Rubraca (rucaparib) / Clovis, Pharma& Schweiz, Hikma, GHN Pharma - LARVOL DELTA

Detecting homologous recombination deficiency for breast cancer through integrative analysis of genomic data. (PubMed, Mol Oncol) - "Furthermore, our analysis of cell lines highlighted a sensitivity to PARP inhibitors, particularly rucaparib, among predicted HRD-positive lines. Exploring somatic mutations outside BRCA1/2, we confirmed variants in several genes associated with HRD. Our method for HRD classification can adapt to different data types or resolutions and can be used in various scenarios to help refine patient selection for HRD-targeting therapies that might lead to better clinical outcomes."

Journal • Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • ER • HRD

Novel APE1 endonuclease inhibitors as precision oncology therapeutics in high grade serous ovarian cancers discovered and developed from crystallography-based fragment library screening (AACR 2025) - "PARP1 inhibitor (Niraparib, Olaparib, Rucaparib) maintenance therapy improves progression-free survival in BRCA germline deficient ovarian cancer or platinum sensitive ovarian cancers. Olaparib and Talazoparib are approved for use in BRCA germ-line deficient breast cancers...Several compounds screened in MTS cell proliferation assay showed preferential cytotoxicity in PEO1 cells compared to PEO4 cells. Further cell based (clonogenics, 3D spheroids) and functional assays (DNA double strand break accumulation, cell cycle progression and apoptosis) are ongoing."

Breast Cancer • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Genito-urinary Cancer • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Cancer • Peritoneal Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2 • HRD

Real-world outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) receiving guideline-recommended therapies after treatment with 177Lu-PSMA-617: A real-world prostate cancer disease observation (PRECISION) data platform analysis. (ASCO-GU 2025) - "Guideline-recommended therapies included abiraterone, enzalutamide, darolutamide, apalutamide, cabazitaxel, docetaxel, pembrolizumab, sipuleucel-T, niraparib, olaparib, talazoparib, rucaparib, and radium-223. In this real-world analysis, the majority of patients who received guideline-recommended therapies after 177Lu-PSMA-617 achieved at least a PSA50 response, suggesting that 177Lu-PSMA-617 treatment does not preclude response to other subsequent therapies."

Clinical • Metastases • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Healthcare Resource Utilization (HCRU) and Costs of Poly(ADP-ribose) Polymerase Inhibitors (PARPi) as First-Line Maintenance (1LM) Treatment for Ovarian Cancer (OC) (ISPOR 2025) - "Key study inclusion criteria were ≥1 inpatient or ≥2 outpatient medical claims with an ICD-10-CM diagnosis code for ovarian, fallopian tube, or peritoneum cancer (collectively referred to as OC; January 1, 2017-June 30, 2022); initiated first-line (1L) platinum-based chemotherapy after the OC diagnosis; initiated 1LM PARPi monotherapy (niraparib, olaparib, or rucaparib) within 180 days of 1L platinum-based chemotherapy discontinuation (index date); and continuous enrollment during the 12 months preceding the OC diagnosis (baseline) through 30 days post-index. Results of this real-world analysis highlight that 1LM PARPi monotherapy use was associated with relatively low HCRU and mean medical costs in the 6 months after PARPi initiation."

Clinical • HEOR • Oncology • Ovarian Cancer • Solid Tumor

Establishment and characterization of a panel of ovarian XPDX models from patients with clinical resistance to anti-folate receptor therapies (AACR 2025) - "These models were characterized by DNA and RNA sequencing, folate receptor expression, and in vivo sensitivity to various therapies including MIRV. Four post-FRα ovarian XPDX models were established and characterized: ST409 was from a 59-year-old Hispanic female pretreated with chemotherapy and eleven months of farletuzumab; ST6205B and ST6205D were collected two months apart from a 74-year-old Hispanic female pretreated with chemotherapy, four months of niraparib, and seven months of MIRV; STM476 was from a 65-year-old Caucasian female pretreated with chemotherapy, eleven months of rucaparib, and two months of MIRV. We have established and characterized a panel of ovarian XPDX models from patients with clinical resistance to anti-folate receptor therapies. These models can be utilized as a valuable tool in better understanding mechanisms of resistance to FRα-targeting therapies and in developing novel therapies for patients who progress clinically on MIRV or similar..."

Clinical • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • FOLR1 • RB1 • TP53

Engaging an engineered PARP-2 catalytic domain mutant to solve the complex structures harboring approved drugs for structure analyses. (PubMed, Bioorg Chem) - "Consequently, the complex structures of Fluzoparib, Pamiparib, Rucaparib, and Niraparib within PARP-2 were achieved. It suggested that the residues adjacent to Asp766 in the HD and ASL domains and the αJ-αF and ASL-αD interfaces were closely related to the selectivity and trapping mechanism. These results would provide some insights for the design and development of novel PARP-1/2 inhibitors with improved pharmacodynamic properties."

Journal • Oncology • PARP1 • PARP2

Enhancing PARP inhibitor efficacy with CDK12/7/9 degradation in prostate cancer (AACR 2025) - "However, the development of castration-resistant prostate cancer (CRPC) and resistance to AR signaling inhibitors remains a significant clinical challenge.In recent years, the FDA has approved four PARP inhibitors (PARPis) - olaparib, rucaparib, talazoparib, and niraparib - either as monotherapy or in combination with AR signaling inhibitors for CRPC patients carrying deleterious germline or somatic BRCA1/2 mutations or other homologous recombination repair (HRR) gene mutations. In addition, BSJ-5-63 degrades CDK7/9, attenuating AR signaling and further promoting the synthetic lethality of PARP inhibition.Acute CDK12/7/9 degradation by BSJ-5-63 exhibits potent anti-tumor effects in both in vitro and in vivo CRPC models. This study introduces BSJ-5-63 as a promising therapeutic agent that targets both DNA repair and AR signaling pathways, offering potential benefits for a broad patient population."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CDK12 • CDK7 • HRD

Secondary cytoreductive surgery for ovarian cancer recurrence and first-line maintenance therapy: A multicenter retrospective study. (PubMed, Eur J Obstet Gynecol Reprod Biol) - "Complete cytoreduction during secondary surgery for ovarian cancer recurrence is the strongest predictor of prognosis. First-line maintenance therapies do not appear to affect the safety and feasibility of secondary cytoreduction, although they may influence prognosis after secondary surgery."

Journal • Retrospective data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Efficacy and multiomic analysis of Niraparib in relapsed mesothelioma: NERO a randomized phase II trial (AACR 2025) - P2 | "Interferon (IFN) α transcription (9p21.3) but not HRD or DDR gene burden was correlated with sensitivity to PARPi in MIST1, two PDE cohorts (Niraparib and Rucaparib), and in mesothelioma cell lines treated with multiple PARPi's. NERO met its primary endpoint of longer PFS in patients with relapsed mesothelioma. PARPi response is predicted by IFNα transcription and 9p21.3 deletion status. Multiomic analysis of NERO is ongoing and will be presented.NERO is funded by Asthma and Lung UK (MCTA20F2) with drug supplied by GSK.[1] Janes, Alrifai, Fennell N Engl J Med 2021 (385) p1207-1218[2] Fennell et al, Lancet Respir Med 2021 (9) p593-600"

Clinical • Omic analysis • P2 data • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • BRCA1 • BRCA2 • HRD • IFNA1 • MTAP

Evaluating pegylated SN38 (PLX38A) and rucaparib in TP53 wild-type endometrial cancer. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Endometrial Cancer • Oncology • Solid Tumor • TP53

Research Progress of M6A Methylation Modification in Immunotherapy of Colorectal Cancer. (PubMed, Curr Cancer Drug Targets) - "This review has sys-tematically summarized the latest clinical application of six authorized PARPi, including olaparib, rucaparib, niraparib, talazoparib, fuzuloparib and pamiparib, in monotherapy and combination therapies with chemotherapy, radiotherapy, and immunotherapy, in different kinds of cancer. Furthermore, probable challenges in PARPi application and drug resistance mechanisms have also been discussed. Despite these challenges, further development of new PARP1 inhibitors appears promising as a valuable approach to cancer treatment."

Journal • Colorectal Cancer • Oncology • Solid Tumor

Update on PARP inhibitors for the treatment of ovarian cancer. (PubMed, Clin Adv Hematol Oncol) - "Currently, several PARPis are FDA-approved in ovarian cancer: (1) olaparib (BRCAm), niraparib (BRCAm and BRCA wild-type [BRCAwt]), and olaparib/bevacizumab (BRCAm and BRCAwt/HRD) as maintenance therapy after platinum in newly diagnosed advanced disease; and (2) olaparib, niraparib, and rucaparib for recurrent BRCAm platinum-sensitive disease. This review discusses PARPi data in the newly diagnosed and recurrent settings, how current FDA approvals have evolved, and PARPi combination data."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HRD

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology

PARP inhibitors in ovarian cancer: Mechanisms of resistance and implications to therapy. (PubMed, DNA Repair (Amst)) - "Several clinical trials demonstrated that PARPi (olaparib, rucaparib, niraparib) significantly improved progression-free survival (PFS) in HGSOC in the recurrent maintenance setting. Moreover, we explore other innovative treatment strategies aimed at overcoming specific resistance mechanisms, including the inhibition of ATR, WEE1 and POLQ. We also examine the role of PARPi rechallenge in patients with acquired resistance."

Journal • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • HRD • PARP2 • POLQ

Clinical differences among the PARP inhibitors in the first-line treatment of advanced-stage ovarian carcinoma. (PubMed, Expert Rev Anticancer Ther) - "Fortunately, the inclusion of PARP inhibitors (e.g. olaparib, niraparib, and rucaparib) following the completion of primary induction chemotherapy, has conferred improved progression-free survival rates. There are treatment outcome differences among the various PARP inhibitors that coincide with a patient's specific homologous recombination deficit (HRD) status; moreover, only single-agent olaparib and olaparib with bevacizumab have conferred a 5-year overall survival benefit...The inclusion of PARP inhibitors has significantly improved survival benefits in advanced-stage ovarian cancer, especially among patients with an identifiable HRD. While there are tolerability differences inherent to the specific PARP inhibitors, not to mention approval distinctions, olaparib is the only PARP inhibitor that has demonstrated consistent overall survival benefits."

Journal • Oncology • Ovarian Cancer • Solid Tumor • HRD

Targeting Latent HIV Reservoirs: Effectiveness of Combination Therapy with HDAC and PARP Inhibitors. (PubMed, Viruses) - "Latently infected J-Lat cells and dual-fluorescent HIV-infected primary CD4 T cells were treated with the HDAC inhibitor (vorinostat) and one of four PARP inhibitors (olaparib, rucaparib, niraparib, or talazoparib). These findings demonstrate that combining HDAC and PARP inhibitors augments latency reversal and reservoir reduction. With both the HDAC inhibitors and PARP inhibitors used in this study approved by the FDA for cancer treatment, this combination therapy holds strong potential for rapid clinical integration, contingent upon the confirmation of efficacy and safety in ongoing in vivo studies."

Journal • Human Immunodeficiency Virus • Infectious Disease • Oncology • CD4

Development of a homogenous poly(ADP-ribose) assay for screening and profiling PARP inhibitors (AACR 2025) - "Four known PARP1 inhibitors, Olaparib, PJ 34 HCl, Veliparib, and Rucaparib Camsylate, were detected in the bioactive screen and tested in dose response mode with both FP and TR-FRET readout; the measured IC50 values (0.45 nM, 29 nM, 1.4 nM and 0.4 nM, respectively) were consistent with published values. By enabling sensitive, quantitative detection of pADPr formation in a simple, mix-and-read format, the Transcreener pADPr assay should facilitate efforts to develop more effective PARP inhibitors."

Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • BRCA • BRCA1

Clinical and translational results of the academic ARIANES Phase 2 basket study: Longitudinal bulk and single-cell RNAseq analyses of patient tumors identify biological correlates of response to PARP inhibitors and anti-PD-L1 therapy (AACR 2025) - "The academic phase 2 basket trial ARIANES evaluated the PARPi rucaparib (R) and anti-PD-L1 atezolizumab (A) in selected patients (pts). Multi-omics analysis on sequential pts samples reveals that R displays immunomodulatory properties in pt tumors and confirms the potential of (i) R to activate innate immune pathways in tumor cells, and (ii) R + A to induce T-cell activation and clonal expansion. To our knowledge, this is the first study providing a longitudinal and multi-omics bulk/sc resolution analysis of evolution of tumor and immune cells in pts on PARPi and PARPi + anti-PD-L1."

Clinical • IO biomarker • P2 data • Pan tumor • Castration-Resistant Prostate Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • BRCA2 • CCL5 • FANCA • IGF2BP1 • RAD54L • ZBP1

Blocking MDM2 induces downregulation of PARP and enhances apoptosis in SK-N-SH neuroblastoma cells (AACR 2025) - "We hypothesize that MDM2 re-activation by the rebound mechanism of RG-7388 induces PARP degradation in SK-N-SH neuroblastoma cells, possibly through a E3 ligase mediated ubiquitination mechanism that is eventually contributing to enhanced apoptosis. To test this hypothesis, SK-N-SH cells were treated with RG-7388 (2 µM), MDM2 specific E3 ligase inhibitor (10 µM), and iRucaparib-AP6 (10 µM), alone or in combination with RG-7388. Our study results indicate that RG-7388 induces significant downregulation of PARP in the SK-N-SH cells, which was leading to enhanced apoptosis. Furthermore, the results of RG-7388 treatment obtained from SK-N-SH cells confirmed its ability to induce cell death through both p53 activation and downregulation of PARP."

CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • CASP3 • CASP7 • CDKN1A • MDM2 • PARP1

Phase II study of rucaparib and nivolumab in patients with leiomyosarcoma (AACR 2025) - "The combination of ctDNA dynamics with RECIST imaging shows potential for improving the monitoring of patient response and predicting disease progression in LMS. Overall, while the study underscores the limitations of the rucaparib and nivolumab combination, ctDNA appeared to predict early progression and response to therapy and was a useful adjunctive test in cases where the treatment benefit was unclear. Further study is needed to validate these findings."

Clinical • IO biomarker • P2 data • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • BRCA

MSH6 modulates PARP inhibitor sensitivity in BRCA-proficient high-grade serous ovarian cancer (AACR 2025) - "Chemical proteomics with rucaparib showed enrichment of PARP1, PARP2, and associated binding proteins, with notably higher MSH6 levels in sensitive cell lines compared to resistant ones...This study integrates chemical proteomics and ADP-ribosylation analysis to delineate the interplay between PARP1 complex composition and signaling dynamics in PARPi response. Our findings highlight MSH6 and CHAF1A as critical modulators of PARPi sensitivity, providing new insights into resistance mechanisms and identifying potential biomarkers to improve PARPi efficacy in BRCA-proficient HGSOC."

Gynecologic Cancers • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • MSH6 • PARP2

Characterization of PARP inhibitor response in prostate tumor cells reveals drug tolerant persistent phenotype (AACR 2025) - "Characterization of drug tolerant persistence and mechanisms enabling a DTP state under PARP inhibition remain poorly understood in prostate cancer. Viability assays determined efficacious doses of olaparib and rucaparib in PARPi sensitive C4-2B metastatic castration-resistant prostate cancer cells and the C4-2B abiraterone-resistant derivative cells, AbiR. Our data suggest that transient, drug tolerant persistence may mediate survival of a minority of tumor cells via modulating metabolic and immune-associated pathways. Overtime, these persisters may acquire resistance and fuel progression due to increased mutability via down-regulation of DNA repair mechanisms. Future efforts will characterize this phenotype further and investigate vulnerabilities that target survivors to improve treatment efficacy."

Tumor cell • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Intermittent PARP inhibitor regimen in ovarian cancer (IPIROC): A proof-of-concept exploratory pragmatic study (IPIROC#02) using generic rucaparib with pharmacodynamic assessment. (ASCO 2025) - "Clinical Trial Registration Number: KOLGO/IEC/071223-03 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

PK/PD data • Oncology • Ovarian Cancer • Solid Tumor

LODESTAR: A single-arm phase II study of rucaparib in solid tumors with pathogenic germline or somatic variants in homologous recombination repair genes. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT04171700 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

P2 data • Oncology • Solid Tumor • HRD

Association between epigenomic biomarkers and baseline clinical characteristics in patients with mCRPC treated with rucaparib in TRITON2. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT02952534 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Biomarker • Clinical • Castration-Resistant Prostate Cancer • Prostate Cancer