Interim analysis demonstrated a 6.2-month improvement in median overall survival, with follow-up ongoing. 

The U.S. Food and Drug Administration (FDA) has approved retifanlimab-dlwr (Zynyz), a PD-1–targeted humanized monoclonal antibody, for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) in combination with carboplatin and paclitaxel. The FDA also granted approval to retifanlimab as monotherapy in patients with SCAC who have experienced disease progression on or are intolerant to platinum-based chemotherapy.

Approval was based on results from the phase 3 POD1UM-303/InterAACT2 and phase 2 POD1UM-202 trials.

In the POD1UM-303/InterAACT2 trial, patients in the retifanlimab and chemotherapy combination group experienced a 37% reduction in the risk of disease progression or death compared to those in the placebo combination group. Median progression-free survival was 9.3 months with the addition of retifanlimab versus 7.4 months with placebo. Interim analysis demonstrated a 6.2-month improvement in median overall survival, with follow-up ongoing. Serious adverse events occurred in 47% of patients receiving the combination therapy, most commonly sepsis and pulmonary embolism (each 3.2%).

The POD1UM-202 trial evaluated retifanlimab monotherapy in patients with previously treated, advanced SCAC. The objective response rate was 14%, and the disease control rate was 49%. Serious adverse events were reported in 40% of patients, including infections, abdominal pain, anemia, and urinary tract infections.

Retifanlima demonstrated a safety profile consistent with PD-1 inhibition, with no compromise in human immunodeficiency virus infection control among affected patients.

Retifanlimabcarries a warning for immune-mediated adverse effects, which may involve multiple organ systems and can be severe or fatal. Clinicians are advised to monitor patients throughout treatment and post-therapy for signs of immune-related toxicity. Management may require corticosteroids, hormone replacement, or treatment discontinuation, depending on severity.

SCAC remains a rare malignancy with rising incidence and historically limited systemic treatment options. Additional regulatory submissions for retifanlimab are under review in the European Union and Japan.

Source: Incyte