pf-07265028

PF-07265028 is a selective small molecule inhibitor of hematopoietic progenitor kinase 1 (HPK1, also known as MAP4K1), developed by Pfizer for the treatment of cancer. HPK1 is a negative regulator of T-cell receptor (TCR) signaling and plays a role in immunosuppression within the tumor microenvironment. By inhibiting HPK1, PF-07265028 aims to enhance anti-tumor immune responses by preventing HPK1-mediated inhibition of TCR signaling and reducing immunosuppression. The drug was advanced into phase 1 clinical trials as both monotherapy and in combination with sasanlimab (an anti-PD-1 antibody) for patients with advanced or metastatic solid tumors, including gastric cancer, gastroesophageal junction cancer, urothelial cancer, non-small cell lung cancer, and head and neck squamous cell carcinoma[2][3][4][7]. However, development was discontinued after phase 1[3][6].