Phase 2 study of pembrolizumab plus lenvatinib as second-line treatment for pleural mesothelioma

Cohort 2 of the phase 2 PEMMELA study at the Netherlands Cancer Institute (Amsterdam) evaluated the second-line combination of pembrolizumab (anti-PD-1) and lenvatinib (multi-TKI) in patients with pleural mesothelioma after progression on first-line nivolumab plus ipilimumab. Patients were aged 18 years or older and had an ECOG performance status 0 or 1. Patients received intravenous pembrolizumab 200 mg every 3 weeks plus oral lenvatinib 20 mg once daily for up to 2 years, or until progression or unacceptable toxicity. The primary endpoint was objective response rate. At data cutoff, with a median follow-up of 11.9 months (IQR 10.8-15.8), 12 of 20 patients had an objective response (60%; 95% CI 36-81). Grade 3 or 4 treatment-related adverse events were seen in 14 patients (70%). Nine patients (45%) required at least one dose reduction and two (10%) discontinued treatment due to toxicity. There were no treatment-related deaths. The authors conclude that the study met its primary endpoint, showing high clinical activity of pembrolizumab plus lenvatinib, be it with substantial toxicity, in patients with pleural mesothelioma who had progressed after first-line nivolumab plus ipilimumab.