Clovis Oncology Submits New Drug Application for Rucaparib as First-Line Maintenance Treatment for Advanced Ovarian Cancer

Clovis Oncology, Inc has submitted a supplemental New Drug Application (sNDA) to the FDA for rucaparib (Rubraca) as first-line maintenance treatment for patients with advanced ovarian cancer, regardless of biomarker status. Rucaparib was also submitted as a Type II variation with the European Medicines Agency.

Rucaparib can also be used in patients who already responded to first-line platinum-based chemotherapy. Although rucaparib is not currently approved as a first-line treatment for ovarian cancer, the data show that rucaprarib lowered the risk of disease progression by 53% compared to placebo.

“We believe the compelling PFS (progression-free survival) results, the primary endpoint of the ATHENA-MONO trial, are strongly supportive of an approval and reinforce the potential of Rubraca as an important new first-line maintenance treatment for ovarian cancer,” said Patrick J. Mahaffy, president and CEO of Clovis Oncology, in a recent press release.

Rucaparib is a small molecule inhibitor of PARP1, PARP2, and PARP3 that is being developed as a monotherapy treatment or to in combination with other anti-cancer treatments for multiple cancer types, including ovarian cancer.

The phase 3 ATHENA-MONO trial analyzed the safety and efficacy of rucaparib vs placebo among multiple populations with a primary endpoint of PFS by investigator review.

Researchers identified 538 patients with high-grade ovarian, primary peritoneal, or fallopian tube cancer identified for the ATHENA-MONO trial. Participants were divided into 2 prospectively defined molecular populations in a step-down manner, which were homologous recombination deficiency (HRD)-positive inclusive of BRCAm tumors and BRCAwt/LOH high tumors, and all patients randomized in the intent-to-treat (ITT) population in the trial.

The investigators found that the patients in both cohorts had significantly improved PFS, regardless of biomarker status. HRD participants on rucaparib experienced a median PFS of 28.7 months compared with an 11.3-month median PFS in the placebo group.

Rucaparib also produced a median PFS of 20.2 months among the ITT population. This was more than 2-times the PFS of the ITT placebo group (median PFS 9.2 months). Rucaparib reduced the risk of disease progression by 48% among ITT patients.

Researchers also analyzed PFS by first-line chemotherapy response. According to the study, patients treated with rucaparib as maintenance therapy showed benefit among all subgroups when evaluated against response per RECIST v1.1 at any time during first-line chemotherapy.

Among HRD-positive patients, those who demonstrated a partial response to first-line chemotherapy and who received rucaparib had a median PFS of 14.8 months versus 9.1 months in the placebo arm. Patients who demonstrated a complete response to first-line chemotherapy achieved a median PFS of 25.8 months with rucaparib, whereas the median PFS was not reached for patients in the placebo arm.

The ATHENA-MONO study showed that rucaparib has a safety profile consistent with current labels in both the United States and Europe. In 2% or more of participants, the most common grade 3 or greater adverse events (TEAEs) were anemia, neutropenia, increased ALT/AST, thrombocytopenia, asthenia, and leukopenia.

Clovis CEO Mahaffy concluded in the press release that “We are grateful to the patients who participated in the trial and for the support of the clinical community familiar with these results.”

Reference

Clovis Oncology, Inc. Clovis Oncology Submits Applications For Rubraca® Label Expansion In The US And European Union As First-Line Maintenance Treatment In Women With Advanced Ovarian Cancer. Clovis Oncology website. September 13, 2022. Accessed on September 13, 2022. https://ir.clovisoncology.com/investors-and-news/news-releases/press-release-details/2022/Clovis-Oncology-Submits-Applications-for-Rubraca-Label-Expansion-in-the-US-and-European-Union-as-First-line-Maintenance-Treatment-in-Women-with-Advanced-Ovarian-Cancer/default.aspx