Phase 2 trial of dalpiciclib plus cetuximab for HPV-negative, anti-PD-1 resistant recurrent or metastatic head and neck squamous cell carcinoma

HPV-negative head and neck squamous cell carcinoma (HNSCC) is characterized by activation of the CDK4/6 pathway. As immunotherapy has become the first-line treatment for HNSCC, resistance to anti-PD-1 agents is a challenge. A phase 2 trial at Shanghai Jiao Tong University School of Medicine (China) evaluated the combination of dalpiciclib (CDK4/6 inhibitor) and cetuximab (anti EGFR antibody) for anti-PD-1 resistant, HPV-negative, recurrent or metastatic (R/M) HNSCC. The primary endpoint was objective response rate (ORR). Twenty-eight patients were enrolled. The ORR was 68% (95% CI 49-82), which met the primary endpoint. With a median follow-up of 9.2 months (IQR 5.98-14.12), the median progression-free survival was 7.0 months (95% CI 4.13-NR) and the median overall survival was 17.0 months (10.75-23.25). Treatment-related adverse events occurred in all patients, predominantly grade 1 or 2. There were no grade 4 or 5 TRAEs. The authors conclude that the combination of dalpiciclib and cetuximab was well tolerated and showed promising efficacy in patients with anti-PD-1 resistant, HPV-negative R/M HNSCC.