The US Food and Drug Administration (FDA) has granted approval for Incyte’s Zynyz (retifanlimab-dlwr), a humanised monoclonal antibody targeting PD-1, to be used alongside carboplatin and paclitaxel for the initial treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC).
The approval also extends to the use of Zynyz as a standalone treatment for adults with locally recurrent or metastatic SCAC who have either progressed on or cannot tolerate platinum-based chemotherapy.
The FDA’s decision followed a Priority Review of the supplemental Biologics License Application (sBLA) for Zynyz, informed by two key clinical trials, said the company.
The Phase 3 POD1UM-303/InterAACT2 trial assessed Zynyz in combination with platinum-based chemotherapy in adult patients with metastatic or inoperable locally recurrent SCAC not previously treated with systemic chemotherapy.
Meanwhile, the Phase 2 POD1UM-202 trial evaluated Zynyz monotherapy in patients with locally advanced or metastatic SCAC who had either progressed on or were intolerant of platinum-based chemotherapy.
Results from the POD1UM-303/InterAACT2 trial, presented at the European Society for Medical Oncology (ESMO) 2024, indicated a 37% reduction in the risk of progression or death for patients receiving the Zynyz and chemotherapy combination, compared to those on a placebo combination.
The median progression-free survival was 9.3 months for the Zynyz group, compared to 7.4 months for the placebo group. An interim analysis showed a 6.2-month improvement in median overall survival, though follow-up continues. No new safety concerns were identified, although serious adverse reactions were noted in 47% of patients receiving the combination therapy.
The approval of Zynyz as a monotherapy was based on the POD1UM-202 study, which reported an objective response rate of 14% and a disease control rate of 49%. The safety profile of Zynyz was consistent with expectations for a PD-1 inhibitor, with serious adverse reactions occurring in 40% of patients. Common serious adverse reactions included infections, pain, anaemia, haemorrhage, and respiratory issues.
Incyte has also pursued regulatory approvals beyond the US. A Type II variation Marketing Authorisation Application (MAA) has been submitted to the European Medicines Agency (EMA) for retifanlimab in advanced SCAC. Additionally, a Japanese New Drug Application (J-NDA) has been accepted by the Pharmaceuticals and Medical Devices Agency (PMDA) for the same indication.
Incyte CEO Hervé Hoppenot said: “The FDA approval of Zynyz marks a pivotal moment, bringing effective combination and monotherapy treatment options to patients with advanced anal cancer after decades of limited innovation.
“At Incyte, we focus our efforts where we can make the biggest impact for patients. I am proud of our scientists and development teams for their perseverance in delivering the first approved PD-1 inhibitor to US patients with SCAC.”
