Multicenter phase 2 trial of risovalisib for PIK3CA-mutated recurrent of persistent ovarian clear cell carcinoma

Ovarian clear cell carcinoma (OCCC) is an aggressive and biologically distinct subtype of ovarian cancer, in which PIK3CA mutations are common. Advanced OCCC is difficult to treat, and after failure of platinum-based chemotherapy, therapeutic options are limited. A phase 2 trial at 27 centers in China and 12 centers in Japan evaluated the PI3Kα inhibitor risovalisib for recurrent or persistent PIK3CA-mutated OCCC. Eligible participants were adults with an ECOG performance status 0 or 1 with one to three previous systemic antitumor treatment. Risovalisib was given orally at 40 mg daily until disease progression, unacceptable toxicity, or other protocol-defined reasons for discontinuation. The primary endpoint was objective response rate (ORR) assessed by blinded independent review committee. A total of 93 patient were enrolled and received risovalisib. The median duration of follow-up was 14.5 months (IQR 8.6-18.3). The ORR was 35% (95% CI 25-46). The most commonly reported grade 3 or worse treatment-related adverse events were rash (32% of patients), hyperglycemia (30%), and weight loss (78%). Treatment-related serious adverse events occurred in 39%. There were no treatment-related deaths. The authors conclude that these results support risovalisib as a potential novel treatment option for PIK3CA-mutated OCCC.