Frontline PARP Maintenance Study in Advanced Ovarian Cancer Ready to Start Treatment

Target enrollment has been completed for the phase 3 ATHENA trial, which will evaluate rucaparib (Rubraca) as frontline maintenance therapy in patients with newly diagnosed advanced ovarian cancer, announced Clovis Oncology. Data from the trial is expected in 2021.

This is the first frontline switch maintenance therapy trial that is designed to show PARP inhibitor monotherapy and PARP in combination with anti-PD-1 agents in 1 study design.

“The completion of target patient enrollment in the Phase 3 ATHENA trial is an important milestone for Clovis and a critical step toward developing additional therapeutic options for women with advanced ovarian cancer,” said Patrick J. Mahaffy, president, and chief executive officer, Clovis Oncology, in a statement. “This was a tremendous effort by trial investigators, our collaborators, and our dedicated Clovis team to complete target enrollment in this 1000-patient study in under two years. Most important, we are grateful to all of the patients who participated in this study.”

The PARP inhibitor rucaparib as monotherapy had previously received FDA approval as a maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer after achieving a complete or partial response to platinum-based chemotherapy. ATHENA will also evaluate rucaparib in combination with nivolumab (Opdivo), the PD-1 inhibitor, and nivolumab alone.

The target enrollment was 1000 patients, which were enrolled across clinical trial centers in 24 countries throughout North America, Europe, and Asia. The multinational, double-blind, placebo-controlled study will randomize patients to 1 of 4 different treatment arms. The objective of the study is to analyze the responses to treatment based on homologous recombination deficiency (HRD) status of tumor samples.

In arm A, patients will receive oral rucaparib twice daily plus intravenous (IV) nivolumab once every 4 weeks. Arm B will receive oral rucaparib twice daily with an IV placebo once every 4 weeks. Nivolumab will be administered once every 4 weeks in arm C with an oral placebo twice daily. Finally, in arm D, patients will receive an oral placebo tablet twice daily plus an IV placebo once every 4 weeks.

The primary end point of the study is investigator-assessed progression-free survival (PFS), and secondary end points include PFS by blinded independent central review, overall survival, objective response rate, duration of response, number of patients with treatment-emergent adverse events (AEs), number of patients with serious AEs, and number of patients with laboratory abnormalities as a measure of safety and tolerability.

Two prospectively defined molecular sub-groups will be evaluated in the primary efficacy analysis in a step-down manner. The first group included HRD-positive patients and those with BRCA mutations. The second group will be the intent-to-treat population, which is all patients treated in the study.

To be included in the ATHENA study, patients 18 years or older had to have newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer and have completed cytoreductive surgery. Patients also had to have completed first-line platinum-based chemotherapy and surgery and achieved a response. They also needed an ECOG performance status of 0 or 1 and sufficient tumor tissue for the planned analysis.

Patients were excluded if they had pure sarcomas or borderline tumors or mucinous tumors, an active second malignancy, known central nervous system brain metastases, or any prior treatment for ovarian cancer other than the first-line chemotherapy regimen. They were also excluded from the study if they had evidence of interstitial lung disease, active pneumonitis, active/know/suspected autoimmune disease, or a condition that requires active systemic treatment with corticosteroids or other immunosuppressive medications.

Topline data from arm B are expected in the second half of 2021. If these data are supportive, they would serve as the basis of a supplemental New Drug Application (sNDA) for rucaparib as frontline maintenance therapy for patients with newly diagnosed advanced ovarian cancer.

The topline data for the combination of rucaparib and nivolumab versus rucaparib monotherapy are expected about a year or more later than the monotherapy readout, which could potentially serve as the bases of an sNDA for the combination in the frontline treatment of newly-diagnosed ovarian cancer if the data are supportive.

Two prospectively defined molecular sub-groups will be evaluated in the primary efficacy analysis in a step-down manner. The first group included HRD-positive patients and those with BRCA mutations. The second group will be the intent-to-treat population, which is all patients treated in the study.

_Reference

_{Clovis oncology announces completion of target enrollment in the ATHENA trial, a phase 3 maintenance treatment study in front-line, newly-diagnosed advanced ovarian cancer. News Release. Boulder, CO: Clovis Oncology; June 10, 2020. Accessed June 11, 2020. https://bit.ly/3ffRjg1}