Zejula (niraparib) / Medison, GSK, ZAI Lab, J&J, Takeda - LARVOL DELTA

Phase 3 AMPLITUDE trial: Niraparib (NIRA) and abiraterone acetate plus prednisone (AAP) for metastatic castration-sensitive prostate cancer (mCSPC) patients (pts) with alterations in homologous recombination repair (HRR) genes. (BASCO-MN 2025) - No abstract available

Clinical • Late-breaking abstract • Metastases • P3 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD

Combinatorial organoid mutagenesis screen reveals gene constellations driving malignant transformation, pathology and chemosensitivity in high-grade serous ovarian carcinoma. (PubMed, bioRxiv) - "Map2k4-mutant organoids were more sensitive to paclitaxel and niraparib, while Nf1-mutant combinations responded better to trametinib. Collectively, our results demonstrate that TE-derived organoids coupled with combinatorial CRISPR mutagenesis provide a powerful system to unravel the genetic and phenotypic complexity of HGSC. In particular, we found that Map2k4 functions as a tumor suppressor that shapes distinct tumor histology and chemosensitivity, suggesting it as a potential therapeutic target in select HGSC cases."

Journal • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • Transplantation • CDKN2A • MAP2K4 • NF1 • PVT1 • TP53

LIBINI-1: Design and Validation of Plasma Proteins and Cytokine Panels to Identify Markers Associated With Response to Niraparib as Maintenance Treatment After First-line Platinum-based Regimen in Patients With Advanced Ovarian Cancer (clinicaltrials.gov) - P=N/A | N=120 | Not yet recruiting | Sponsor: Clinica Universidad de Navarra, Universidad de Navarra

New trial • Oncology • Ovarian Cancer • Solid Tumor

QPT-ORE-004: A Clinical Study Evaluating a Combination of Oregovomab and Niraparib in Adult Women With Platinum Sensitive Recurrent Ovarian Cancer. (clinicaltrials.gov) - P2 | N=10 | Active, not recruiting | Sponsor: CanariaBio Inc. | Trial completion date: Dec 2024 ➔ Jul 2025 | Trial primary completion date: Mar 2024 ➔ Mar 2025

Platinum sensitive • Trial completion date • Trial primary completion date • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • MUC16

Precision medicine in colorectal cancer: Personalizing treatment for improved outcomes? (ESMO-GI 2025) - "Other MTT: KRAS G12C inhibitor + Cetuximab (N=18), pan-RAS inhibitor for KRAS G12Cm (N=1), Encorafenib + Cetuximab (N=14) and Dabrafenib + Trametinib (N=1) for BRAF V600Em, Trastuzumab Deruxtecan (N=3) and Tucatinib + Trastuzumab for HER2m/a (N=1), Trametinib for MEKm (N=2), anti LGR5-EGFR bispecific antibody for EGFRm (N=1), Niraparib + Dostarlimab for ARID1Am (N=1), Alectinib for ALKf(N=1) and Inavolisib for PIK3CAm (N=1). Despite no obvious OS benefit of MTT due to small pts number and late MTT lines, this study highlights the different potential targetable MA in 28.9% of pts excluding non G12C RASm. Impact of novel RAS inhibitors and other MTT might change mCRC precision medicine."

IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • ALK • ARID1A • BRAF • KRAS

Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302) (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | N=60 ➔ 130

Enrollment change • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

ROCSAN: Recurrent Ovarian CarcinoSarcoma Anti-pd-1 Niraparib (clinicaltrials.gov) - P2/3 | N=138 | Recruiting | Sponsor: ARCAGY/ GINECO GROUP | Active, not recruiting ➔ Recruiting | Trial completion date: Jun 2025 ➔ Jun 2027 | Trial primary completion date: Dec 2024 ➔ Jun 2027

Enrollment open • Trial completion date • Trial primary completion date • Carcinosarcoma • Endometrial Cancer • Endometrial Carcinosarcoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor

OVATION-3: Phase 3 Trial Evaluating the Safety & Efficacy of IMNN-001 Administered in Combination w/ Standard NACT & Adjuvant Chemotherapy in Newly Diagnosed Patients w/ Advanced EOC, Fallopian Tube or Primary Peritoneal Cancer (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Imunon | Not yet recruiting ➔ Recruiting

Enrollment open • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

MORPHEUS mUC: Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC) (clinicaltrials.gov) - P1/2 | N=272 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: May 2026 ➔ Oct 2025 | Trial primary completion date: Oct 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

Exploring the radiochemistry of PARP inhibitors: a new era in therapy and imaging. (PubMed, EJNMMI Radiopharm Chem) - "Finally, emerging evidence suggest the possibility to involve PARP-related radiopharmaceuticals in theranostics approaches. Despite challenges such as the complexity of radiolabelling, regulatory hurdles, and the need for more robust clinical validation, the continued exploration of the radiochemistry of PARP inhibitors promises to revolutionize both the diagnosis and treatment of cancer, offering hope for more effective and personalized cancer care."

Journal • Review • Breast Cancer • Oncology • Solid Tumor • BRCA

A phase 2 trial of niraparib plus bevacizumab maintenance therapy following first-line platinum-based chemotherapy with bevacizumab in advanced ovarian cancer: final analysis and overall survival results from OVARIO. (PubMed, Gynecol Oncol) - P2 | "In OVARIO, median OS was 61.1 months in the overall population. Safety was consistent with known safety profiles of niraparib and bevacizumab as monotherapies."

Journal • P2 data • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • HRD

Update Gynecologic Malignancies 2025 - Expert Opinion on Systemic Therapy for Early and Advanced Gynecological Cancers. (PubMed, Geburtshilfe Frauenheilkd) - "The treatment of advanced endometrial cancer has changed significantly with the introduction of CPI such as dostarlimab (RUBY trial), durvalumab (DUO-E trial) and pembrolizumab (Keynote-868 trial). For ovarian cancer PARPi have shown substantial PFS benefits in key approval trials, including PRIMA for niraparib, PAOLA for olaparib, and ATHENA-MONO for rucaparib...Furthermore, mirvetuximab soravtansine is the first antibody-drug conjugate (ADC) approved in Germany for platinum-resistant ovarian cancer for patients with folate receptor alpha expression...With the increased use of ADCs, this is not the end of these developments. Therapy algorithms from a certified German oncology center are developed and presented in this article."

IO biomarker • Journal • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

Establishment of chemoresistant patient-derived tumor organoids (PDTO) to identify relevant biomarkers for second-line treatments in ovarian cancer (EACR 2025) - "Introduction: Ovarian cancer has a poor clinical prognosis due to innate or acquired chemoresistance following carboplatin/paclitaxel treatment...After each cycle, PDTOs were harvested to realize transcriptomic and proteomic analyses, to perform immunochemistry assay and to assess HRD profile.Result and Six cycles of carboplatin were sufficient to induce resistance in PDTOs to carboplatin and 2 PARP inhibitors (Olaparib and Niraparib), assessed by the increase of IC50 between the 1st and the 6th cycles... For the first time, our study highlights the possibility to establish an acquired resistance to carboplatin and PARP inhibitors in ovarian PDTO model. Future characterization of molecular pathways activation and biomarkers expression kinetics will represent an important scientific breakthrough and will offer new hope for second-line treatment of ovarian cancer."

Biomarker • Clinical • Oncology • Ovarian Cancer • Solid Tumor • BCL2L1 • HRD

miRNAs as biomarkers of PARP inhibitors resistance in ovarian Patient-Derived Tumor Organoids (EACR 2025) - "Five PDTO lines, sensitive to PARPi, will be treated for one week with a PARPi (niraparib or olaparib), at a dose corresponding to their IC50, for 6 cycles. This kinetic approach will make it possible to identify miRNAs whose expression evolves during the acquisition of resistance to PARPi, thus offering new avenues for identifying biomarkers for therapeutic monitoring."

Biomarker • Clinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Unravelling PARP inhibitor resistance mechanisms in ovarian cancer (EACR 2025) - "XRCC2, POLE2 and ERCC1 genes emerge as potential BKs of intrinsic resistance and that cell cycle overactivation could be an acquired resistance mechanism to PARPi in HGSOC."

Gynecologic Cancers • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CDK4 • CDKN1A • CDKN1B • CDKN2C • ERCC1 • RAD51 • XRCC2

Genomic Analysis of PARP Inhibitor Response in High-Grade Serous Ovarian Cancer: Insights from Whole Genome Sequencing (EACR 2025) - "Participants underwent surgery followed by adjuvant or neoadjuvant chemotherapy and maintenance therapy with olaparib or niraparib. This study suggests that WGS-based HRDetect can complement existing HRD assessment methods in HGSOC, offering a more comprehensive approach to identifying patients for targeted therapies."

Genomic analysis • Omic analysis • Whole genome sequencing • Fallopian Tube Cancer • High Grade Serous Ovarian Cancer • Microsatellite Instability • Oncology • Ovarian Cancer • Solid Tumor • BRCA • MSI

Malignant Ascites Derived Organoids from Ovarian Cancer Patients for Understanding Platinum Resistance and Approaching Targeted Therapy (EACR 2025) - "Three PDO models were tested for Carboplatin, Olaparib, and Niraparib response and were able to successfully mimic the platinum-treatment response. In this study, we demonstrated that PDOs derived from malignant ascites of HGSOC patients can recapitulate the histologic and molecular features of the patients' tumours, and can predict treatment response. These viable and relevant preclinical models are valuable tools to deep on the understanding of therapy resistance and to advance in precision medicine approaches for resistant HGSOC patients."

Clinical • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CDH1 • PAX8 • VIM

Facile and Practical Synthesis of Substituted Piperidine-2,6-Diones Under Transition-Metal Free Condition. (PubMed, ChemistryOpen) - "Furthermore, the application potential was further demonstrated by reaction scale-up (5 kilo-gram scale) and bio-active molecule synthesis (Aminoglutethimide and Niraparib). Additional control experiments revealed that the radical process could be excluded from this reaction and a michael addition/intramolecular imidation cascade sequence was proposed based on the control experiments. All these results demonstrated its significant application potential both in academic and industrial production."

Journal

Re: Gerhardt Attard, Neeraj Agarwal, Julie Graff, et al. Niraparib plus Abiraterone Acetate and Prednisone for HRR-mutated Metastatic Castration-sensitive Prostate Cancer: Results from the AMPLITUDE Phase 3 Trial. J Clin Oncol 2025;43(17 Suppl):LBA5006. (PubMed, Eur Urol Oncol) - No abstract available

Journal • P3 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Impact of Olaparib, Niraparib, Rucaparib therapies on Newly Diagnosed and Relapsed Ovarian Cancer -Systematic Review and Meta-Analysis. (PubMed, Asian Pac J Cancer Prev) - "PARPi are an effective therapy in both newly discovered and relapsed. Although there is a modest rise in the frequency of severe adverse reactions, they are usually handled well."

Journal • Retrospective data • Review • Hematological Disorders • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia

Synergistic strategies: ADC-PARP inhibitor combinations in triple-negative breast cancer therapy. (PubMed, Pathol Res Pract) - "ADCs like sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) target cytotoxic payloads with specificity, whereas PARPis like olaparib, rucaparib, niraparib, and talazoparib cause synthetic lethality in homologous recombination repair (HRR)-deficient tumors. Future directions include biomarker-driven patient selection, combination with immune checkpoint inhibitors, and advancement in next-generation ADCs. The synergistic potential of ADC-PARPi combinations provides a new avenue for overcoming TNBC resistance, enhancing treatment outcomes, and widening therapeutic strategies for this challenging disease."

IO biomarker • Journal • Review • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • HRD

Predictive factors of hematological toxicity in patients treated with PARPi in ovarian cancer (ESMO-GC 2025) - "Patients included received NIRAPARIB, OLAPARIB +/- BEVACIZUMAB according to molecular profile and the clinical risk. Clinical criteria and intensity of cytotoxic therapy delivered prior to PARPi initiation trend to be important such as baseline kidney function, apparition of hematotoxicity during chemotherapy and total dose of carboplatin and should alert us and lead to discuss the intensity of treatments for patients that will be potentially cured. Legal entity responsible for the study The authors."

Biomarker • Clinical • Oncology • Ovarian Cancer • Solid Tumor

Targeting PRDX1 to overcome PARPi resistance in ovarian cancer via mitochondrial dysfunction and suppressing mitophagy (ESMO-GC 2025) - "Conclusions Our findings provide novel insight into the multifaceted function of PRDX1 in regulating mitochondrial function of redox regulating, mitophagy, and OC Niraparib resistance. Disruption of PRDX1 may be a promising therapeutic strategy to overcome Niraparib resistance via leading to mitochondrial dysfunction and suppressing mitophagy."

Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • PRDX1

Impact of BRCA mutation location on PARPi response in advanced high-grade serous ovarian cancer (HGSOC): Real-world data from two tertiary university hospitals in Spain (ESMO-GC 2025) - "30 pts received first-line PARPi (26 olaparib and 4 niraparib). Median follow-up was 39 m (4-123). Conclusions In our study, BRCA1 RING or BRCT mutations showed poor PARPi response and survival, consistent with previous reports."

Clinical • Metastases • Real-world • Real-world evidence • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • PALB2 • RAD51

PRIMA vs real-world data: Patient characteristics and cancer outcomes (ESMO-GC 2025) - "Background First-line niraparib maintenance was approved in Scotland following the PRIMA trial but approval was broader than trial eligibility...As expected, PRIMA ineligible ZRD had best real-world outcomes. PFS2 in PRIMA eligible BRCAwt group was similar to PRIMA trial HRp group."

Clinical • Real-world • Real-world evidence • Gynecologic Cancers • Oncology • HRD