Long-term outcomes after discontinuation of retifanlimab in patients with advanced or metastatic Merkel cell carcinoma (MCC) in the POD1UM-201 trial.

9538 Background: Retifanlimab is a humanized programmed cell death protein-1 (PD-1)–blocking antibody that is approved for treatment of adults with metastatic or recurrent locally advanced MCC in the United States and Europe. Approval was based on primary results from the phase 2, open-label, single-arm POD1UM-201 study (NCT03599713). Here, we present long-term outcomes in patients with MCC who discontinued retifanlimab for reasons other than confirmed disease progression, as previous studies have suggested high rates of recurrence in patients discontinuing treatment after initial response. Methods: POD1UM-201 enrolled patients with metastatic or recurrent unresectable locoregional MCC who had not received prior systemic treatment. Retifanlimab was administered every 4 weeks (q4w) intravenously (IV) for a maximum of 2 years, or until progressive disease (PD) or unacceptable toxicity. Patients with complete response (CR) were permitted to discontinue treatment after a minimum of 6 months at investigator discretion. Patients who discontinued retifanlimab for reasons other than PD were closely followed for disease status by independent central review (ICR) until disease progression or death. Results: The study enrolled 101 patients with a median (range) follow-up duration of 36 (1, 60) months. Objective response rate was 55% and disease control rate was 60%, including 18 patients (18%) with CR, 37 (37%) with partial response (PR), and 6 (6%) with stable disease (SD) for ≥6 months. Sixty-four patients (63%) discontinued treatment prior to completion of therapy, most commonly due to tumor progression. Forty-one patients were continuing to demonstrate ICR confirmed benefit when treatment was discontinued (CR, n=15; PR, n=21; SD, n=5). Of these patients, 26 (63%) completed the protocol-defined maximum 2 years of therapy, 3 (7%) discontinued at the discretion of the investigator after CR was achieved, and 12 (29%) discontinued due to toxicity. Among the patients with CR or PR, 30 (83%) were alive without disease progression at time of last follow-up after a median (range) of 18 (2, 46) months. Patients who achieved a CR or PR had a lower rate of PD or death compared with those with SD; 7% of patients with a CR experienced PD during follow-up vs 24% of patients with a PR and 60% of patients with SD. Conclusions: Retifanlimab 500 mg administered q4w IV for up to 2 years led to durable clinical responses in the majority of patients with advanced MCC. Most patients with an ongoing objective response (CR or PR) remain progression free beyond discontinuation of therapy, suggesting sustained benefit is possible in patients with this highly aggressive disease. Clinical trial information: NCT03599713 .