General Information

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

Zynz is specifically indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).

Zynz is supplied as a solution for intravenous administration. The recommended dosage of Zynz is 500 mg administered as an intravenous infusion over 30 minutes every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months.  

Mechanism of Action

Zynyz (retifanlimab-dlwr) is a programmed death receptor-1 (PD-1)–blocking antibody. Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Retifanlimab-dlwr binds to the PD-1 receptor, blocks interaction with its ligands PD-L1 and PD-L2, and potentiates T-cell activity.

Side Effects

Adverse effects associated with the use of Zynz may include, but are not limited to, the following:

• fatigue
• musculoskeletal pain
• pruritus
• diarrhea
• rash
• pyrexia
• nausea

Serious adverse reactions occurred in 22% of patients receiving Zynyz. The most frequent serious adverse reactions were fatigue, arrhythmia and pneumonitis.

Clinical Trial Results

Zynz for MCC was approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

The FDA accelerated approval was based on data from the POD1UM-201 trial, an open-label, multiregional, single-arm study that evaluated Zynyz in adults with metastatic or recurrent locally advanced MCC who had not received prior systemic therapy for their advanced disease. Among chemotherapy-naïve patients (n=65), Zynyz monotherapy resulted in an objective response rate (ORR) of 52% as determined by independent central review (ICR) using RECIST v1.1. Complete response was seen in 12 patients (18%), and 22 patients (34%) showed partial response. Among the responding patients, the duration of response (DOR) ranged from 1.1 to 24.9+ months, and 76% (26/34) experienced a DOR of six months or longer, and 62% (21/34) experienced a DOR of 12 months or longer by landmark analysis.