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

Rucaparib for the Treatment of Metastatic Castration-resistant Prostate Cancer Associated with a DNA Damage Repair Gene Alteration: Final Results from the Phase 2 TRITON2 Study. (PubMed, Eur Urol) - P2 | "The final TRITON2 results confirm the clinical benefit and manageable safety profile of rucaparib in patients with mCRPC, including those with an alteration in BRCA or select non-BRCA DDR gene."

Journal • Metastases • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • CDK12 • CHEK2 • PALB2

A phase Ib, open-label study evaluating the safety and efficacy of ipatasertib plus rucaparib in patients with metastatic castration-resistant prostate cancer. (PubMed, Clin Cancer Res) - P1 | "Ipatasertib plus rucaparib was manageable with dose modification but did not demonstrate synergistic or additive antitumor activity in previously treated patients with mCRPC."

Journal • Metastases • Genito-urinary Cancer • Hematological Disorders • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor

Rucaparib or Physician's Choice in Metastatic Prostate Cancer. (PubMed, N Engl J Med) - P3 | "The duration of imaging-based progression-free survival was significantly longer with rucaparib than with a control medication among patients who had metastatic, castration-resistant prostate cancer with a BRCA alteration. (Funded by Clovis Oncology; TRITON3 ClinicalTrials.gov number, NCT02975934.)."

Journal • Metastases • Fatigue • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ATM • BRCA • BRCA1 • BRCA2

Heterocyclic Scaffolds in PARP-1 Inhibition: An Emerging Strategy for Targeted Anticancer Therapy. (PubMed, Mini Rev Med Chem) - "Heterocyclic scaffolds offer a promising route toward next-generation PARP-1 inhibitors with enhanced efficacy, reduced resistance, and optimized safety, supporting personalized anticancer therapy."

Journal • Hematological Disorders • Oncology • BRCA • HRD • PARP2

Rucaparib vs docetaxel or second-generation androgen receptor pathway inhibitor therapy for metastatic castration-resistant prostate cancer patients with BRCA mutations with or without liver metastases in TRITON3 (AUA 2025) - P3 | "In TRITON3, rucaparib provided a numerically longer rPFS, higher ORR, and similar OS in comparison with physician's choice for pts with BRCA-mutated mCRPC with or without liver mets, supporting rucaparib as a treatment option. These results should be interpreted with caution owing to the small number of pts with liver mets."

Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA

A Randomized, Double-Blind, Biomarker-Selected, Phase II Clinical Trial of Maintenance Poly ADP-Ribose Polymerase Inhibition With Rucaparib Following Chemotherapy for Metastatic Urothelial Carcinoma. (PubMed, J Clin Oncol) - "Maintenance rucaparib, following platinum-based chemotherapy, extended PFS in DRD biomarker-selected patients with mUC and was tolerable. Further investigation of poly ADP-ribose polymerase inhibition in selected patients with mUC is warranted."

Biomarker • Clinical • Journal • P2 data • Fatigue • Oncology • Solid Tumor • Urothelial Cancer • DRD

A phase II, randomized, double-blind study of the use of rucaparib vs. placebo maintenance therapy in metastatic and recurrent endometrial cancer. (PubMed, Gynecol Oncol) - P2 | "Maintenance use of rucaparib after first- or second-line chemotherapy demonstrates promising activity and warrants further evaluation in a phase III evaluation. Adverse events were aligned with previous use of rucaparib in other tumor types and no new safety signals were identified."

Clinical • Journal • P2 data • P53mut • Endometrial Cancer • Fatigue • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • TP53

Integrative proteomics reveals MSH6 to modulate PARP inhibitor sensitivity in BRCA1/2-proficient ovarian cancer. (PubMed, PLoS One) - "Chemical proteomics with rucaparib revealed different PARP1 complexes including higher enrichment of MSH6 in sensitive cells...In conclusion, this study identifies the PARP1-MSH6 interaction to modulate PARPi sensitivity via CHAF1A-mTOR signaling in BRCA-proficient ovarian cancer. By integrating chemical proteomics and ADP-ribosylation proteomics, we delineate the interplay between PARP1 complex composition and signaling dynamics, highlighting MSH6 as a critical modulator of PARPi response and potential biomarker to enhance therapeutic efficacy in BRCA-proficient HGSOC."

Journal • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • MSH6 • PARP2

A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). (PubMed, J Clin Oncol) - P3 | "Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD."

Journal • Monotherapy • P3 data • Hematological Disorders • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2

BrUOG360: A phase Ib/II study of copanlisib combined with rucaparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2022) - P1/2 | " Enrollment criteria included progressive mCRPC, prior androgen inhibitors (abiraterone, enzalutamide, and/or apalutamide); prior taxane chemotherapy was allowed...Seven pts (63%) received prior chemotherapy (docetaxel [7], cabazitaxel [3])... The combination of rucaparib and copanlisib is well tolerated. The RP2D was rucaparib 400mg BID with copanlisib 45mg (D1, D15; 28-day cycle) with signal of efficacy. Enrollment in a phase 2 expansion cohort in HR-mutated mCRPC is ongoing."

Clinical • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CDK12 • FANCA • PALB2

PATIENTS WITH NEWLY DIAGNOSED ADVANCED OVARIAN CANCER IN ATHENA-MONO/GOG-3020/ENGOT-OV45: SUBSEQUENT ANTI-CANCER THERAPY BY HRD STATUS (IGCS 2026) - "The data cutoff was 5 May 2025. In the ITT, 26% of patients (111/427) receiving rucaparib and 14% (16/111) receiving placebo remained in long -term follow -up without receiving any ST. In the HRD -positive and HRD -negative subgroups, a higher percentage of ST were administered to patients receiving placebo than rucaparib (Table 1)."

Clinical • Metastases • Oncology • Ovarian Cancer • Solid Tumor • HRD

A phase II, randomized, double-blind study of the use of rucaparib versus placebo maintenance therapy in metastatic and recurrent endometrial cancer (SGO 2024) - "Maintenance use of rucaparib after first or second line chemotherapy improves PFS for patients with metastatic and recurrent endometrial cancer in a statistically significant and clinically impactful manner."

Clinical • Late-breaking abstract • Metastases • P2 data • Endometrial Cancer • Oncology • Solid Tumor • BRCA • DRD

Updated progression-free survival (PFS) in patients (pts) with newly diagnosed advanced ovarian cancer (OC) treated with rucaparib (RUC) in ATHENA-MONO (ESMO-GC 2024) - P3 | "RUC maintained a clinically significant improvement in PFS with 4.0 y of follow-up in pts with newly diagnosed advanced OC in pts with both low and high risk of progression. No new safety signals were identified."

Clinical • Metastases • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Ovarian Cancer • Solid Tumor • HRD

A descriptive study on the treatment and outcomes of patients with platinum-sensitive, advanced, BRCA- or PALB2-related pancreatic cancer who have progressed on rucaparib. (ASCO 2022) - "Of these, 22 received second-line chemotherapy: nine were treated with an oxaliplatin-based regimen, nine were treated with a cisplatin-based regimen, and four were treated with non-platinum regimens. In this small sample of patients with advanced pancreatic cancer with progressive disease on PARPi, chemotherapy retains some activity. Further study to identify predictors of response and/or resistance to post-PARPi treatment are underway. >OS is defined from study enrollment until death."

Clinical • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • PALB2

Emergence of BRCA Reversion Mutations in Patients with Metastatic Castration-resistant Prostate Cancer After Treatment with Rucaparib. (PubMed, Eur Urol) - "These findings suggest that BRCA reversion mutations are a significant mechanism of acquired resistance to rucaparib in patients with BRCA+ mCRPC, with evidence of subclonal convergence promoting systemic resistance."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • BRCA • BRCA1 • BRCA2 • CAST

ATHENA–MONO (GOG-3020/ENGOT-ov45): A randomized, double-blind, phase 3 trial evaluating rucaparib monotherapy versus placebo as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer. (ASCO 2022) - P3 | " Pts with stage III–IV high-grade OC who had completed cytoreductive surgery (R0 permitted) and 4–8 cycles of 1L platinum-doublet (bevacizumab allowed with chemotherapy) with a response were randomized 4:1 to oral rucaparib 600 mg BID or placebo. Rucaparib monotherapy is effective as 1L maintenance with significant benefit vs placebo observed in the ITT and HRD populations, as well as the non-nested subgroup of pts without known HRD."

Clinical • Late-breaking abstract • Monotherapy • P3 data • Anemia • Hematological Disorders • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • BRCA

Safety of rucaparib vs docetaxel or second-generation androgen receptor pathway inhibitor therapy for patients with metastatic castration-resistant prostate cancer and a BRCA mutation in TRITON3 (AUA 2026) - P3 | " In TRITON3, patients with disease progression after 1 prior second-generation ARPI in any setting were randomized 2:1 to rucaparib 600 mg BID or physician's choice of docetaxel or ARPI (abiraterone acetate or enzalutamide). Rucaparib has a manageable and consistent safety profile in patients with BRCA-mutated prostate cancer in TRITON3. There was a low rate of discontinuation due to TEAEs suggesting that supportive care and dose adjustments are effective strategies for mitigating TEAEs."

Clinical • Metastases • Acute Myelogenous Leukemia • Castration-Resistant Prostate Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Prostate Cancer • Solid Tumor • BRCA

ATHENA-COMBO, a phase III, randomized trial comparing rucaparib (RUCA) + nivolumab (NIVO) combination therapy vs RUCA monotherapy as maintenance treatment in patients (pts) with newly diagnosed ovarian cancer (OC) (ESMO 2024) - P3 | "NIVO in combination with RUCA did not add to the PFS benefit of RUCA observed in MONO. The safety profile of RUCA in combination with NIVO was consistent with previously reported studies and their individually known safety profiles."

Clinical • Combination therapy • Late-breaking abstract • Monotherapy • P3 data • Gynecologic Cancers • Oncology • Ovarian Cancer • HRD • PD-L1

Optimized dose schedule of rucaparib and liposomal irinotecan/5-fluorouracil in metastatic gastrointestinal cancers: A phase 1 study. (PubMed, Cancer) - "This optimized dosing schedule successfully established the MTD for RUB with nal-IRI and 5-FU, overcoming prior challenges with PARP inhibitor and irinotecan combinations. The promising ORR and DCR support further evaluation of this regimen in advanced GI malignancies."

Journal • P1 data • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • ATM • BRCA • HRD

Efficacy and safety of rucaparib maintenance treatment in patients from ATHENA-MONO/GOG-3020/ENGOT-ov45 with newly diagnosed advanced ovarian cancer not associated with homologous recombination deficiency (ESMO-GC 2025) - P3 | "Methods Patients with stage III–IV high-grade ovarian cancer who underwent cytoreductive surgery (R0 permitted) and 4–8 cycles of first-line platinum-doublet chemotherapy (bevacizumab allowed with chemotherapy) with a response were randomized 4:1 to oral rucaparib 600 mg BID or placebo. Legal entity responsible for the study Clovis Oncology, Inc. and pharma& GmbH."

Clinical • Metastases • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HRD • MUC16

TRIUMPH: phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline homologous recombination repair gene mutations. (PubMed, Oncologist) - P2 | "Rucaparib can induce clinical responses in a biomarker-selected metastatic prostate cancer population without concurrent ADT. However, the pre-specified efficacy threshold was not met, and enrolment was truncated. Although durable responses were observed in a subset of patients, further study of PARPi treatment without ADT in mHSPC is unlikely to change clinical practice."

Journal • Metastases • Monotherapy • P2 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CHEK2 • HRD

BrUOG360: A phase Ib/II study of copanlisib combined with rucaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) (AACR 2023) - P1/2 | "We describe preliminary results of a phase Ib/II study investigating safety of the combination of copanlisib (pan-class I PI3Ki) and rucaparib (PARP-1, -2 and -3 inhibitor). Enrollment criteria included progressive mCRPC, prior androgen inhibitors (abiraterone, enzalutamide, and/or apalutamide); prior taxane chemotherapy was allowed...Nine patients (69%) received prior chemotherapy (docetaxel [6], cabazitaxel [3])... The combination of rucaparib and copanlisib is well tolerated. The RP2D was rucaparib 400mg BID with copanlisib 45mg (D1, D15; 28-day cycle) with signal of efficacy in patients with and without HRD. Clinical trial information: NCT04253262."

Clinical • Metastases • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CDK12 • FANCA • PALB2

Rucaparib versus chemotherapy for treatment of relapsed ovarian cancer with deleterious BRCA1 or BRCA2 mutation (ARIEL4): final results of an international, open-label, randomised, phase 3 trial. (PubMed, Lancet Oncol) - P3 | "These data highlight the need for a better understanding of the most appropriate treatment for patients who have progressed on a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, and the optimal sequencing of chemotherapy and PARP inhibitors in advanced ovarian cancer."

Clinical • Journal • P3 data • Cardiovascular • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2

Rucaparib for metastatic castration-resistant prostate cancer (mCRPC): TRITON3 interim overall survival and efficacy of rucaparib vs docetaxel or second-generation androgen pathway inhibitor therapy. (ASCO-GU 2023) - P3 | "Background: TRITON3 (NCT02975934) is a randomized, multicenter, open-label, phase 3 study of rucaparib vs physician’s choice (docetaxel [DTX], abiraterone [ABI] or enzalutamide [ENZ]) in patients (pts) with chemotherapy-naïve mCRPC with BRCA1/2 (BRCA) or ATM alterations. Rucaparib significantly improved rPFS vs either DTX or ABI/ENZ; safety was consistent with prior reports. Interim OS results suggest a trend towards improvement for rucaparib vs DTX or ABI/ENZ in pts with mCRPC and BRCA alterations. Clinical trial information: NCT02975934."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ATM • BRCA • BRCA1 • BRCA2

TRIUMPH: Phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline DNA repair gene mutations. (ASCO-GU 2023) - P2 | "Rucaparib can induce clinical responses in a biomarker-selected PCa population without concurrent ADT. However, the pre-specified threshold of PSA50 response was not met. Although durable responses were observed in a subset of pts, PARPi without ADT in metastatic hormone sensitive PCa will not be pursued."

Clinical • Metastases • Monotherapy • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CHEK2