Safety Data Supports Rucaparib With Nivolumab, Ipilimumab Moving to Phase 2 Trial for Replaced Ovarian Cancer

Rucaparib at the 400 mg dosage combined with nivolumab and ipilimumab for 4 cycles will continue onto a phase 2 trial for individuals with relapsed ovarian cancer (ROC), according to a presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. In the CeNturIOn trial, investigators enrolled eligible individuals who had received 1 or more, but less than 3, lines of chemotherapy for between 3 months to a year from their last platinum chemotherapy, with only 1 patient who could experience a dose limiting toxicity over the initial 6 weeks of treatment.

During the study, the patients were given nivolumab at the 240 mg strength daily for 14 days, ipilimumab at the 1 mg/kg strength daily for 42 days intravenously for up to 12 months, and rucaparib orally at the 600 mg strength twice a day, continuously. Additionally, all but 1 of the 7 patients received nivolumab and ipilimumab to meet the dose limiting toxicity evaluability, but 5 of those 6 received less than 43% of rucaparib during the safety period.

Six other individuals were recruited who had received 60% or greater starting dose of rucaparib in the first 6 weeks are now required for evaluability. The review of toxicity and tolerability prompted investigators to reduce the rucaparib starting dose to 400 mg twice a day and ipilimumab was limited to 4 cycles for the last 4 individuals in the study.

The median age of the 15 individuals in the study was 64 years old. The adverse events of the treatment included anemia, diarrhea/colitis, dyspnea, fatigue, hypophosphatemia, hyponatremia, lymphopenia, myocarditis, and rash.

All individuals evaluated experienced fatigue, and 6 experienced diarrhea/colitis, dyspnea, and hypophosphatemia. Additionally, 5 individuals experienced rash, 4 experienced lymphopenia and anemia, 3 experienced hyponatremia, and 1 experienced myocarditis.

The researchers noted that there were no treatment emergent adverse events greater than grade 3 in anemia, hypophosphatemia, hyponatremia, lymphopenia, and myocarditis. There were no adverse events greater than grade 3 for myocarditis.

In total, 7 individuals were used for the safety assessment, 4 of which started on 600 mg of rucaparib twice a day and 3 of which were on 400 mg of rucaparib twice a day. The median rucaparib dose intensity of the 7 individuals was 82.5%. There was 1 dose limiting toxicity, which was a grade 3 nephritis on day 18. Additionally, 1 individual died of Escherichia coli sepsis related to colitis.

Rucaparib at the 400 mg dosage combined with nivolumab and ipilimumab for 4 cycles will continue onto a phase 2 trial. The individuals in the study will be randomized on a 1 to 1 to 2 to trial arms that include single agent rucaparib; rucaparib and ipilimumab; and rucaparib, ipilimumab, and nivolumab. The individuals recruited to rucaparib alone are eligible for second randomization to add ipilimumab or ipilimumab and nivolumab at progression.

Reference

Hall M. CeNtuRIOn: Rucaparib (R) with nivolumab (N) and ipilimumab (I) in patients (pts) with relapsed ovarian cancer (ROC)—Results of an initial safety cohort. American Society of Clinical Oncology. June 01, 2022;5577-5577. doi:10.1200/JCO.2022.40.16_suppl.5577