Rucaparib Clinical Development Overview

Rucaparib is an oral, small molecule inhibitor of poly (ADP-ribose) polymerase (PARP)1, 2 and 3 is being developed in multiple tumor types, including ovarian and prostate cancers, as monotherapy and in combination with other anti-cancer agents.  Clovis holds global rights for rucaparib.

Ovarian Cancer

For rucaparib approved or authorized uses click here.

Additional studies enrolling women with ovarian cancer are ongoing or planned:

  • The ARIEL4 Phase 3 confirmatory study in the treatment setting enrolled relapsed ovarian cancer patients with BRCA mutations who have failed two prior lines of therapy and topline data demonstrated that ARIEL4 successfully met the primary endpoint versus chemotherapy; an expanded description the study results will be submitted for presentation at an upcoming medical meeting.
  • The pivotal Phase 3 ATHENA study in first-line maintenance treatment study to evaluate rucaparib + nivolumab, rucaparib, nivolumab and placebo in newly diagnosed patients with stage III/IV high-grade ovarian, fallopian tube or primary peritoneal cancer who have completed platinum-based chemotherapy. In June 2020, the company announced the completion of enrollment of 1000 patients in the Clovis-sponsored Phase 3 ATHENA trial evaluating rucaparib as monotherapy and the combination of rucaparib and nivolumab as front-line maintenance treatment of newly-diagnosed advanced ovarian cancer. ATHENA is the first front-line switch maintenance study designed to evaluate PARP monotherapy and PARP/PD-1 combination therapy in one study design. This Clovis sponsored study is part of a broad clinical collaboration with Bristol Myers Squibb.
  • SEASTAR is a Phase 1b/2 study comprised of multiple single-arm rucaparib combination studies which currently includes the following planned combinations:
    • Rucaparib and lucitanib, Clovis' investigational inhibitor of multiple tyrosine kinases including VEGFR, for the treatment of ovarian cancer, is currently enrolling patients with locally advanced or metastatic solid tumors into the Phase 1b portion.
    • Rucaparib and sacituzumab govitecan, an antibody drug conjugate, for the treatment of advanced metastatic triple-negative breast cancer, relapsed platinum-resistant ovarian cancer and advanced metastatic urothelial cancer. Enrollment is complete for the Phase 1b portion.

Prostate Cancer

Rucaparib is in clinical development for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients.

  • Rucaparib is being studied in the Phase 3 TRITON3 trial for patients with BRCA mutations and ATM mutations who have progressed on AR-targeted therapy and who have not yet received chemo in the castrate-resistant setting. This trial is open for enrollment.
  • The Phase 3 CASPAR study is evaluating the benefit of adding rucaparib to enzalutamide for men with mCRPC that has become resistant to testosterone-deprivation therapy.  This trial is currently planned and is sponsored by the Alliance for Clinical Trials in Oncology which is part of the National Cancer Institute.

Other Studies

The Phase 2 LODESTAR study is a pan-tumor study in patients with solid tumors associated with deleterious mutations in homologous recombination repair genes.

Exploratory studies in other tumor types are also underway. 

Rucaparib Scientific Presentations 

Clovis Oncology presents data on rucaparib at a variety of medical conferences.

Genomic Profiling of Metastatic Castration-Resistant Prostate Cancer Patients for Treatment With Rucaparib: Next-Generation Sequencing of Cell-free Tumor DNA (ctDNA) and Tumor Tissue

Poster Presentation 2020 SUO Virtual Meeting

Clinical Activity of Rucaparib in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) and <i>BRCA1</i> or <i>BRCA2</i> Mutations Identified by FoundationOne® Liquid CDx (F1L CDx)

Virtual Presentation 2020 PCF Scientific Retreat

Timing of adverse events during maintenance treatment with rucaparib for recurrent ovarian cancer in the phase 3 ARIEL3 study

Poster Presentation 2020 ESMO Virtual Meeting

Rucaparib population pharmacokinetics and exposure-response analyses in patients with metastatic castration-resistant prostate cancer (mCRPC) in TRITON2

Poster Presentation 2020 ESMO Virtual Meeting

Rucaparib + sacituzumab govitecan: initial data from the phase 1b/2 SEASTAR study (NCT03992131)

Poster Presentation 2020 ESMO Virtual Meeting

Postprogression Efficacy Outcomes From the Phase 3 ARIEL3 Study of Rucaparib in Patients With Platinum-Sensitive Recurrent Ovarian Carcinoma Associated With Either <i>BRCA1</i> or <i>BRCA2</i> Mutations

Virtual Presentation 2020 ICGS Digital Annual Global Meeting​

Evaluation of Brain Pharmacokinetics (PK) and Tumor Growth Inhibition of PARP Inhibitors in Mouse Xenograft Models Using Semi-Mechanistic PK/Pharmacodynamic (PD) Modeling

Poster Presentation 2020 AACR Virtual Meeting II

Characterization of Patients With Long-term Responses to Rucaparib in Recurrent Ovarian Cancer

Virtual Presentation 2020 ASCO

Postprogression Outcomes in Patients With Ovarian Carcinoma Associated With a Mutation in a Non-<i>BRCA</i> Homologous Recombination Repair Gene Receiving Rucaparib Maintenance Treatment: Results From the Phase 3 Study ARIEL3

Webinar Presentation 2020 SGO

Population Exposure-Safety and Exposure-Efficacy Analyses for Rucaparib in Patients With Recurrent Ovarian Carcinoma From Study 10 and ARIEL2

Poster Presentation 2020 SGO

Rucaparib for recurrent, locally advanced or metastatic urothelial carcinoma: results from ATLAS, a phase 2, open-label trial

Presented at 2020 ASCO GU

Genomic characteristics associated with clinical activity of rucaparib in patients (pts) with <i>BRCA1</i> or <i>BRCA2</i> (<i>BRCA</i>)-mutated metastatic castration-resistant prostate cancer (mCRPC)

Presented at 2020 ASCO GU