HPK1 inhibitor NDI-101150 as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: Phase 1/2 trial results

Authors

• David A Braun
• Marcus S Noel
• Ryan H Moy
• Kurt Demel
• Martin Gutierrez
• Sunil Sharma
• Arif Hussain
• Shirish M. Gadgeel, Henry Ford HealthFollow
• Julio Peguero
• Toni K Choueiri
• Hamid Emamekhoo
• Brian Van Tine
• Rama Balaraman
• GiNell Elliott
• Sritama Nath
• Scott R Daigle
• Pavan Kumar
• Anita Scheuber
• David Sommerhalder

Recommended Citation

Braun DA, Noel MS, Moy RH, Demel K, Gutierrez M, Sharma S, Hussain A, Gadgeel S, Peguero J, Choueiri TK, Emamekhoo H, Van Tine B, Balaraman R, Elliott G, Nath S, Daigle SR, Kumar P, Scheuber A, Sommerhalder D. HPK1 inhibitor NDI-101150 as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: Phase ½ trial results. Cell Rep Med. 2026;7(5):102789.

Document Type

Article

Publication Date

5-19-2026

Publication Title

Cell Rep Med

Keywords

Humans, Antibodies, Monoclonal, Humanized, Female, Male, Middle Aged, Protein Serine-Threonine Kinases, Aged, Neoplasms, Protein Kinase Inhibitors, Antineoplastic Combined Chemotherapy Protocols, Adult, Tumor Microenvironment, Carcinoma, Renal Cell, Dendritic Cells, Maximum Tolerated Dose

Abstract

Hematopoietic progenitor kinase 1 (HPK1) induces potent anti-tumor immunity in preclinical models by activating and recruiting T cells, B cells, and dendritic cells into the tumor microenvironment (TME). Here, we evaluate NDI-101150, a potent, selective HPK1 inhibitor, in a phase ½ trial as a monotherapy or in combination with pembrolizumab in patients with advanced solid tumors. The monotherapy maximum tolerated dose (MTD) is 150 mg once daily, and doses tested up to 100 mg once daily are combinable with pembrolizumab without reaching an MTD. In clear cell renal cell carcinoma, the investigator-assessed overall response rate with monotherapy treatment is 13.6%, including one complete response and two partial responses, with a clinical benefit rate of 27.3% and a disease control rate of 54.5%. Pharmacodynamic analyses show pharmacodynamic biomarker phospho-SLP76 inhibition and increased activated CD8(+) T cells and dendritic cells in the TME, supporting continued development (clinical registration number NCT05128487).

Medical Subject Headings

Humans; Antibodies, Monoclonal, Humanized; Female; Male; Middle Aged; Protein Serine-Threonine Kinases; Aged; Neoplasms; Protein Kinase Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Adult; Tumor Microenvironment; Carcinoma, Renal Cell; Dendritic Cells; Maximum Tolerated Dose

PubMed ID

42097144

Volume

7

Issue

5

First Page

102789

Last Page

102789