Retifanlimab Extends Progression-Free Survival in SCAC Patients; Data at ESMO 2024

Incyte has revealed the results of its Phase 3 POD1UM-303/InterAACT2 trial involving retifanlimab (Zynyz®), a humanized monoclonal antibody aimed at programmed death receptor-1 (PD-1), combined with platinum-based chemotherapy (carboplatin-paclitaxel) for adults with inoperable locally recurrent or metastatic squamous cell anal carcinoma (SCAC). These findings were presented during a Presidential Symposium at the 2024 European Society for Medical Oncology (ESMO) Congress in Barcelona, both in-person and virtually.

The POD1UM-303/InterAACT2 trial, which builds upon previously announced topline results, has successfully achieved its primary endpoint. It demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for patients with SCAC who had not previously undergone systemic therapy. The addition of retifanlimab to standard chemotherapy reduced the risk of progression or death by 37%, with a median PFS of 9.3 months for the treatment group versus 7.4 months for the placebo group.

Dr. Pablo J. Cagnoni, President and Head of Research and Development at Incyte, highlighted the trial's significance, noting it as the first and largest Phase 3 study evaluating a checkpoint inhibitor for SCAC, a condition with substantial medical need. Dr. Cagnoni emphasized the potential of retifanlimab, in conjunction with carboplatin and paclitaxel, to establish a new standard of care for advanced SCAC. He also mentioned plans to engage with regulatory authorities to advance the supplemental Biologics License Application (sBLA) for retifanlimab.

Secondary endpoints of the trial also showed promising improvements. An interim analysis for overall survival (OS) revealed that patients receiving the combination treatment experienced a median OS of 29.2 months, compared to 23 months for the placebo group, showing a strong trend towards statistical significance. Additionally, the overall response rate (ORR) and duration of response (DOR) improved in the retifanlimab group compared to the placebo group, with ORR at 56% versus 44% and DOR at 14 months versus 7 months.

Retifanlimab was generally well-tolerated, with safety outcomes consistent with other chemotherapy plus checkpoint inhibitor regimens. The most common treatment-emergent adverse events (TEAEs) in the retifanlimab combination group were anemia, nausea, and alopecia.

Dr. Sheela Rao, a Consultant Medical Oncologist at The Royal Marsden National Health Service Foundation Trust, commented on the trial's significance, noting the long-standing need for new treatment options for advanced SCAC. Dr. Rao expressed optimism that the trial results could pave the way for a new treatment option, combining retifanlimab with platinum-based chemotherapy for patients with inoperable locally recurrent or metastatic SCAC.

Squamous cell anal carcinoma (SCAC) is an orphan disease with a rising incidence rate of approximately 3% per year, primarily due to human papillomavirus (HPV). Additionally, individuals with human immunodeficiency virus (HIV) are significantly more likely to develop SCAC. Patients with unresectable metastatic SCAC typically have poor 5-year survival rates, and currently, no FDA-approved treatments exist for advanced stages of the disease.

The POD1UM clinical trial program for retifanlimab includes several Phase 1, 2, and 3 studies across various solid tumors. The POD1UM-303/InterAACT2 trial is a randomized, multicenter, double-blind, placebo-controlled study evaluating the efficacy of retifanlimab combined with platinum-based chemotherapy in adult patients with inoperable locally recurrent or metastatic SCAC who have not received prior systemic chemotherapy.

Overall, the results from the POD1UM-303/InterAACT2 trial offer promising evidence for the potential role of retifanlimab in combination with chemotherapy to provide a new standard-of-care treatment for patients with advanced SCAC.