RARE DISEASE
Primary peritoneal carcinoma
Primary peritoneal carcinoma
Primary peritoneal carcinoma
Synonyms: EOPPC, Extra-ovarian primary peritoneal carcinoma, PPC, Primary peritoneal serous carcinoma, Serous surface papillary carcinoma
Synonyms: EOPPC, Extra-ovarian primary peritoneal carcinoma, PPC, Primary peritoneal serous carcinoma, Serous surface papillary carcinoma
Synonyms: EOPPC, Extra-ovarian primary peritoneal carcinoma, PPC, Primary peritoneal serous carcinoma, Serous surface papillary carcinoma
Drug discovery
7
drugs
With orphan designations
Overview
Primary peritoneal carcinoma (PPC) is a rare, aggressive malignancy arising from the peritoneal lining, clinically and histologically resembling ovarian serous carcinoma [1][3][6]. It predominantly affects postmenopausal women (median age 60–72), with BRCA1/2 mutations increasing lifetime risk by ~5% even after oophorectomy [1][3][15]. Diagnosis requires exclusion of ovarian primaries, and most present with advanced-stage disease (Stage III/IV), ascites, and elevated CA-125 [4][6][11]. Treatment mirrors ovarian cancer, combining cytoreductive surgery and platinum-taxane chemotherapy, but prognosis remains poor (median survival 12–17 months) [1][5][13].
Burden
Prognosis: Median survival 12–17 months, 5-year survival ~26% [1][4][11].
Morbidity: Advanced-stage diagnoses (70–80%) cause ascites, bowel obstruction, and cachexia, requiring palliative interventions (paracentesis, stenting) [8][15][17].
Recurrence: >75% relapse within 2 years, necessitating secondary-line therapies (gemcitabine, pegylated liposomal doxorubicin) [8][18].
Therapies
First-line: Cytoreductive surgery (optimal debulking) with hyperthermic intraperitoneal chemotherapy (HIPEC) [3][9][17], followed by platinum-paclitaxel systemic chemotherapy [8][13].
Targeted therapies: PARP inhibitors (olaparib, niraparib) for BRCA-mutated cases and bevacizumab for advanced/metastatic disease [8][13][17].
Advanced disease: Neoadjuvant chemotherapy for unresectable tumors, with interval debulking if responsive [5][8][13].
Categories: rare abdominal surgical diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
652 drug discovery papers related to Primary peritoneal carcinoma, with 4 first-in-class and 1 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
652 drug discovery papers related to Primary peritoneal carcinoma, with 4 first-in-class and 1 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-09 | Single-cell transcriptomics of heterogeneous patient-derived organoids reveals novel therapeutic targets in high-grade serous ovarian cancer
Abstract High-grade serous ovarian carcinoma (HGSOC) is characterized by widespread peritoneal dissemination and poor long-term survival, largely driven by metastatic relapse following initial response to chemotherapy. Defining the molecular programs that enable tumor progression from the primary ovarian site to metastatic niches remains a key challenge. Here, we leverage patient-derived organoids (PDOs) coupled with single-cell RNA sequencing (scRNA-seq) to interrogate tumor evolution and identify regulators of metastatic competence in HGSOC. We profiled PDOs and matched formalin-fixed paraffin-embedded (FFPE) tumor samples from ovarian and omental disease sites across seven patients. Single-cell transcriptomic analysis revealed conserved and patient-specific cellular states and enabled reconstruction of inferred trajectories of tumor progression. Comparative trajectory analysis identified gene expression programs associated with metastatic transition from ovarian to omental tumors. Among these, the heparan sulfate proteoglycan AGRIN emerged as a consistently upregulated gene along the metastatic axis. Cell-cell communication analyses suggested that AGRIN -mediated signaling involves both epithelial tumor cells and stromal components, implicating the extracellular matrix in shaping metastatic behavior through mechanotransduction and integrin-associated pathways. Functional validation using genetic depletion of AGRIN in ovarian cancer cell lines demonstrated reduced migratory and invasive capacity, supporting a causal role for AGRIN in promoting metastatic phenotypes. Together, these findings identify AGRIN as a regulator of metastatic competence in HGSOC and highlight extracellular matrix–associated signaling as a key driver of disease progression. More broadly, this study demonstrates that PDO-based single-cell transcriptomic approaches can uncover actionable regulators of metastasis and provide a scalable framework for therapeutic target discovery across cancer types. Significance Patient-derived organoids analyzed by single-cell transcriptomics reveal dynamic tumor evolution and uncover AGRIN as a regulator of metastatic competence in HGSOC, demonstrating the utility of living tumor models for therapeutic target discovery.
2026-05-28 | Study design of OMAHA-015: A phase 2 basket study of steroidogenesis inhibitor opevesostat in participants with selected solid tumors.
TPS3183 Background: Opevesostat (MK-5684; ODM-208), an oral steroidogenesis inhibitor, selectively inhibits CYP11A1, blocking synthesis of all steroid hormones and their precursors, and may suppress steroid-driven tumor growth. The randomized, open-label, phase 2 OMAHA-015 trial (NCT06979596) is designed to evaluate the efficacy and safety of opevesostat compared with standard of care in breast, ovarian, and endometrial cancers. Methods: Cohort A will enroll participants (pts) with locally advanced unresectable or metastatic hormone receptor–positive (estrogen receptor and/or progesterone receptor ≥1% expression)/HER2-negative breast cancer (IHC 0, 1+ or 2+/ISH-) and disease progression on or after ≥1 prior endocrine-based therapy in the metastatic setting. Exclusion criteria include any line of cytotoxic chemotherapy (chemo) or PARP inhibitor in the inoperable or noncurative advanced/metastatic setting and prior treatment with both fulvestrant and exemestane in the metastatic setting. Cohort B will enroll pts with platinum-sensitive, histologically confirmed high-grade epithelial ovarian (including high-grade serous or predominantly serous, high-grade endometrioid, clear cell, or malignant mixed Müllerian tumors [carcinosarcoma]), fallopian tube, or primary peritoneal carcinomas. Pts must have received 4-8 cycles of platinum-based doublet chemo in a third-line setting for ovarian cancer with ≤9 weeks between the last dose of third-line chemo and randomization. Cohort C will enroll pts with histologically confirmed primary advanced or recurrent low-grade endometrioid carcinoma (FIGO grade 1/2, or well/moderately differentiated), with known pMMR status, and wild type p53 expression. Pts must either be treatment naive or have received 1 prior line of platinum-based therapy in the advanced/metastatic or adjuvant/neoadjuvant setting. In cohort A, ~80 pts will be randomized 1:1 to arm 1: opevesostat 5 mg PO twice daily (BID) + daily corticosteroids or arm 2: physician’s decision of fulvestrant 500 mg IM (D1 and D15 of cycle 1 and D1 of each cycle thereafter) or exemestane 25 mg PO daily. Randomization will be stratified by 1 line versus ≥2 lines of prior endocrine therapy. In cohort B, ~90 pts will be randomized 1:1 to arm 3: opevesostat 5 mg PO BID + daily corticosteroids; or arm 4: observation. In cohort C, ~80 pts will be randomized 1:1 to arm 5: opevesostat 5 mg PO BID + daily corticosteroids; or arm 6: physician’s choice of megestrol acetate 80 mg PO BID, alternating megestrol + tamoxifen 20 mg PO BID, or letrozole 2.5 mg PO daily. The primary end point is progression-free survival per RECIST v1.1 assessed by blinded independent central review (BICR). Secondary end points include overall survival, clinical benefit rate (cohort A only), objective response rate, and duration of response per RECIST v1.1 assessed by BICR, and safety. The study is currently enrolling. Clinical trial information: NCT06979596 .
2026-05-27 | Dose-dense weekly versus standard three-weekly paclitaxel in combination with carboplatin for resectable stage II-IV epithelial ovarian carcinoma: A retrospective cohort study.
5568 Background: Dose-dense weekly paclitaxel combined with carboplatin has demonstrated variable efficacy in first-line treatment of resectable epithelial ovarian cancer across different populations. While Japanese and selected real-world studies suggest improved outcomes, large Western trials have failed to confirm a survival advantage. Data from South Asian populations remains limited. This study compared progression-free survival (PFS), overall survival (OS), and toxicity profiles of dose-dense versus standard three-weekly paclitaxel plus carboplatin in a real-world, resource-constrained setting. Methods: This single-center retrospective cohort study included women aged ≥20 years with resectable, FIGO stage II–IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treated between January 2015 and December 2018. Patients received first-line carboplatin at an AUC of 5 (Area Under Curve 5) with either dose-dense weekly paclitaxel (80 mg/m² on days 1, 8, and 15) or standard three-weekly paclitaxel (175 mg/m²). Kaplan–Meier methods were used to estimate PFS and OS, and comparisons were performed using the log-rank test. Cox proportional hazards models were applied for univariate and multivariate analyses. Results: Seventy-two patients were included, 36 in each arm. The majority presented with stage III disease (63.9% in the dose-dense arm vs. 52.8% in the standard arm). High-grade serous carcinoma was the predominant histology in both groups (83% vs. 75%). The distribution of primary versus interval debulking surgery and rates of residual disease were similar between the two arms. The dose-dense regimen was associated with significantly improved PFS compared with the standard schedule (mean PFS 25 vs. 18 months; 95% CI: 23.1-28.4; log-rank p = 0.01); median PFS was 32 months in the dose-dense arm, whereas it could not be estimated in the standard arm. OS favoured the dose-dense group (mean OS of 56 vs. 50 months), although this difference was not statistically significant (p = 0.27). In the multivariate analysis of the dose-dense cohort, elevated baseline Ca-125 (HR = 6.80; 95% CI: 1.38–34.20; p = 0.01) and cytoreduction type (HR = 13.30; 95% CI: 1.90–90.20; p = 0.008) were independent predictors of PFS but not for OS. Rates of grade ≥3 treatment-related adverse events were comparable between arms, while sensory neuropathy occurred more frequently with dose-dense therapy (39% vs. 28%). Conclusions: This real-world analysis supports the use of dose-dense weekly paclitaxel combined with carboplatin for improved PFS, findings consistent with some regional studies. While OS data showed a non-significant trend favouring the dose-dense regimen with some risk of neuropathy, they highlight the need for larger prospective regional studies to better define patient populations most likely to benefit.
2026-06-09 | Single-cell transcriptomics of heterogeneous patient-derived organoids reveals novel therapeutic targets in high-grade serous ovarian cancer
Abstract High-grade serous ovarian carcinoma (HGSOC) is characterized by widespread peritoneal dissemination and poor long-term survival, largely driven by metastatic relapse following initial response to chemotherapy. Defining the molecular programs that enable tumor progression from the primary ovarian site to metastatic niches remains a key challenge. Here, we leverage patient-derived organoids (PDOs) coupled with single-cell RNA sequencing (scRNA-seq) to interrogate tumor evolution and identify regulators of metastatic competence in HGSOC. We profiled PDOs and matched formalin-fixed paraffin-embedded (FFPE) tumor samples from ovarian and omental disease sites across seven patients. Single-cell transcriptomic analysis revealed conserved and patient-specific cellular states and enabled reconstruction of inferred trajectories of tumor progression. Comparative trajectory analysis identified gene expression programs associated with metastatic transition from ovarian to omental tumors. Among these, the heparan sulfate proteoglycan AGRIN emerged as a consistently upregulated gene along the metastatic axis. Cell-cell communication analyses suggested that AGRIN -mediated signaling involves both epithelial tumor cells and stromal components, implicating the extracellular matrix in shaping metastatic behavior through mechanotransduction and integrin-associated pathways. Functional validation using genetic depletion of AGRIN in ovarian cancer cell lines demonstrated reduced migratory and invasive capacity, supporting a causal role for AGRIN in promoting metastatic phenotypes. Together, these findings identify AGRIN as a regulator of metastatic competence in HGSOC and highlight extracellular matrix–associated signaling as a key driver of disease progression. More broadly, this study demonstrates that PDO-based single-cell transcriptomic approaches can uncover actionable regulators of metastasis and provide a scalable framework for therapeutic target discovery across cancer types. Significance Patient-derived organoids analyzed by single-cell transcriptomics reveal dynamic tumor evolution and uncover AGRIN as a regulator of metastatic competence in HGSOC, demonstrating the utility of living tumor models for therapeutic target discovery.
2026-05-28 | Study design of OMAHA-015: A phase 2 basket study of steroidogenesis inhibitor opevesostat in participants with selected solid tumors.
TPS3183 Background: Opevesostat (MK-5684; ODM-208), an oral steroidogenesis inhibitor, selectively inhibits CYP11A1, blocking synthesis of all steroid hormones and their precursors, and may suppress steroid-driven tumor growth. The randomized, open-label, phase 2 OMAHA-015 trial (NCT06979596) is designed to evaluate the efficacy and safety of opevesostat compared with standard of care in breast, ovarian, and endometrial cancers. Methods: Cohort A will enroll participants (pts) with locally advanced unresectable or metastatic hormone receptor–positive (estrogen receptor and/or progesterone receptor ≥1% expression)/HER2-negative breast cancer (IHC 0, 1+ or 2+/ISH-) and disease progression on or after ≥1 prior endocrine-based therapy in the metastatic setting. Exclusion criteria include any line of cytotoxic chemotherapy (chemo) or PARP inhibitor in the inoperable or noncurative advanced/metastatic setting and prior treatment with both fulvestrant and exemestane in the metastatic setting. Cohort B will enroll pts with platinum-sensitive, histologically confirmed high-grade epithelial ovarian (including high-grade serous or predominantly serous, high-grade endometrioid, clear cell, or malignant mixed Müllerian tumors [carcinosarcoma]), fallopian tube, or primary peritoneal carcinomas. Pts must have received 4-8 cycles of platinum-based doublet chemo in a third-line setting for ovarian cancer with ≤9 weeks between the last dose of third-line chemo and randomization. Cohort C will enroll pts with histologically confirmed primary advanced or recurrent low-grade endometrioid carcinoma (FIGO grade 1/2, or well/moderately differentiated), with known pMMR status, and wild type p53 expression. Pts must either be treatment naive or have received 1 prior line of platinum-based therapy in the advanced/metastatic or adjuvant/neoadjuvant setting. In cohort A, ~80 pts will be randomized 1:1 to arm 1: opevesostat 5 mg PO twice daily (BID) + daily corticosteroids or arm 2: physician’s decision of fulvestrant 500 mg IM (D1 and D15 of cycle 1 and D1 of each cycle thereafter) or exemestane 25 mg PO daily. Randomization will be stratified by 1 line versus ≥2 lines of prior endocrine therapy. In cohort B, ~90 pts will be randomized 1:1 to arm 3: opevesostat 5 mg PO BID + daily corticosteroids; or arm 4: observation. In cohort C, ~80 pts will be randomized 1:1 to arm 5: opevesostat 5 mg PO BID + daily corticosteroids; or arm 6: physician’s choice of megestrol acetate 80 mg PO BID, alternating megestrol + tamoxifen 20 mg PO BID, or letrozole 2.5 mg PO daily. The primary end point is progression-free survival per RECIST v1.1 assessed by blinded independent central review (BICR). Secondary end points include overall survival, clinical benefit rate (cohort A only), objective response rate, and duration of response per RECIST v1.1 assessed by BICR, and safety. The study is currently enrolling. Clinical trial information: NCT06979596 .
2026-05-27 | Dose-dense weekly versus standard three-weekly paclitaxel in combination with carboplatin for resectable stage II-IV epithelial ovarian carcinoma: A retrospective cohort study.
5568 Background: Dose-dense weekly paclitaxel combined with carboplatin has demonstrated variable efficacy in first-line treatment of resectable epithelial ovarian cancer across different populations. While Japanese and selected real-world studies suggest improved outcomes, large Western trials have failed to confirm a survival advantage. Data from South Asian populations remains limited. This study compared progression-free survival (PFS), overall survival (OS), and toxicity profiles of dose-dense versus standard three-weekly paclitaxel plus carboplatin in a real-world, resource-constrained setting. Methods: This single-center retrospective cohort study included women aged ≥20 years with resectable, FIGO stage II–IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treated between January 2015 and December 2018. Patients received first-line carboplatin at an AUC of 5 (Area Under Curve 5) with either dose-dense weekly paclitaxel (80 mg/m² on days 1, 8, and 15) or standard three-weekly paclitaxel (175 mg/m²). Kaplan–Meier methods were used to estimate PFS and OS, and comparisons were performed using the log-rank test. Cox proportional hazards models were applied for univariate and multivariate analyses. Results: Seventy-two patients were included, 36 in each arm. The majority presented with stage III disease (63.9% in the dose-dense arm vs. 52.8% in the standard arm). High-grade serous carcinoma was the predominant histology in both groups (83% vs. 75%). The distribution of primary versus interval debulking surgery and rates of residual disease were similar between the two arms. The dose-dense regimen was associated with significantly improved PFS compared with the standard schedule (mean PFS 25 vs. 18 months; 95% CI: 23.1-28.4; log-rank p = 0.01); median PFS was 32 months in the dose-dense arm, whereas it could not be estimated in the standard arm. OS favoured the dose-dense group (mean OS of 56 vs. 50 months), although this difference was not statistically significant (p = 0.27). In the multivariate analysis of the dose-dense cohort, elevated baseline Ca-125 (HR = 6.80; 95% CI: 1.38–34.20; p = 0.01) and cytoreduction type (HR = 13.30; 95% CI: 1.90–90.20; p = 0.008) were independent predictors of PFS but not for OS. Rates of grade ≥3 treatment-related adverse events were comparable between arms, while sensory neuropathy occurred more frequently with dose-dense therapy (39% vs. 28%). Conclusions: This real-world analysis supports the use of dose-dense weekly paclitaxel combined with carboplatin for improved PFS, findings consistent with some regional studies. While OS data showed a non-significant trend favouring the dose-dense regimen with some risk of neuropathy, they highlight the need for larger prospective regional studies to better define patient populations most likely to benefit.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
7 orphan drug designations for Primary peritoneal carcinoma, including 2 approved therapies.
7 orphan drug designations for Primary peritoneal carcinoma, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Gleolan | small molecules | FDA | 2024-02-15 | — | NX Development Corp. |
olaparib [Lynparza] | small molecules | FDA | 2018-05-15 | 2017-08-17 | AstraZeneca Pharmaceuticals LP |
antibody drug conjugate targeting dipeptidase 3 (DPEP3) | antibodies | FDA | 2018-01-08 | — | AbbVie Stemcentrx, LLC |
pelareorep | gene therapies | FDA | 2015-02-24 | — | Oncolytics Biotech, Inc. |
bevacizumab [Avastin] | antibodies | FDA | 2010-11-02 | 2014-11-14 | Genentech, Inc. |
patupilone | small molecules | FDA | 2010-02-02 | — | Novartis Pharmaceuticals Corporation |
Patupilone | small molecules | EMA | 2009-11-05 | — | Novartis Europharm Limited |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.