Multicenter phase 2 trial of pembrolizumab plus lenvatinib for recurrent gynecological clear cell carcinoma

Combined targeting of angiogenic and immune pathways is an emerging strategy in clear cell carcinomas arising from the gynecological tract (CCGCs). The phase 2 LARA trial, at three tertiary hospitals in Singapore and South Korea, evaluated the combination of pembrolizumab and lenvatinib for recurrent CCGC. The trial included 27 adult patients with CCGC which had progressed after at least one line of platinum-based chemotherapy, an ECOG performance status 0 or 1, and no previous exposure to immune checkpoint inhibitor therapy. Patients received 200 mg intravenous pembrolizumab every 3 weeks plus 20 mg oral lenvatinib daily, until disease progression or unacceptable toxicity, or for 2 years. Primary endpoint was investigator-assessed objective response rate in the first 24 weeks of treatment. At a median follow-up of 21.0 months (IQR 12.5-25.2), 10 of 25 evaluable patients had confirmed objective response (ORR at 24 weeks 40%; 95% CI 21-61). Grade 3 or 4 treatment-related adverse events occurred in 14 (52%) of 27 patients, and serious adverse events occurred in 5 (19%) patients. No treatment-related deaths occurred. The authors conclude that pembrolizumab plus lenvatinib showed promising antitumor activity and manageable safety in patients with recurrent CCGC.