FDA Approves Zynyz (retifanlimab-dlwr) for Metastatic Anal Canal Cancer and Merkel Cell Carcinoma

Zynyz is a programmed death receptor-1 (PD-1)–blocking antibody.

Zynyz is indicated for three specific patient populations: 1) Adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) for first-line treatment in combination with carboplatin and paclitaxel. 2) Adult patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy, as a single agent. 3) Adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).

The recommended dosage of Zynyz is 500 mg administered as an intravenous infusion over 30 minutes every 4 weeks. For SCAC in combination with carboplatin and paclitaxel, treatment continues until disease progression, unacceptable toxicity, or up to 12 months. For monotherapy in SCAC (post-platinum) and for MCC, treatment continues until disease progression, unacceptable toxicity, or up to 24 months. No dose reduction is recommended. The label provides specific instructions for withholding or permanently discontinuing therapy based on the type and severity of adverse reactions.

Trial data not available in label.

The label contains warnings and precautions for immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, exfoliative dermatologic conditions, myocarditis, and neurological toxicities. It also warns of infusion-related reactions. Recommended dosage modifications for these adverse reactions are provided in a detailed table, specifying when to withhold or permanently discontinue therapy based on severity grade. The label states to permanently discontinue Zynyz for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions requiring systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.

For squamous cell carcinoma of the anal canal (SCAC), Zynyz is approved for first-line use in combination with carboplatin and paclitaxel for inoperable locally recurrent or metastatic disease. It is also approved as a single agent for patients with locally recurrent or metastatic SCAC who have disease progression on or are intolerant to platinum-based chemotherapy. For Merkel cell carcinoma (MCC), Zynyz is approved as a single agent for the treatment of metastatic or recurrent locally advanced disease.