The pivotal phase 3 ATHENA trial, which will examine the safety and efficacy of rucaparib in combination with nivolumab as maintenance treatment following response to front-line platinum-based chemotherapy in patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, has completed target enrollment.
The pivotal phase 3 ATHENA trial (NCT03522246), which will examine the safety and efficacy of rucaparib (Rubraca) in combination with nivolumab (Opdivo) as maintenance treatment following response to front-line platinum-based chemotherapy in patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, has completed target enrollment, according to an announcement from Clovis Oncology.1
The target enrollment for the ATHENA trial was approximately 1000 patients with ovarian cancer. Participants were enrolled at clinical trial centers in 24 countries across North America, Europe, and Asia.
“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,” Patrick J. Mahaffy, president and chief executive officer of Clovis Oncology, stated in a recent press release. “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 2 years. Most important, we are grateful to all of the patients who participated in this study.”
In the randomized, double-blind, placebo-controlled, 4-arm, phase 3 trial is the first to show PARP monotherapy and a PARP/PD-1 combination in a single study design. Arm A will receive oral rucaparib administered twice daily and intravenous (IV) nivolumab once every 4 weeks. Those in arm B will receive oral rucaparib twice daily and IV placebo once every 4 weeks. Arm C will receive an oral placebo twice daily and IV nivolumab once every 4 weeks. Arm D will receive an oral placebo twice daily and an IV placebo once every 4 weeks.2
To be eligible for enrollment on the trial, patients 18 years of age or older must have newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients also had to have a completed cytoreductive surgery, either before chemotherapy or following neoadjuvant chemotherapy and have completed first-line platinum-based chemotherapy and surgery and responded. Patients must also have an ECOG performance status of 0 or 1 to participate. Patients with sarcomas, borderline tumors or mucinous tumors, active second malignancies; central nervous system brain metastases, evidence indicating interstitial lung disease, and those who received any other previous treatment other than the frontline platinum regimen are not permitted.
The primary end point of the trial is investigator assessed progression-free survival (PFS) from randomization until disease progression. Key secondary end points include PFS per blinded independent central review, overall survival, objective response rate, duration of response, and safety. Response to treatment will be evaluated based on homologous recombination status of tumor samples.3
Topline data for the rucaparib monotherapy versus placebo arm in all populations is anticipated in the second half of 2021. If positive, the data will support a supplemental new drug application (sNDA) for the agent as a maintenance treatment in first-line newly diagnosed advanced ovarian cancer. The combination of rucaparib plus nivolumab versus rucaparib monotherapy in all populations are anticipated 1 year or more. If positive, the data will serve as the basis of a sNDA for the combination in the first-line treatment of patients with newly diagnosed ovarian cancer.
For both, the primary efficacy analysis will examine 2 prospectively defined molecular subgroups in a step-down manner. Investigators will first evaluate homologous recombination deficiency–positive patients, such as those with BRCA mutations. They will also examine the intent-to-treat population or all patients enrolled on ATHENA.
Previous findings presented during the 2018 AACR Annual Meeting showed that rucaparib, when paired with an anti-PD1 or anti–PD-L1 in a BRCA-/- syngeneic ovarian cancer model, inhibited tumor growth in mice by 110%.3 Mice that were given the combination of rucaparib plus anti–PD-1 had a median survival of over 125 days versus just 83 days with an anti–PD-1 agent alone. Additionally, 100% of mice (n = 13/13) that received rucaparib and an anti–PD-L1 were tumor free at day 125 versus just 5 of 15 with an anti–PD-L1 agent alone.
In April 2018, the FDA approved rucaparib as a maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy, based on data from the phase 3 ARIEL3 trial. The agent is also indicated for adult patients with deleterious BRCA mutation–positive epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with 2 or more chemotherapies. Rucaparib also has an indication in prostate cancer.