Final results of POD1UM-201, a phase 2 study of retifanlimab, a humanized anti–PD-1 antibody, in patients with advanced or metastatic Merkel cell carcinoma (MCC).

9536 Background: Retifanlimab is approved in the United States and Europe for treatment of adults with metastatic or recurrent locally advanced MCC, based on previously reported results from the open-label single-arm POD1UM-201 study (NCT03599713). As previously reported, objective response rate (ORR) was 54% (95% confidence interval [CI], 43, 64) and probability of remaining progression free at 12 months was 71% (Grignani G, et al. Ann Oncol. 2023;34(suppl 2):S686). Safety profile was as expected for the PD-(L)1 inhibitor class. Here, we present the final results from POD1UM-201 based on extended follow-up. Methods: Eligible patients were aged ≥18 years with metastatic or recurrent unresectable locoregional MCC, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Prior systemic treatment for MCC was not allowed. Retifanlimab 500 mg was administered intravenously once every 4 weeks for up to 2 years. Premedication prophylaxis was not routinely administered. The primary endpoint was ORR assessed by independent central review per RECIST v1.1. Key secondary endpoints were duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety. Results: The study enrolled 101 patients in North America and Europe between February 12, 2019, and June 16, 2021. Patients had a median age of 71 (range: 38, 90) years, 68 (67%) were male, 77% were White, 74 (73%) had an ECOG PS of 0, and 1 (1%) patient was HIV positive. 91 patients (90%) had stage IV disease, 69 (68%) had prior surgery, and 37 (37%) had prior radiotherapy. Merkel cell polyomavirus and PD-L1 expression were detectable in 73 (72%) and 83 (82%) patient tumor samples, respectively. Median follow-up duration was 36 (range: 1, 60) months. Summary efficacy results are shown in the Table. ORR was 55% (95% CI, 44, 64), with complete response observed in 18 patients (18%). Median DOR was not reached and probability of remaining progression free at 36 months was 57%. Most common immune-related adverse events (irAEs) were skin reactions (10%), including pruritus (4%) and rash (3%), and hypothyroidism (8%); 11% of patients had grade ≥3 irAEs and 9% discontinued treatment due to irAEs. Conclusions: Retifanlimab is a highly active treatment for advanced MCC with a safety profile that is representative of the PD-(L)1 inhibitor class. Clinical trial information: NCT03599713 . Summary of efficacy. Study Endpoint N=101 Overall response rate (95% CI), % 55 (44, 64) Complete response, n (%) 18 (18) Partial response, n (%) 37 (37) Disease control rate (95% CI), % 60 (50, 70) Duration of response, median (range), months NR (23, NE) Progression-free survival, median (range), months 16 (9, 32) Overall survival, median (range), months NR (45, NE) CI, confidence interval; NE, not estimable; NR, not reached.