Applications Submitted to FDA and EMA for Maintenance Rucaparib in Advanced Ovarian Cancer


A supplement biologics license and a Type II variation were submitted to the FDA and European Medicines Agency, respectively, for first-line rucaparib in patients with advanced ovarian cancer.

A supplemental new drug application has been submitted to the FDA and a Type II variation to the European Medicines Agency for rucaparib (Rubraca) as first-line maintenance treatment in patients with advanced ovarian cancer regardless biomarker status and following response to first-line platinum-based chemotherapy, according to a press release from Clovis Oncology.1

Results from the phase 3 ATHENA-MONO trial (NCT03522246) led to the submission, the results of which were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.2 In the intent-to-treat (ITT) population, the median progression-free survival (PFS) in the rucaparib group was 20.2 months (95% CI, 15.2-24.7) vs 9.2 months (95% CI, 8.3-12.2) in the placebo arm (HR, 0.52; 95% CI, 0.40-0.68; log-rank P <.0001). Median PFS by blind-independent central radiology review (BICR) was 25.9 months (95% CI, 16.8-not reached [NR]) in the rucaparib arm and 9.1 months (95% CI, 6.4-9.7) in the placebo arm (HR, 0.47; 95% CI, 0.36-0.63; log-rank P <.0001).

“We believe the compelling PFS 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,” Patrick J. Mahaffy, president and chief executive officer of Clovis Oncology, said in the press release. “We are grateful to the patients who participated in the trial and for the support of the clinical community familiar with these results.”

A total of 538 patients with high-grade ovarian, fallopian tube, or primary peritoneal cancer enrolled on the study. Of note, patients were randomly assigned 4:4:1:1 to 1 of 4 different treatment arms. These cohorts included arm A, which received rucaparib at 600 mg twice daily plus intravenous nivolumab (Opdivo) at 480 mg; arm B which received intravenous placebo and rucaparib; arm C which received oral placebo and nivolumab; and arm D which received intravenous and oral placebo regimen. The ATHENA-MONO trial included findings from arms B and D.

For patients in the homologous recombination deficiency (HRD) group, the investigator-assessed median PFS was 28.7 months (95% CI, 23.0-NR) in the rucaparib group vs 11.3 months (95% CI, 9.1-22.1) in the placebo group (HR, 0.47; 95% CI, 0.31-0.72; P = .0004). Additionally, the median PFS via BICR not NR (95% CI, 28.7-NR) in the rucaparib group compared with 9.9 months (95% CI, 6.5-NR) in the placebo group (HR, 0.44; 95% CI, 0.28-0.70; P = .0004).

Objective response rate (ORR) was assessed in the HRD group and was 58.8% (95% CI, 32.9%-81.6%) in the rucaparib arm vs 20.0% (95% CI, 0.5%-71.6%) in the placebo arm. In this population, it was comprised exclusively of partial responses, with a median duration of response (DOR) of 16.7 vs 5.5 months in both respective groups. In the intent-to-treat group, the ORR was 48.8% (95% CI, 32.9%-64.9%) in the rucaparib group vs 9.1% (95% CI, 0.2%-41.3%) in the placebo arm. One complete response was observed in the experimental cohort. Additionally, the median DOR was 22.1 months in the rucaparib group vs 5.5 months in the placebo group.

Adverse effects (AEs) of grade 3 or higher included anemia or increased hemoglobin (28.7% vs 0.0%), neutropenia or neutrophil count decrease (14.6% vs 0.9%), and increased alanine aminotransferase or aspartate aminotransferase (10.6% vs 0.9%) in the rucaparib and placebo groups, respectively.

As of the data cutoff on March 23, 2022, 12.4% of patients in the rucaparib arm vs 9.9% in the placebo arm were still on treatments, with 63.5% vs 80.2% discontinuing before 2 years due to disease progression (41.0% vs 64.9%), AEs (12.6% vs 5.4%), withdrawal of consent (4.9% vs 2.7%), clinical progression (3.3% vs 5.4%), or other reasons (1.6% vs 1.8%). In the rucaparib group, the median treatment duration was 14.7 months (95% CI, 0.1-32.7) vs 9.9 months (95% CI, 0.9-25.9) in the placebo group. The median duration of follow-up was 26.1 months (95% CI, 25.8-26.9) in the rucaparib group vs 26.2 months (95% CI, 24.0-27.7) in the placebo group.


  1. Clovis Oncology submits application for Rubraca label expansion in the US and European Union as first-line maintenance treatment in women with advanced ovarian cancer. News Release. Clovis Oncology. September 13, 2022. Accessed September 14, 2022.
  2. Monk BJ, Parkinson C, Lim MC, et al. 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. J Clin Oncol. 2022;40(suppl 17):LBA5500. doi:10.1200/JCO.2022.40.17_suppl.LBA5500

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