ASCO Conference Coverage

Pembrolizumab and Lenvatinib Show 30% Response Rate in Clear Cell Ovarian Carcinoma

Miranda Manier, BA

Key Highlights

  • 30% of patients with recurrent or persistent clear cell ovarian carcinoma had confirmed responses to pembrolizumab plus lenvatinib therapy.
  • The estimated 6-month progression-free survival (PFS) was 75.96%, with a median PFS of 10.9 months.
  • No unanticipated treatment-related adverse events were reported.
  • Both co-primary endpoints were met, indicating the combination warrants further study.

The combination of pembrolizumab and lenvatinib in patients with recurrent or persistent clear cell ovarian carcinoma (COCC) demonstrated encouraging clinical activity, according to the authors of a study presented at the 2025 American Society of Clinical Oncology Annual Meeting. The trial met both co-primary endpoints and observed notable response rates and progression-free survival in this rare and chemoresistant subtype of ovarian cancer.

COCC is a chemoresistant subtype of ovarian cancer with limited effective treatment options. Immune checkpoint inhibitors have demonstrated activity in this subtype, and the molecular features of CCOC suggest a role for anti-angiogenic agents. This study was conducted to evaluate the clinical activity of combining a PD-1 inhibitor (pembrolizumab) with an anti-angiogenic tyrosine kinase inhibitor (lenvatinib) in this difficult-to-treat population.

The phase II single-arm, two-stage trial enrolled patients with measurable disease. Participants received pembrolizumab 200 mg intravenously every 3 weeks and lenvatinib 20 mg daily. Eligible patients could have had an unlimited number of prior therapies, including prior bevacizumab or immune checkpoint inhibitors, but prior lenvatinib was an exclusion criterion. Patients with malignant bowel involvement were also excluded. The co-primary endpoints were objective response rate and the rate of progression-free survival (PFS) at 6 months, with statistical hypotheses designed to control for type I and II errors at 10% each. At the data cutoff of October 22, 2024, 83.3% of patients were White, and the mean age was 54.1 years.

Of the 30 enrolled patients, nine (30%) experienced confirmed responses, including two complete responses (CR) and seven partial responses (PR). An additional three patients had unconfirmed PRs, and four patients had stable disease lasting at least 6 months. At a median follow-up of 9.72 months, 16 patients were alive and progression-free at 6 months, with an estimated 6-month PFS of 75.96% (95% CI, 53.82-88.51%) and a median PFS of 10.9 months. The estimated 12-month PFS was 48.86% (95% CI, 23.67-70.04%). The most common any-grade treatment-related adverse events (TRAE) were hypertension (71%), hypothyroidism (66%), and fatigue (60%), with no unanticipated TRAEs observed.

“The combination of pembrolizumab/lenvatinib demonstrates encouraging evidence of clinical activity in CCOC, with nine [patients] experiencing a confirmed response and 16 [patients] alive and progression-free at 6 months,” the study authors concluded.

Reference:

Lee EK, Zhou Y, Wahner Hendrickson AE, et al. A phase II trial of pembrolizumab and lenvatinib in recurrent or persistent clear cell ovarian carcinoma (NCT05296512). Presented at: 2025 American Society of Clinical Oncology (ASCO) Annual Meeting; 2025 May 30–June 3; Chicago, IL. https://www.asco.org/annual-meeting