On March 22, 2023, the FDA accelerated the approval of retifanlimab-dlwr (Zynyz; Incyte Corporation), a humanized monoclonal antibody targeting PD-1, for adult patients with metastatic or recurrent locally advanced Merkel-cell carcinoma (MCC). The FDA granted this indication priority review, fast track, and orphan drug designations. MCC is a rare and aggressive type of skin cancer that can manifest as a painless, discolored or flesh-colored skin nodule, usually in areas exposed to sunlight. This cancer has a high risk of recurrence.
This approval was based on the results of the phase 2 POD1UM-201 (NCT03599713) study, an open-label, multiregional, single-arm, clinical trial including 65 patients with metastatic or recurrent locally advanced MCC who had not received systemic therapy for advanced disease.
The main efficacy measures were objective response rate (ORR) and duration of response (DOR). The ORR was 52% (95% confidence interval, 40-65); the complete response rate was 18%, and 34% achieved partial response. Among the responding patients, a DOR ≥6 months occurred in 26 (76%) patients, and a DOR ≥12 months was seen in 21 (62%) patients.
A total of 105 patients with MCC comprised the safety population. The most common (≥10%) adverse events were fatigue, musculoskeletal pain, pruritus, diarrhea, rash, pyrexia, and nausea; 22% of patients receiving retifanlimab had serious adverse events.
“More than a third of patients with MCC present with regional or distant metastases, which are associated with high rates of mortality,” said Shailender Bhatia, MD, University of Washington and Fred Hutchinson Cancer Center, Seattle, WA. “The approval of Zynyz offers healthcare providers another first-line treatment option against MCC that can result in durable responses in patients with metastatic disease.”
The recommended dosage of retifanlimab-dlwr is 500 mg administered as an intravenous infusion for 30 minutes every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months.
The continued approval of retifanlimab for this indication may be contingent on additional confirmatory trials that verify and describe the clinical benefit.