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Large Phase III ATHENA Trial of Rucaparib/Nivolumab Combo in Ovarian Cancer Now Enrolling

Lisa Astor
Published Online:9:09 PM, Wed August 8, 2018

Brad Monk, MD

The first patient has been enrolled in the phase III ATHENA trial looking at rucaparib (Rubraca) in combination with nivolumab (Opdivo) in patients with newly diagnosed advanced ovarian cancer, according to Clovis Oncology, the company developing rucaparib.

The multinational, randomized, double-blind, placebo-controlled trial is being conducted in association with the Gynecologic Oncology Group (GOG) and the European Network for Gynecological Oncological Trials (ENGOT) group.

“I am pleased the GOG and ENGOT are conducting the first trial designed to investigate whether the combination of a PARP inhibitor and PD-1 blocking antibody can demonstrate not only an improvement in progression-free survival in the first-line maintenance setting for women with advanced ovarian cancer, but also whether the combination can change the natural course of the disease by delaying or reducing recurrence following frontline therapy,” said lead investigator Brad Monk, MD, professor of gynecologic oncology at University of Arizona and Creighton University, medical director of the US Oncology Research Gynecology Program in Phoenix, Arizona.

ATHENA will consist of 4 arms looking at the combination of rucaparib and nivolumab as a maintenance therapy following a response to a frontline platinum-based chemotherapy regimen (NCT03522246). The combination will be compared with rucaparib plus placebo, nivolumab plus placebo, and placebo alone.

In the treatment arms containing nivolumab, the PD-1 inhibitor will be administered intravenously once every 4 weeks, and rucaparib, when used, will be given orally twice daily. Patients will be treated until disease progression.

“Rubraca combination trials such as ATHENA are encouraging to see, because the possible implications are particularly meaningful for women with advanced ovarian cancer, who need a wide range of treatment options,” said Rebecca Kristeleit, BSc, MBChB, MRCP, PhD, clinical senior lecturer and consultant medical oncologist, University College London, and UK and ATHENA ENGOT/non-US lead investigator, in a statement. “The participation by the GOG and the ENGOT in the evaluation of a PARP inhibitor in combination with a PD-1 agent reflects the interest around this approach.”

Patients eligible for enrollment in the ATHENA trial include patients with newly diagnosed FIGO stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer who have complemented adjuvant or neoadjuvant chemotherapy and cytoreductive surgery and achieved a response to treatment. Exclusion criteria include autoimmune diseases, brain metastases, conditions requiring use of immunosuppressive treatments, and secondary malignancies. Approximately 1000 patients with ovarian cancer are expected to be enrolled in the study at clinical trial centers in the United States and internationally.

The primary endpoint of the trial is investigator-assessed progression-free survival (PFS), and key secondary endpoints include PFS by blinded independent central review, overall survival, objective response rate, duration of response, and safety. Responses will also be analyzed based on homologous recombination status.

Rucaparib was approved by the FDA in April 2018 as a maintenance therapy 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 the results of the phase III ARIEL3 trial.1 In the trial, the median PFS with the PARP inhibitor was 10.8 months compared with 5.4 months with placebo, and among patients with germline or somatic BRCA mutations, the median PFS with rucaparib was 16.6 months. Among patients with homologous recombination deficiency, the median PFS was 13.6 months versus 5.4 months with placebo.

As a single agent, nivolumab has demonstrated activity in treating patients with platinum-resistant ovarian cancer with responses seen in 15% of patients in a small study.2
The ATHENA trial is one of several studies currently exploring the potential for checkpoint inhibition in combination with PARP inhibition.
  1. Ledermann J, Oza AM, Lorusso D, et al. ARIEL3: a phase 3, randomised, double-blind study of rucaparib vs placebo following response to platinum-based chemotherapy for recurrent ovarian carcinoma (OC). Presented at: 2017 ESMO Congress; September 8-12; Madrid, Spain. Abstract LBA40_PR.
  2. Hamanishi J, Mandai M, Ikeda T, et al. Safety and antitumor activity of anti–PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2015;33(34):4015-4022. doi: 10.1200/JCO.2015.62.3397.

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