Neoadjuvant lenvatinib plus pembrolizumab in Merkel cell carcinoma: an investigator-initiated, open-label phase II trial

Background Given the success of checkpoint inhibitor therapy in the advanced Merkel cell carcinoma (MCC) setting, there is interest in exploring immunotherapy as a neoadjuvant approach. We report the primary results of a neoadjuvant study of lenvatinib plus pembrolizumab in resectable MCC. Methods In this single-center, phase II open-label trial, resectable stage II–IV MCC patients received 6 weeks of neoadjuvant therapy with lenvatinib 20 mg orally daily plus pembrolizumab 200 mg intravenous dose every 3 weeks. Following local therapy, patients received continued adjuvant pembrolizumab monotherapy to complete a total treatment duration of 1 year. Pathological complete response (pCR) rate was the primary endpoint of the study. Results 26 patients were enrolled, including 5 (19.2%) with clinical stage II disease, 20 (76.9%) with stage III, and 1 (3.8%) with stage IV. Following neoadjuvant treatment, 2 patients (7.7%) were unable to undergo planned surgery, one due to progressive disease and one due to toxicity. On intention to treat, 15 of the 26 patients (57.7%) achieved pCR. Among 22 radiographically evaluable patients, 16 (72.7%) achieved an objective response. At a median follow-up of 20.0 months, median progression-free survival (PFS) has not been reached. PFS significantly correlated with radiographic response to neoadjuvant therapy. pCR was associated with superior PFS, though this result was not statistically significant (p=0.22). Grade 3 treatment-related adverse events (TRAEs) occurred in 14 patients (53.8%), most commonly grade 3 hypertension in 11 patients (42.3%). No grade 4–5 TRAEs were observed. Conclusions Lenvatinib plus pembrolizumab demonstrated encouraging efficacy with anticipated toxicity when used as neoadjuvant therapy for MCC. Further investigation of these promising findings is warranted. Trial registration number NCT04869137 .