was assessed in lung, pleural, and thymic tumors. We evaluated histology-specific prevalence, comutational patterns, associations with actionable genomic alterations, tumor mutational burden (TMB), and overall survival (OS) in selected molecular subgroups. In lung cancer, MTAP deletion occurred at comparable frequencies between adenocarcinoma and squamous cell carcinoma within each cohort (GENIE: 8.1% v 9.8%; C-CAT: 19.6% v 16.5%) but was rare in small cell lung cancer (GENIE: 1.0%; C-CAT: 1.9%). In thymic tumors, MTAP deletion was observed predominantly in thymic carcinoma and was uncommon in thymoma. MTAP deletion was strongly associated with CDKN2A/B deletions and was rare in their absence. MTAP deletion frequently coexisted with actionable driver alterations, including EGFR mutations, ALK fusions, and ERBB2 alterations. A robust inverse association with RB1 mutations was observed in both cohorts. Although MTAP deletion appeared associated with lower TMB (P < .01) and shorter OS in EGFR-mutated lung cancer (median 18.5 v 31.4 months, P < .01), these associations were largely attributable to enrichment of oncogenic drivers and concurrent CDKN2A loss, respectively. MTAP-deleted thoracic tumors exhibit reproducible clinical and molecular features across populations. Our findings support the rational, globally applicable development of MTAP-targeted synthetic lethal strategies in thoracic malignancies, particularly in combination with molecular targeted agents.
2026-05-08 | Carboplatin plus pemetrexed versus pemetrexed alone in advanced thymoma and thymic carcinoma: a retrospective cohort study.
Pemetrexed is approved as a single agent for advanced and metastatic thymoma and thymic carcinoma. In practice, pemetrexed is often given with carboplatin, but the safety and effectiveness of this combination has not been established in either of these rare diseases. We identified patients with unresectable, recurrent, or metastatic thymoma or thymic carcinoma who were treated with carboplatin/pemetrexed or pemetrexed alone from 2006-2024. Time to disease progression and objective response were determined retrospectively using RECIST 1.1. Median progression-free survival (mPFS) and median overall survival (mOS) were estimated using Kaplan-Meier methodology. We identified 24 patients (14 thymoma; 10 thymic carcinoma), including 8 treated with carboplatin/pemetrexed and 16 with pemetrexed alone. For our combined cohort, mPFS was not reached (NR) with carboplatin/pemetrexed vs. 14.7m with pemetrexed (p=0.27). Among patients with thymoma, mPFS with carboplatin/pemetrexed was NR vs. 15.6m for pemetrexed (p=0.09), while among patients with thymic carcinoma mPFS was 10.9m vs. 14.7m (p=0.88), respectively. At a median follow-up of 49.0m (37m for carboplatin/pemetrexed; 107m for pemetrexed), mOS was NR across all groups. The objective response rate (ORR) was 1/8 (12.5%) vs. 5/16 (31%), and the disease control rate (DCR) was 7/8 (87.5%) vs. 11/16 (69%) with carboplatin/pemetrexed and pemetrexed respectively. Carboplatin/pemetrexed was well tolerated and not associated with statistically significant differences in PFS compared to pemetrexed monotherapy in our combined cohort or thymic carcinoma and thymoma subgroups. Carboplatin/pemetrexed demonstrated a numerically longer PFS with encouraging disease control rates particularly in patients with thymoma.
antibodies
2026-08-13 | Precision Oncology in Thymic Epithelial Tumors: Therapeutic Horizons and Implementation Barriers.
Thymic epithelial tumors (TETs), comprising thymomas and thymic carcinomas, are rare, biologically heterogeneous thoracic malignancies with limited therapeutic advances since platinum-based regimens were adopted decades ago. Recent genomic and immunophenotypic profiling has uncovered recurrent genomic alterations and high programmed death-ligand 1 (PD-L1) expression, particularly in thymic carcinoma, yet few targeted or immunotherapies have achieved regulatory approval. This mini-review synthesizes current knowledge on TET heterogeneity and the genomic landscape, evaluates the clinical evidence supporting targeted agents and immune checkpoint inhibitors, and examines emerging biomarkers, including circulating tumor DNA. We also address practical barriers to precision oncology in TETs: challenges of next-generation sequencing implementation and cost in resource-limited settings; scarcity of large, biomarker-driven trials; and safety concerns unique to TETs (immune-related toxicity). Finally, we discuss the translational hurdles for antibody-drug conjugates and cellular therapies, limited validated cell surface targets, antigen heterogeneity, and preclinical model gaps and outline strategic paths forward to enable rational, safe, and equitable precision therapeutics for TET patients.
2026-08-12 | Collision tumor of poorly differentiated thyroid carcinoma and intrathyroid thymic carcinoma arising in association with a branchial cleft-like cyst: a case report
Background Primary squamous carcinoma of the thyroid is an exceptionally rare malignancy, and its coexistence with poorly differentiated thyroid carcinoma (PDTC) is exceedingly uncommon. The pathogenesis of thyroid squamous carcinomas remains controversial, particularly when associated with congenital epithelial remnants such as branchial cleft-like cysts or thymic/ultimobranchial remnants. We report an unusual collision tumor composed of PDTC and intrathyroid thymic carcinoma (ITTC) arising in association with a longstanding cystic thyroid lesion. Case presentation A 59-year-old man initially presented with a left thyroid lesion that was interpreted as a benign branchial cleft cyst on ultrasound-guided fine-needle aspiration. After being lost to follow-up for more than four years, he re-presented with progressive enlargement of the lesion. Repeat cytology and core biopsy demonstrated a poorly differentiated carcinoma with squamous differentiation. Cross-sectional imaging revealed local invasion, retrosternal extension, and multiple bilateral pulmonary nodules suspicious for metastatic disease. Near total thyroidectomy was performed for symptomatic airway compression. Histopathological examination demonstrated two morphologically and immunophenotypically distinct malignant components: PDTC with solid, trabecular, and insular architecture, necrosis, increased mitotic activity, angioinvasion, lymphatic invasion, perineural invasion, and extrathyroidal extension; and a squamous carcinoma arising in association with a benign squamous-lined cyst. Immunohistochemically, the PDTC component expressed thyroglobulin, TTF-1, and PAX8, whereas the squamous component was positive for CK5/6, p63, and CD117 and negative for thyroid follicular markers, supporting ITTC. Outcome The final diagnosis was a collision tumor composed of PDTC and ITTC arising in association with a branchial cleft-like cyst or other embryologic cystic remnant. Although pulmonary biopsy and systemic treatment were planned, the patient developed severe bronchopneumonia and died before further staging could be completed. Conclusion This case illustrates an exceptionally rare collision tumor of the thyroid and highlights the diagnostic limitations of cytologic assessment in predominantly cystic lesions. It emphasizes the importance of repeat evaluation of enlarging cystic thyroid masses and comprehensive histopathological and immunohistochemical assessment for accurate diagnosis and appropriate clinical management.
2026-07-11 | Clinical and Immunologic Features of Primary Enteric-Type Thymic Adenocarcinomas: A Rare Variant of a Rare Cancer.
Primary thymic adenocarcinomas are a rare subtype of thymic carcinoma, which share morphologic and immunohistochemical features with gastrointestinal cancers. The immunologic features of thymic adenocarcinoma remain poorly understood, and optimal treatment strategies have not been established. In this single-institution retrospective study, we identified seven patients with enteric-type thymic adenocarcinoma. Clinical characteristics, histopathology, and molecular profiles were analyzed. Comprehensive immune profiling was conducted using peripheral blood mononuclear cells (PBMCs) and archival tumor tissue. The PBMC immune profiles were compared with those of non-adenocarcinoma thymic epithelial tumors and with samples obtained from healthy donors. Enteric-type thymic adenocarcinomas exhibit aggressive clinical behavior and respond poorly to systemic therapy, including immune checkpoint inhibitors. Genomic analyses revealed frequent TP53 mutations, a marker of poor prognosis for thymic epithelial tumors. Immune analyses in PBMCs revealed higher levels of effector T-cell subsets, including CD4+ and CD8+ T-cell subsets, and lower levels of immunosuppressive cell populations compared with other thymic epithelial tumors. Higher levels of serum analytes related to angiogenesis, cell proliferation, and growth were detected. Tumor immune profiling revealed features of an immune-desert phenotype. Enteric-type thymic adenocarcinomas are immunologically cold tumors that are enriched in peripheral immune markers reflective of cell proliferation and angiogenesis. The immunologic profile appears distinct from other thymic epithelial tumors and provides a potential explanation for the aggressive nature of this disease. If validated in other studies, these findings can potentially inform the development of optimal systemic therapies for this rare variant of thymic carcinoma.
2026-07-10 | Pathobiology of thymic epithelial tumours and the treatment strategy based on immuno-oncological characteristics: a narrative review.
Thymic epithelial tumours (TETs), including thymomas and thymic carcinomas, are relatively rare anterior mediastinal malignancies. Thymomas are well known to be associated with various autoimmune diseases, such as myasthenia gravis (MG), pure red cell aplasia, and hypogammaglobulinemia. The mainstay of treatment for all TETs is complete surgical resection, although recent advances in irradiation and anti-tumour drug therapies are increasingly indicated for advanced or recurrent disease. The pathobiology of TETs was reviewed to consider optimal treatment strategies based on their immuno-oncological characteristics. A comprehensive literature search was conducted using PubMed, focusing on the biology and treatment of TETs, along with integration of our original research data. Pathobiology is different between thymoma and thymic carcinoma. Incomplete T cell development is observed in thymoma, which may affect patient autoimmunity. Type AB, B1, and B2 thymomas harbour abundant immature T cells, which cannot act as effector T cells in treatment using immune checkpoint inhibitors (ICIs). Neoplastic thymic epithelial cells (TECs) express programmed cell death-ligand 1 (PD-L1) at varying levels, and frequent genetic aberrations are observed according to the World Health Organization (WHO) classification. Germinal centre formation in the surrounding thymus may have a clinical role in thymoma-associated MG. Regarding treatment strategies, radical minimally invasive thymectomy using robotic technology is now available for MG. Effective molecular-targeted and ICI therapies have recently been introduced, and further novel targeted therapies are currently under development. WHO histological subtypes and inflammatory biomarkers are practically useful for determining the treatment strategy. A fundamental understanding of pathobiology and immuno-oncology is crucial for the appropriate management of TETs.
2026-07-10 | Systemic therapy for advanced thymic epithelial tumors: a narrative review of current evidence and perspectives.
Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare tumors. Although systemic therapy is commonly used for unresectable advanced or recurrent TETs, establishing robust evidence remains challenging. This narrative review summarizes current evidence and incorporates the latest clinical trial data, reporting outcomes separately for thymoma and thymic carcinoma whenever possible. We also highlight practical considerations relevant to clinical practice, including dosing strategies and toxicity management. We searched PubMed and Google Scholar for prospective and retrospective original studies, meta-analyses, review articles, and case studies published up to November 2025 using terms including "thymoma", "thymic carcinoma", "thymic cancer", "thymic tumors", "thymic epithelial tumors", "chemotherapy", "systemic treatment", "immunotherapy", and "targeted therapy". Ongoing trials were identified via ClinicalTrials.gov and the Japan Registry of Clinical Trials. Retrospective studies enrolling fewer than 15 participants were excluded. Systemic therapy for advanced TETs continues to include cytotoxic chemotherapy as a major component. In selected settings, particularly in thymic carcinoma, targeted therapy and immune checkpoint inhibitors (ICIs) represent additional active options. Emerging trials suggest that combination strategies may enhance efficacy. Novel drugs, including bispecific antibodies and antibody-drug conjugates, are being evaluated in ongoing phase II trials. Despite the rarity of TETs, systemic treatment options have gradually expanded through the accumulation of evidence from small phase II studies. Future advances will require collaborative prospective trials to validate predictive biomarkers and support biomarker-enriched trial designs.
proteins
2025-12-10 | Circulating innate lymphoid cells and IL-18 as potential immune biomarkers in thymic tumors.
Thymic epithelial tumors (TETs) are rare malignancies frequently associated with autoimmunity. However, circulating immune biomarkers for patient stratification and disease monitoring remain undefined. Innate lymphoid cells (ILCs) are emerging regulators of tumor immunity, but their role in TETs has not yet been characterized. Peripheral blood samples from 32 patients with histologically confirmed TETs and 20 healthy donors were analyzed by multiparametric flow cytometry to quantify circulating ILC subsets. Serum cytokine concentrations were measured using multiplex immunoassays. Patients were stratified according to histology, disease activity, and presence of autoimmune manifestations. TETs displayed a significant expansion of circulating ILCs, mainly driven by an enrichment of ILC1, which was more pronounced in patients with active disease and in those with thymic carcinoma. Serum IL-18 levels were elevated-particularly in thymic carcinoma-and correlated with higher concentrations of type 2 cytokines (IL-4, IL-5, IL-9, IL-13). No concomitant increase in canonical ILC1 effector cytokines, including IFN-γ, was observed, indicating a functional dissociation between ILC1 expansion and their expected cytokine profile. These findings delineate a distinct systemic immune signature in TETs, characterized by IL-18 upregulation and altered ILC1 dynamics, with potential implications for immune regulation and autoimmunity. Circulating ILC profiling combined with IL-18 measurement may represent a promising approach for patient stratification, disease monitoring, and the development of novel immunomodulatory strategies in TETs.
2025-11-01 | 595 Preliminary results of safety and antitumor activity from a first-in-human phase 1 study of AWT020, a bifunctional anti-PD-1/IL-2 fusion protein, in patients with advanced tumors
2528 Background: Immune checkpoint inhibitors have transformed treatment landscape across multiple cancer types, however, resistance to anti-PD-(L)1 therapies remains a significant unmet medical need. AWT020 is a bifunctional fusion protein comprised of an anti-PD-1 antibody and a potency optimized IL-2. In preclinical studies, the mouse surrogate of AWT020 demonstrated superior antitumor activity compared to anti-mPD-1 alone or in combination with IL-2. These findings suggest that AWT020 monotherapy may benefit patients resistant to anti-PD-1 therapies. Methods: This first-in-human Phase 1 dose escalation study evaluates AWT020 monotherapy in adults with advanced or metastatic cancers who failed or were intolerant to standard therapies. The dose-escalation utilizes a Bayesian Optimal Interval design. Key endpoints include safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics, immunogenicity, and antitumor responses. Initial dose escalation results are presented herein. Clinical trial information: NCT06092580. Results: As of January 14, 2026, 41 patients received AWT020 at doses of 0.3, 0.6, and 1 mg/kg, including single-step (0.1 or 0.3 mg/kg) and two-step (0.1→0.3 mg/kg) priming regimens. Preliminary PK analysis showed approximately dose-proportional exposure. The majority of treatment-related adverse events (TRAEs) were low grade. The most frequently reported TRAEs were arthralgia (59%), rash (34%), fatigue (32%), and nausea (32%). Grade ≥3 TRAEs occurring in more than one subject included arthralgia (n=4), colitis (n=2), and thrombocytopenia (n=2). No patient experienced vascular leak syndrome. Among the 27 RECIST-evaluable patients, the overall response rate was 30%, and the disease control rate was 67%. Of the eight responders, five partial responders (thymic carcinoma, thymoma, clear cell renal cell carcinoma, neuroendocrine non-small cell lung cancer, and cholangiocarcinoma) had developed secondary resistance to anti-PD-(L)1 therapies. The remaining three responders were anti-PD-(L)1-naïve, including a cervical cancer patient who experienced confirmed complete response, and two partial responders with proficient mismatch repair (pMMR) tumors (adrenocortical carcinoma and uterine sarcoma). Ten additional patients with diverse cancer types achieved stable diseases, with tumor shrinkage observed in half of the patients, further supporting preliminary antitumor activity across broad tumor types. Conclusions: AWT020 demonstrates a manageable safety profile and promising early antitumor activity, including in patients with acquired resistance to anti-PD-(L)1 therapies and in patients with pMMR tumors which typically are unresponsive to immune monotherapy. Dose escalation is ongoing to establish MTD/RP2D. Clinical trial information: NCT06092580 .
2025-10-13 | Thymopentin Enhances Antitumor Immunity Through Thymic Rejuvenation and T Cell Functional Reprogramming
Background/Objectives: T cell dysfunction represents a fundamental barrier to effective cancer immunotherapy. Although immune checkpoint blockades and adoptive cell transfer have achieved clinical success, therapeutic resistance remains prevalent across cancer types. Thymopentin (TP5), a synthetic immunomodulatory pentapeptide (Arg-Lys-Asp-Val-Tyr), has demonstrated immunostimulatory properties, yet its anticancer potential remains unexplored. The aim of this study was to investigate TP5’s antitumor efficacy and underlying immunological mechanisms. Methods: We evaluated TP5’s therapeutic effects in multiple murine tumor models, including B16-F10 melanoma, MC38 colorectal carcinoma, Hepa 1-6, and LM3 hepatocellular carcinoma. Immune cell populations and functional states were characterized using flow cytometry, ELISAs, and immunofluorescence analyses. The potential of TP5 as an adjuvant for T cell-based therapies was also systematically assessed. Results: The TP5 treatment markedly suppressed tumor growth across caner models through strictly T cell-dependent mechanisms. Critically, TP5 promoted thymic rejuvenation under immunocompromised conditions, restoring the thymus–tumor immunological balance and revitalizing peripheral T cell immunity. TP5 functionally reprogrammed T cell states, preserving effector function while ameliorating exhaustion. Furthermore, TP5 demonstrated synergistic efficacy when combined with adoptive T cell therapies, enhancing both proliferation and effector functions. Conclusions: TP5 represents a promising immunomodulator that addresses fundamental limitations of current T cell therapies by simultaneously enhancing T cell function and reversing thymic involution under immunocompromised conditions. Our findings provide compelling evidence for TP5’s clinical translation in cancer treatment.
2025-05-28 | Combining SBRT with GM-CSF and peg-IFNα to induce abscopal effects in previously treated patients with stage IV thymic tumors: A single arm, single center, phase II trial.
8110 Background: After the failure of first-line treatment, patients with stage IV thymic tumors have a poor prognosis and few therapeutic options. Combining stereotactic body radiotherapy (SBRT) with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Pegylated interferon-α (Peg-IFNα) may induce abscopal effects and improve prognosis. Methods: We conducted this open-label, single-arm single center, phase Ⅱ trial to evaluate SBRT plus GM-CSF and Peg-IFNα in previously treated patients with stage Ⅳ thymic tumors. A 21-day treatment cycle consisted of SBRT delivered to one metastatic lesion with 30 Gy in 5 fractions from day 1, synchronous subcutaneous injection of GM-CSF 125 μg/ m 2 once daily for 14 days, and subcutaneous injection of Peg-IFNα 90 μg on day 8. If the patient has more than two metastatic lesions, another treatment cycle was repeated. After the completion of 1 or 2 treatment cycles, Peg-IFNα therapy was maintained for at least half a year with a subcutaneous injection of 90 μg once a month. The two primary endpoints were the proportion of patients with abscopal effects and the objective response rate (ORR). The secondary endpoints included overall survival (OS), progression-free survival (PFS), and therapeutic safety. Results: A total of 27 patients were enrolled in the trial from March 2021 to September 2024. One patient died of cardiac arrest before ORR evaluation during COVID-19 pandemic and was excluded, leaving 26 patients in the analysis, with 1 (3.8%) type A thymoma, 1 (3.8%) type AB thymoma,4 (15.4%) type B1 thymoma, 3 (11.5%) type B2 thymoma, 1 (3.8%) type B3 thymoma, 1 (3.8%) type B2+B3 thymoma, 13 (50.0%) thymic squamous cell carcinoma and 2 (7.7%) thymic neuroendocrine tumor. At a median follow-up of 26.4 months, 8 (30.8%) out of 26 patients had abscopal effects, and the ORR was 38.5%. The median OS for patients with abscopal effect has not been attained yet. The median PFS was 13.0 months. We observed that patients with abscopal effects tended to have longer OS and PFS than those without abscopal effects. 5 patients (19.2%) experienced Grade 3 treatment-related adverse events (CTCAE version 5.0). Conclusions: Combining SBRT with GM-CSF and Peg-IFNα was well tolerated with acceptable toxicity and may represent a promising salvage therapy for previously treated patients with stage IV thymic tumors. The occurrence of abscopal effects is likely to improve patient outcomes. Clinical trial information: NCT04517539 .
2025-05-28 | First-in-human study of AWT020, a bifunctional anti-PD-1/IL-2 fusion protein, in patients with advanced cancer.
e14500 Background: Whileimmune checkpoint inhibitors have become the standard of care for multiple cancer types, resistance to anti-PD-(L)1 therapies remains a significant unmet medical need. AWT020 is a bifunctional fusion protein comprised of an anti-PD-1 antibody and a potency optimized IL-2. Preclinical studies using a mouse surrogate have demonstrated superior antitumor activity compared to either anti-mPD-1 antibody alone or its combination with IL-2 in anti-PD-1 sensitive and resistant models. These findings suggest that AWT020 monotherapy has the potential to surpass standard anti-PD-1 therapies and provide a valuable treatment option for patients resistant to anti-PD-1 therapies. Methods: Study AWT020-001 (NCT06092580) is a first-in-human (FIH) trial evaluating AWT020 monotherapy (Q2W) in adults with advanced or metastatic cancers who have failed or were intolerant to standard therapies. The dose-escalation Phase 1 utilizes a Bayesian Optimal Interval design with a 28-day dose-limiting toxicity period. The primary objectives include assessing safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 (RP2D), and dosing interval. Secondary objectives include evaluating pharmacokinetics (PK), pharmacodynamic, immunogenicity, and antitumor response. Here, we present the initial results from the dose escalation phase. Results: As of January 8, 2025, 16 patients (8 males, 8 females) have been treated with AWT020 in three dose escalation groups (0.3, 0.6, and 1 mg/kg). Six patients received prior anti-PD-(L)1 therapies. Preliminary PK analysis indicates dose proportional properties of AWT020 within the 0.3 to 1 mg/kg dose range. Most treatment-related adverse events (TRAEs) were grades 1 to 2, including rash, arthralgia, hypothyroidism, nausea and fatigue. Grade ≥ 3 TRAEs included hypersensitivity reaction (Grade 4), hemoperitoneum, stomatitis, diabetes, worsening of rheumatoid arthritis, pain in extremity, and reactions related to infusion (cold sweat, arthralgia, backpain, chest pain, dysphonia, and dyspnoea). There was no evidence of vascular leak syndrome. Amongst the 12 patients with evaluable RECIST disease, two patients achieved partial response. One response occurred in a thymic carcinoma patient with primary resistance to anti-PD-1 therapy, and another was observed in a thymoma patient with acquired resistance to anti-PD-1 therapy. Six additional patients demonstrated disease stabilization, with three showing reductions in target lesions of 5%, 19% and 24%, further demonstrating antitumor activity. Conclusions: The initial data from this FIH study indicates that AWT020 has a manageable safety profile and is clinically active in cancers with primary or secondary resistance to anti-PD-1 therapies. The study is ongoing to optimize the dosing regimen and to establish MTD and RP2D. Clinical trial information: NCT06092580 .
cell therapies
2026-04-21 | Left brachiocephalic vein replacement and superior vena cava reconstruction with aortic homograft for thymic carcinoma.
Advanced intrathoracic tumours pose a significant challenge for thoracic surgeons because of the possible involvement of adjacent vital organs and major mediastinal vessels. The most effective therapeutic option for resectable thymic carcinomas is currently represented by complete surgical asportation en bloc with adjacent infiltrated structures to achieve more effective oncological outcomes. Vascular reconstruction, when required, is traditionally performed using prosthetic conduits; however, vascular homografts represent a potential alternative with several surgical and clinical advantages. We report a case of a large thymic carcinoma with mediastinal vessel invasion successfully treated by surgical resection and vascular reconstruction using an aortic homograft.
2026-04-03 | Abstract 3806: Development of a novel CAR T-cell therapy targeting thymic carcinoma
Abstract Introduction: Thymic carcinoma is a rare, highly aggressive mediastinal malignancy with limited effective therapies and considerable toxicity associated with immune checkpoint inhibitors. Although CAR T-cell therapy has revolutionized the treatment landscape for hematologic malignancies, its application to solid tumors, including thymic epithelial tumors, remains challenging due to disease rarity, a paucity of validated surface targets, and the risk of on-target, off-tumor autoimmune toxicity. In this study, we sought to address these barriers by characterizing antigen expression profiles across thymic carcinoma-relevant cell lines, engineering novel CAR constructs against prioritized candidate antigens, and evaluating antigen-specific cytotoxicity. These efforts aim to inform the development of next-generation cellular therapies tailored to the unique biology of this aggressive and understudied tumor type. Methods: Surface expression of TROP-2, c-KIT, and CD70 was quantified on candidate cell lines using flow cytometry. CAR T-cells were produced from healthy donor PBMCs via lentiviral transduction and expanded ex vivo. CAR expression was confirmed by detection of Fab fragments on CD3+ T cells. Antigen-specific cytotoxicity was evaluated in vitro using co-culture assays with selected antigen-positive cell lines, and target cell killing was quantified by 7-AAD staining and flow cytometric analysis. Results: Flow cytometry demonstrated robust surface expression of TROP-2 (83%), c-KIT (88%), and CD70 (99%) across the T1889, Kasumi, and U266 cell lines, respectively. Lentiviral transduction yielded CAR+ T cell populations of 48.2% (TROP-2), 24.7% (c-KIT), and 47.5% (CD70). All three constructs exhibited potent antigen-specific cytotoxicity substantially exceeding GFP+ CD3+ control T cells, confirming selective recognition and killing of target cells. These findings provide some of the first in vitro evidence supporting TROP-2, c-KIT, and CD70 as viable immunotherapeutic targets for thymic carcinoma and demonstrate effective CAR expression and selective cytotoxicity. This work establishes a foundation for rational multi-antigen CAR T cell design in a historically understudied solid tumor. Ongoing studies include FACS-based CAR enrichment, characterization of exhaustion markers, development of a dual-antigen synNotch CAR to mitigate off-tumor toxicity, and in vivo validation in murine models to support future clinical translation. Citation Format: Layla Ahmadi, Malak Khalifeh, Dimitar Donovski, DuyKhanh Pham Ceppa, Patrick Loehrer, Rohan Maniar, Huda Salman. Development of a novel CAR T-cell therapy targeting thymic carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3806.
2026-03-30 | Development of a Novel CAR T-Cell Therapy Targeting Thymic Carcinoma
Background Thymic carcinomas are rare anterior mediastinal malignancies with limited treatment options and modest responses to platinum-based chemotherapy. Immune checkpoint inhibitors have shown activity but often cause severe immune-related toxicities. Although CAR T-cell therapy has revolutionized hematologic cancer treatment, its application in thymic carcinoma is limited due to disease rarity, lack of tumor-specific surface antigens, and risks of on-target off-tumor toxicity, especially given the thymus’s role in immune tolerance. Recent studies have identified overexpression of TROP-2, c-KIT, and CD70 in thymic carcinoma, presenting novel therapeutic targets. Objectives Profile TROP-2, c-KIT, and CD70 surface expression on thymic carcinoma–relevant cell lines. Engineer CAR constructs targeting each antigen and validate CAR expression on T- cells. Evaluate antigen-specific cytotoxicity of CAR T-Cells in vitro to guide development of multi-antigen CAR T strategies. Methods Candidate cell lines were screened for surface expression of TROP-2, c-KIT, and CD70 using quantitative flow cytometry. CAR T-cells were generated from healthy donor PBMCs via lentiviral transduction and expanded ex vivo. Antigen-specific cytotoxicity was evaluated through in vitro coculture assays using selected patient-derived cell lines. Cytotoxic effects were quantified by 7-AAD via flow cytometry. Results Flow cytometry confirmed high surface expression of TROP-2 (83%), c-KIT (88%), and CD70 (99%) in T1889, Kasumi, and U266 cell lines, respectively. Lentiviral transduction produced Fab⁺ CAR-T populations of 48.2% (TROP-2), 24.7% (c-KIT), and 47.5% (CD70). All three CAR-T constructs showed antigen-specific cytotoxicity significantly greater than GFP⁺ CD3⁺ controls. Conclusions This study provides early in vitro evidence supporting CAR T-cell therapy targeting TROP-2, c- KIT, and CD70 for thymic carcinoma. Results confirm strong CAR expression and potent, selective killing of antigen-positive targets.
2022-10-17 | Upper thoracic empyema and concomitant superior vena cava syndrome treated with reconstructive surgery using a pedicled omental flap.
Superior vena cava (SVC) syndrome refers to a constellation of symptoms secondary to obstruction of blood flow through the SVC. In this condition, venous blood that usually drains into the SVC is diverted into the inferior vena cava (IVC) via collateral veins. Reconstructive surgery is challenging in such cases owing to the anomalous venous system. In this case report, we describe reconstructive surgery using a pedicled omental flap in a patient with upper thoracic empyema and concomitant SVC syndrome. A 68-year-old man underwent resection of malignant thymoma, the bilateral brachiocephalic veins, and a part of the right upper lobe, followed by polytetrafluoroethylene (PTFE) graft placement for venous system reconstruction, 2 years prior to presentation. He developed postoperative upper thoracic cavity empyema, which necessitated PTFE graft removal. Although the infection was controlled after 2 months, multiple right upper lobe pulmonary fistulas persisted, and the patient was referred to our department for further evaluation. Contrast-enhanced computed tomography revealed SVC syndrome characterized by SVC obstruction and consequent drainage of venous blood from the upper trunk into the IVC via collateral vessels. We debrided necrotic and infected tissues, and a pedicled omental flap was placed for upper lobe fistula coverage. The patient showed an uncomplicated postoperative course, and no recurrent empyema or pulmonary fistulas were observed 3 years postoperatively. Flaps associated with the SVC system show high venous pressures. The use of a pedicled omental flap was deemed feasible because this graft reaches the upper thorax even though it is associated with the IVC system.
2020-09-18 | Myasthenia Gravis Related to Thymic Carcinoma: A Case Study
Myasthenia gravis and thymoma are often presented in association with ∼10% of myasthenic cases having concomitant thymoma. Thymic carcinoma is one of the rarest/aggressive human epithelial tumors and has no correlation with myasthenia gravis hitherto. Here is provided a clinical case and review of literature on a very rare association of thymic carcinoma (with no sign of thymoma) and myasthenia gravis (antiacetylcholine receptor antibody positive). Two years after thymectomy, clinical evolution was satisfactory. This clinical case elicits hypothesis that thymic carcinoma may be related with myasthenia gravis, what may have good prognostic from oncologic and neurologic perspectives.
other
2024-09-26 | Characteristics of GTF2I L424H Mutated Thymoma and its Prognostic Impact: A Comprehensive Study
Thymic Epithelial Tumor (TET), a rare thoracic tumor, including thymoma and thymic carcinoma, has limited research on thymoma prognostic markers compared to thymic carcinoma. Using the cBiportal database, we analyzed gene expression, methylation, and mutation data in TETs. We explored the relationship between the GTF2I L424H mutation and thymoma pathology through differential gene expression, pathway enrichment analyses, and COX regression to develop a thymoma risk score. Compared with GTF2I wild-type, patients harboring GTF2I L424H mutation displayed distinctive gene expression and methylation profiles, resembling differences between pathology low-risk and high-risk patients. Importantly, patients with the GTF2I L424H mutation demonstrated a better prognosis than wild-type patients, but no such distinction was noted between low-risk and high-risk patients. Pathway analysis suggested that the mutation potentially regulates tumor development-related pathways, including the P53, Hippo, and TGFβ signaling pathways, ECM-receptor interaction, and tumor immune cell infiltration. Additionally, ten hub genes identified by cytoHubba, FGF20, FGF10, EGF, and TWIST1 were selected by stepwise multivariate Cox regression to construct a risk score model for thymoma. These findings highlight the potential role of the GTF2I L424H mutation as a prognostic factor, advocating for genetic profiling in personalized treatment strategies.
2024-05-01 | Long non-coding RNA LOXL1-AS1: a potential biomarker and therapeutic target in human malignant tumors.
Long non-coding RNAs (lncRNAs) are transcripts that contain more than 200 nucleotides. Despite their inability to code proteins, multiple studies have identified their important role in human cancer through different mechanisms. LncRNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1), a newly discovered lncRNA located on human chromosome 15q24.1, has recently been shown to be involved in the occurrence and progression of various malignancies, such as colorectal cancer, gastric cancer, hepatocellular carcinoma, prostate cancer, non-small cell lung cancer, ovarian cancer, cervical cancer, breast cancer, glioma, thymic carcinoma, pancreatic carcinoma. LOXL1-AS1 acts as competitive endogenous RNA (ceRNA) and via sponging various miRNAs, including miR-374b-5p, miR-21, miR-423-5p, miR-589-5p, miR-28-5p, miR-324-3p, miR-708-5p, miR-143-3p, miR-18b-5p, miR-761, miR-525-5p, miR-541-3p, miR-let-7a-5p, miR-3128, miR-3614-5p, miR-377-3p and miR-1224-5p to promote tumor cell proliferation, invasion, migration, apoptosis, cell cycle, and epithelial-mesenchymal transformation (EMT). In addition, LOXL1-AS1 is involved in the regulation of P13K/AKT and MAPK signaling pathways. This article reviews the current understanding of the biological function and clinical significance of LOXL1-AS1 in human cancers. These findings suggest that LOXL1-AS1 may be both a reliable biomarker and a potential therapeutic target for cancers.
2023-10-31 | 1214 IL-12 vectors engineered to encode a functional p35-p40 heterodimer or a single p35 subunit for cancer immunotherapy
Interleukin-12 (IL-12) is a 70-kDa heterodimeric cytokine composed of a 35 kDa(p35) and a 40 kDa subunit(p40). IL-12 has been proven to be a potent anticancer agent as it promotes the development of anti-tumor CD8+ T cells and NK cells. Although IL-12 has shown robust antitumor activity in preclinical studies and potent immune-stimulating potential in humans, there are no approved IL-12 therapeutic products due to its systemic toxicities. The IL-12 vectors described here are non-replicating MLV retrovectors which transduce rapidly dividing cells. Two types of IL-12 vectors were engineered. In the first type, both p35 and p40 are encoded for and linked by self-cleaving T2A peptide whereas in the second, only the p35 is encoded. The latter vector may be suitable for transducing tumor types that overexpress p40 such as squamous cell tumors.1 IL-12 tumor specificity can be achieved through local delivery of the vector, targeting via PiT2 receptors, the transduction and integration of rapidly dividing tumor cells, and/or pseudotyping the vector envelope to target tumor specific surface receptors. All IL-12 genes were synthesized at Genscript and the final plasmids were confirmed by whole plasmid sequencing at Primordium Labs. Human A375 melanoma cells were transduced by the first IL-12 vector and subjected to Western blotting to confirm the protein expression of the two subunits. Both human and murine IL-12 as well as human p35 vectors were produced and tested. An mIL-12 expressing mouse colorectal CT26 stable cell line was established. P40 subunit vector was also separately engineered and used to generate A375-P40 overexpressing cells. Functional IL-12(p70) was tested by mIL-12 or hIL-12 ELISAs and in vitro assays. The IL-12 vector encoding for the two subunits can successfully transduce mouse and human cancer cells which then express and secrete biologically functional IL-12. The other vector encoding for p35 only, when transducing a p40 expressing cell line, produces and secretes a fully functional p70(IL-12) as well. The data indicate the potential use of our IL-12 vectors as an efficient delivery system in IL-12 cancer gene therapy. Pre-clinical studies in a mouse tumor model of colorectal cancer demonstrate that IL-12 vector transduced tumors generate a significant immune response, inhibit tumor growth, and increase survival rate. Our current focus is the investigation of pseudotyped IL-12 vectors to target tumor specific surface receptors in in vivo tumor models. Karlin, et al. J Cancer Metastasis Treat, 2022;8:15, Review: Thymic carcinoma: review and update.
2022-04-22 | Long Non-Coding RNAs in the Cell Fate Determination of Neoplastic Thymic Epithelial Cells
Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine tumors that still require in-depth molecular characterization. Long non-coding RNAs (lncRNAs) are emerging as relevant gene expression modulators involved in the deregulation of several networks in almost all types of human cancer, including TETs. LncRNAs act at different control levels in the regulation of gene expression, from transcription to translation, and modulate several pathways relevant to cell fate determination under normal and pathological conditions. The activity of lncRNAs is strongly dependent on their expression, localization, and post-transcriptional modifications. Starting from our recently published studies, this review focuses on the involvement of lncRNAs in the acquisition of malignant traits by neoplastic thymic epithelial cells, and describes the possible use of these molecules as targets for the design of novel therapeutic approaches specific for TET. Furthermore, the involvement of lncRNAs in myasthenia gravis (MG)-related thymoma, which is still under investigation, is discussed.
2022-04-19 | Construction of immune-related LncRNAs classifier to predict prognosis and immunotherapy response in thymic epithelial tumors
The primary objective of this study was to construct an immune-related long noncoding RNAs (IRLs) classifier to precisely predict the prognosis and immunotherapy response of patients with thymic epithelial tumors (TET). Based on univariable Cox regression analysis and Lasso regression, six prognosis-related IRLs (AC004466.3, AC138207.2, AC148477.2, AL450270.1, HOXB-AS1 and SNHG8) were selected to build an IRL classifier. Importantly, results of qRT-PCR validated that higher expression levels of AC138207.2, AC148477.2, AL450270.1 and SNHG8 as well as lower expression levels of AC004466.3, and HOXB-AS1 in TETs samples compared with normal controls. The IRL classifier could effectively classify patients into the low-risk and high-risk groups based on the different survival parameters. In terms of predictive ability and clinical utility, the IRL classifier was superior to Masaoka staging system. Additionally, IRL classifier is significantly associated with immune cells infiltration (dendritic cells, activated CD4 memory T cells and tumor-infiltrating lymphocyte (TIL), T cell subsets in particular), immune microenvironment (immune score and immune checkpoint inhibitors) and immunogenicity (TMB) in TETs, which hints that IRL classifier is tightly correlated with immune characteristics and might guide more effective immunotherapy strategies for TETs patients. Encouragingly, according to TIDE algorithm, there were more immunotherapy responders in the low-risk IRL subgroup and the IRL score was robustly negatively linked to the immunotherapeutic response. To sum up, the IRL classifier was established, which can be used to predict the prognosis, immune infiltration status, immunotherapy response in TETs patients, and may facilitate personalized counseling for immunotherapy.
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Drug Discovery Landscape
1 orphan drug designation for Thymic carcinoma.
1 orphan drug designation for Thymic carcinoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
(1R,2R)-1,2-cyclohexane-diaminepyrophosphato-platinum(II) | small molecules | FDA | 2018-10-25 | — | Promontory Therapeutics, Inc. |
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