SWOG/NCI Phase II Dual Anti-CTLA-4/PD-1 Blockade in Rare Tumors: Nonepithelial Ovarian Cancer

Area of Science:

• Oncology
• Immunotherapy
• Gynecologic Cancers

Background:

• Advanced rare/ultrarare nonepithelial ovarian cancers often lack effective standard therapies.
• Dual checkpoint inhibition, combining ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1), is an emerging treatment strategy.

Purpose of the Study:

• To explore the efficacy and safety of dual checkpoint inhibition in advanced nonepithelial ovarian cancers.
• To assess overall response rate (ORR), progression-free survival (PFS), and overall survival in this patient population.

Main Methods:

• A prospective, multicenter, single-arm, phase II trial involving 17 adult patients with advanced nonepithelial ovarian cancers.
• Patients received ipilimumab (1 mg/kg IV every 6 weeks) and nivolumab (240 mg IV every 2 weeks).
• Outcomes included ORR (complete response/partial response), PFS, overall survival, clinical benefit rate, and toxicity.

Main Results:

• The overall response rate (ORR) was 25% (2/8) in granulosa cell tumors, with one complete response and one partial response lasting over 4 years.
• Median PFS was 3.5 months, and median overall survival was 42.5 months.
• Carcinosarcomas showed no response; one Sertoli-Leydig cell tumor had 22% regression. 18% of patients discontinued due to adverse events.

Conclusions:

• Dual ipilimumab-nivolumab therapy shows promising activity in treatment-refractory granulosa cell tumors.
• This immunotherapy approach warrants further investigation for rare nonepithelial ovarian cancers.