Pembrolizumab + Lenvatinib (PD-1 + VEGFR/MET/FGFR TKI) Hits 30% ORR and 76% 6-mo PFS in Chemoresistant Clear-Cell Ovarian Cancer

Pembrolizumab, an anti-PD-1 antibody, was paired with the multi-kinase anti-angiogenic agent lenvatinib in a two-stage, single-arm phase 2 trial (NCT05296512). Thirty women with recurrent or persistent clear-cell ovarian carcinoma (median 3 prior lines; bevacizumab and prior checkpoint inhibitors allowed) received pembrolizumab 200 mg IV Q3W in combination with lenvatinib 20 mg PO daily. Confirmed objective responses were seen in 9/30 patients (30%; 2 CR, 7 PR) with another 3 unconfirmed PRs. The mPFS reached 10.9 months, and the 6-month PFS was 75.9% (95% CI 54–89). The twelve-month PFS was 48.9%. The most common side effects, of any grade, were hypertension (71%), hypothyroidism (66%), fatigue (60%). There were no unexpected safety signals. Two cases of grade 3 acute kidney injuries were the only serious immune-related events. Historical single-agent pembrolizumab in ovarian cancer reports an ORR ≈ 8% and median PFS ≈ 3 months, while multi-TKI therapy alone shows minimal activity—underscoring the additive effect of dual immune-angiogenic blockade in this chemoresistant histology.