Nimbus Therapeutics presented updated data from its Phase 1/2 clinical trial of NDI-101150, a novel oral HPK1 inhibitor, at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting. The data demonstrated promising monotherapy activity in heavily pretreated renal cell carcinoma (RCC) patients, including those with prior checkpoint inhibitor exposure.
NDI-101150 Monotherapy Shows Encouraging Results in RCC
The Phase 1/2 open-label trial (NCT05128487) evaluated NDI-101150 as a monotherapy and in combination with pembrolizumab in adults with advanced solid tumors. The presented results included safety data from 53 patients in dose escalation cohorts and efficacy data from 17 response-evaluable RCC patients treated with NDI-101150 monotherapy. As of August 12, 2024, the data indicated:
- An 18% objective response rate (3/17 patients) in response-evaluable RCC patients, including one complete response and two partial responses.
- A clinical benefit rate (CR + PR + stable disease ≥6 months) of 29% (5/17 patients).
- A disease control rate of 65% (11/17 patients).
Safety and Target Engagement
NDI-101150 was generally well-tolerated, with immune-related adverse events supporting the proposed mechanism of action. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 14% of all patients (n=88), with the most common TRAEs being nausea, diarrhea, vomiting, and fatigue. The data also confirmed that NDI-101150 effectively inhibited its target across multiple dose levels, providing pharmacodynamic evidence of the molecule's activity.
Mechanistic Insights
Analysis of tumor biopsies showed a more robust presence of immune cells post-treatment, with increased numbers of tumor-infiltrating lymphocytes and dendritic cells in the tumor microenvironment. Gene expression profiling demonstrated broad activation of immune-related pathways, including enhanced interferon response and T cell activation signals.
Expert Commentary
"These clinical results of NDI-101150 are highly encouraging, particularly in the context of renal cell carcinoma patients who have experienced disease progression on prior checkpoint inhibitors," said Nathalie Franchimont, M.D., Ph.D., Chief Medical Officer of Nimbus. Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus, added, "The monotherapy activity we observed is particularly noteworthy, as many second-generation immunotherapy compounds have struggled to show clinical benefit on their own."
About NDI-101150 and HPK1
NDI-101150 is a novel, oral, potent, and selective small-molecule hematopoietic progenitor kinase 1 (HPK1) inhibitor. HPK1 is a kinase that plays a role in regulating immune cell function. Inhibiting HPK1 can enhance immune responses against tumors.
