Report on Retifanlimab (Zynyz): A Comprehensive Clinical and Pharmacological Monograph

Section 1: Executive Summary

Retifanlimab, marketed under the brand name Zynyz, is a humanized IgG4 kappa monoclonal antibody that functions as a programmed death receptor-1 (PD-1) blocking antibody. It represents a significant addition to the therapeutic armamentarium for specific, difficult-to-treat malignancies. The drug has secured regulatory approval in major markets for two primary indications: metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) and squamous cell carcinoma of the anal canal (SCAC). Its most notable achievement is its approval by the U.S. Food and Drug Administration (FDA) as the first and only PD-1 inhibitor-based regimen for the first-line treatment of adult patients with inoperable locally recurrent or metastatic SCAC, establishing a new standard of care in this setting.

The clinical development program for Retifanlimab is anchored by three pivotal trials. The PODIUM-201 study, a Phase 2 trial in chemotherapy-naive MCC patients, demonstrated robust and durable antitumor activity, leading to its accelerated approval. The final analysis of 101 patients showed an objective response rate (ORR) of 54.5%, with a median duration of response (DOR) that was not reached after a median follow-up of 36 months. For SCAC, the Phase 3 POD1UM-303/InterAACT 2 trial was a landmark study. It showed that the addition of Retifanlimab to standard carboplatin-paclitaxel chemotherapy resulted in a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy plus placebo (median PFS 9.3 vs. 7.4 months; Hazard Ratio 0.63; p=0.0006). Furthermore, the Phase 2 POD1UM-202 trial established the efficacy of Retifanlimab monotherapy in patients with SCAC who had progressed on or after platinum-based chemotherapy, showing an ORR of 13.8% with durable responses.