Incyte's PD-1 inhibitor, Zynyz (retifanlimab), is showing renewed promise in treating squamous cell carcinoma of the anal canal (SCAC). New data from the POD1UM-303 study, presented at ESMO, indicates that Zynyz, when combined with chemotherapy, could become a new first-line treatment option for this rare cancer. This development follows a previous FDA rejection for Zynyz as a second-line treatment for SCAC.
The POD1UM-303 study revealed that the Zynyz regimen reduced the risk of disease progression or death by 37% compared to chemotherapy alone (p<0.05). The median progression-free survival (PFS) was extended to 9.3 months from 7.4 months. While the overall survival (OS) data is not yet mature, there was a notable trend towards improvement, with a 30% increase in OS observed in patients taking Zynyz compared to the control group (29.2 months vs. 23 months).
Clinical Impact and Significance
The results of the POD1UM-303 trial mark the first time a checkpoint inhibitor has demonstrated activity in frontline SCAC in a phase 3 trial. Experts suggest that Zynyz plus chemotherapy could become the new standard of care for SCAC. SCAC, often linked to human papillomavirus (HPV) infection, affects approximately 10,000 individuals annually in Europe and the US, with increasing incidence among women in recent years.
Current Treatment Landscape and Unmet Needs
Treatment options for SCAC have been limited, primarily consisting of chemotherapy and radiotherapy. The potential approval of Zynyz could provide a much-needed new therapeutic avenue for patients. Incyte believes that the PFS data alone may be sufficient to support regulatory approval. While Zynyz is not projected to be a major revenue driver, Incyte anticipates it will play a crucial role in supporting the development of other drugs in their oncology pipeline.
Incyte's CDK2 Inhibitor
Incyte is also advancing its pipeline with potential first-in-class CDK2 inhibitor INCB123667. In a phase 1b study presented at ESMO, INCB123667 demonstrated activity against a range of solid tumors with biomarkers indicative of CDK2-driven mechanisms, including ovarian, endometrial, breast, and gastrointestinal cancers. Notably, in a cohort of 37 evaluable ovarian cancer patients, an objective response rate (ORR) of 24% was observed, including two complete responses. Incyte plans to initiate a phase 3 program for INCB123667 in 2025.
