Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201)

Merkelcell.org Summary

Immunotherapy is a treatment that strengthens the immune system so it can better recognize and destroy cancer cells. It is now a standard therapy for Merkel cell carcinoma (MCC), especially in cases where surgery or radiation alone cannot fully control the disease. Prior to the POD1UM-201 trial, pembrolizumab (Keytruda) and avelumab (Bavencio) were the only two immunotherapy drugs FDA-approved to treat MCC in the U.S. The POD1UM-201 trial evaluated another immunotherapy drug, called retifanlimab, to see if it also works to treat MCC. A unique aspect of retifanlimab is that it is given once every four weeks, less frequently than several other options.

A total of 101 MCC patients participated in the POD1UM-201 trial across 34 different hospital sites in the US, Canada, and Europe. To qualify for the trial, patients’ cancer had spread beyond the original location, their tumors could not be removed with surgery or treated with radiation, and they had not received chemotherapy or immunotherapy before. Each patient got retifanlimab once a month for up to two years.

Patients were followed for an average of two months after starting treatment. 18 patients (18%) had a complete response to the treatment, meaning their cancer completely disappeared, and 37 patients (37%) had a partial response. In total, 60% of patients had their disease controlled after treatment, meaning the MCC did not come back or spread. On average, patients stayed cancer-free for about 16 months, and 63% were still alive three years after starting treatment. Serious side effects happened in 11% of patients.

Overall, the trial showed that retifanlimab can give long-lasting benefits in treating MCC, with manageable side effects, similar to prior approved medications, including Keytruda and Bavencio. These results helped the FDA approve retifanlimab as a new treatment for MCC.

Abstract

Background: POD1UM-201, an open-label, single-arm, phase II multiregional study, evaluated efficacy and tolerability of retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in chemotherapy-naive patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).

Methods: Patients were enrolled across 34 sites in the USA, Canada, and Europe. Eligible patients were ≥18 years with confirmed recurrent advanced locoregional or metastatic MCC not amenable to surgery or radiation therapy, had not received previous systemic treatment, had measurable disease, and Eastern Cooperative Oncology Group performance status 0-1. Retifanlimab 500 mg was administered intravenously every 4 weeks (Q4W) for up to 2 years. The primary endpoint was objective response rate (ORR). Key secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

Results: A total of 101 patients were enrolled between February 12, 2019, and June 16, 2021, with a median duration of follow-up for response of 22.2 (range: 1.1-55.3) months. ORR was 54.5% (95% CI: 44.2% to 64.4%; n=55), including 18 patients (17.8%) with complete responses (CRs) and 37 (36.6%) with partial responses (PRs). DCR was 60.4% (95% CI: 50.2% to 70.0%; n=61). Median DOR was not reached (95% CI: 14.0 months to not estimable (NE)) in patients who achieved CR and was 25.3 months (95% CI: 14.2 months to NE) in those with PR. With a median follow-up of 9.3 (range: 0.0-57.1) months, the estimated median PFS was 16.0 months (95% CI: 9.0 months to 32.2). Median OS was not reached with 63% of patients alive at 3 years. The safety profile was representative of the PD-(ligand)1 inhibitor class, with grade 3 immune-related adverse events occurring in 11 patients (10.9%).

Conclusions: Retifanlimab 500 mg Q4W led to frequent and durable responses in chemotherapy-naive patients with advanced MCC with an acceptable safety profile. Retifanlimab represents a new immunotherapy option for patients with locally advanced or metastatic MCC.

Trial registration number: NCT03599713; EudraCT 2018-001627-39.

Keywords: Immune Checkpoint Inhibitor; Monoclonal antibody; Skin Cancer.