HPK1 inhibitor NDI-101150 shows safety and antitumour activity in ccRCC

Dr Braun talks to ecancer at ASCO 2025 about an ongoing phase 1/2 trial evaluating NDI-101150, an oral inhibitor of hematopoietic progenitor kinase 1 (HPK1), as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors, focusing on clear cell renal cell carcinoma (ccRCC).

Among 29 ccRCC patients treated with NDI-101150 monotherapy, the drug demonstrated a manageable safety profile with common adverse events including nausea, diarrhoea, and fatigue, and a maximum tolerated dose identified at 150 mg. The objective response rate was 15%, with a clinical benefit rate of 25% and disease control rate of 60%, despite patients having received multiple prior therapies.

Pharmacodynamic analyses confirmed robust target engagement and immune activation within tumors, evidenced by increased infiltration of activated CD8+ T-cells and dendritic cells. These results support further development of NDI-101150 as a promising oral immunotherapy for ccRCC, alone or combined with other agents.