Nimbus Therapeutics announced updated clinical and translational data from its Phase 1/2 trial of NDI-101150, a novel, oral, potent, and selective small-molecule hematopoietic progenitor kinase 1 (HPK1) inhibitor, for treating advanced solid tumors. The data, presented at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting, highlight the potential of NDI-101150 as a monotherapy, particularly in heavily pretreated renal cell carcinoma (RCC) patients. The trial (NCT05128487) assesses NDI-101150 both as a monotherapy and in combination with pembrolizumab in adults with advanced solid tumors.
NDI-101150 Demonstrates Encouraging Efficacy in RCC
Updated efficacy data from 17 response-evaluable patients with RCC who received NDI-101150 monotherapy showed an objective response rate of 18%, including one complete response and two partial responses. Furthermore, a clinical benefit rate (complete response + partial response + stable disease ≥6 months) of 29% and a disease control rate of 65% were observed. These results suggest that NDI-101150 has the potential to provide meaningful clinical benefit in a population with limited treatment options.
Safety and Tolerability
The safety profile of NDI-101150 was generally well-tolerated. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 14% of all patients exposed to NDI-101150 (n=88). The most common TRAEs were nausea, diarrhea, vomiting, and fatigue.
Mechanistic Insights
Analysis of tumor biopsies indicated a more robust presence of immune cells post-treatment, with increased numbers of tumor-infiltrating lymphocytes and dendritic cells in the tumor microenvironment. Comprehensive 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. "The objective responses and disease control rates seen thus far with NDI-101150 in heavily pretreated patients as well as the current safety profile support further evaluation of NDI-101150 in the clinic."
Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus, added, "The clinical and translational data package being presented at SITC demonstrates both the therapeutic potential of NDI-101150 and the power of our computational drug discovery engine to design highly selective molecules against challenging targets like HPK1. The monotherapy activity we observed is particularly noteworthy, as many second-generation immunotherapy compounds have struggled to show clinical benefit on their own. Together with its safety profile and the immune activation signals we’ve observed, these data support NDI-101150’s potential as a novel oral non-checkpoint immunotherapy option for patients who need new treatment approaches beyond current checkpoint inhibitors."
