Neoadjuvant lenvatinib plus pembrolizumab in Merkel cell carcinoma: an investigator-initiated, open-label phase II trial
February 20, 2026
Journal
Journal for ImmunoTherapy of Cancer
Publication Date
February 20, 2026
Authors
Merkelcell.org Summary
About 3 in 10 patients diagnosed with Merkel cell carcinoma (MCC) will develop cancer that spreads beyond where the tumor originally started (advanced MCC). When advanced MCC is found, doctors often use immunotherapy, which is a drug that boosts the immune system to better fight cancer. Sometimes, doctors will give immunotherapy before a patient receives radiation therapy or surgery to help shrink the tumor and strengthen the immune system. This is called neoadjuvant immunotherapy.
This study looked at using pembrolizumab, a common type of immunotherapy used to treat MCC, in combination with Lenvatinib, a medication that blocks several proteins involved in tumor growth and blood vessel formation. Lenvatinib has not been used to treat MCC before but is often used with immunotherapy drugs like pembrolizumab to treat other types of cancer. From 2021-2024, 26 MCC patients were given neoadjuvant Lenvatinib daily for 6 weeks and pembrolizumab every three weeks for a year. After their second dose of neoadjuvant pembrolizumab, they received surgery and/or radiation, then continued to receive only pembrolizumab for one year.
About 60% of the patients had all their MCC go away after one year of this treatment. About 10% had some of their MCC go away and 20% did not have a change in their MCC. The most common severe side effect of this treatment was hypertension (high blood pressure), experienced by a little over half of the patients. Other common side effects were fatigue, diarrhea, and headaches. Two years after starting the treatment, about 65% of the patients did not have their MCC come back, and only one patient had passed away from MCC.
This study shows that combining Lenvatinib with pembrolizumab before surgery or radiation may be an effective treatment option for MCC that has spread. However, the study did not compare the combination treatment directly with pembrolizumab or Lenvatinib alone to determine whether the combination works better. Larger studies are needed to confirm these findings.
Abstract
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.