Regulatory Decision Summary for Zynyz

The purpose of this new drug submission was to seek market authorization for Zynyz (retifanlimab) for the treatment of metastatic or recurrent locally advanced Merkel cell carcinoma.

After evaluation of the submitted data package, Health Canada authorized Zynyz for the following indication:

Zynyz (retifanlimab for injection), as monotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma not amenable to curative surgery or radiation therapy.

Authorization was based on results from an open-label, single-arm, multiregional study. In this study, patients (n = 101) with treatment-naïve metastatic or recurrent locally advanced Merkel cell carcinoma were treated with retifanlimab monotherapy 500 mg every 4 weeks until disease progression, unacceptable toxicity or up to 24 months.

The primary efficacy endpoint was confirmed objective response rate as assessed by an independent central review committee according to the Response Evaluation Criteria in Solid Tumor v1.1. Duration of response was a key secondary outcome. The objective response rate was 53.5% (95% confidence interval [CI]: 43.3%, 63.5%), with median Duration of response of 25.3 months (95% CI: 14.2, not reached).

The most common adverse reactions (ADRs) reported in at least 10% of patients who were treated with retifanlimab were pruritus, rash, fatigue, diarrhea, arthralgia, nausea, pyrexia and constipation. The safety finding of Zynyz was consistent with the safety profiles of therapeutic agents in the same class (i.e., PD-(L)1 inhibitors). The risks associated with the use of retifanlimab are adequately captured in the Product Monograph (PM).

Given the rarity of Merkel cell carcinoma, the clinically meaningful objective response rate and Duration of response, and the manageable safety profile, the benefits of retifanlimab monotherapy for the target patient population is considered outweigh the risks.

The recommended dose of retifanlimab monotherapy is 500 mg every 4 weeks administered as an intravenous infusion over 30 minutes. View the Product Monograph for details.

An updated Risk Management Plan (RMP) for Zynyz was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Zynyz has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

For further details about Zynyz, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.