Document Information Content Entity Continuant Continuant Abstract Entity Entity Generically Dependent Continuant 2025-06-24T18:50:53 RDF description of Phase 1/2 trial of the HPK1 inhibitor NDI-101150 as monotherapy and in combination with Pembrolizumab: clinical update [abstract] - http://repository.healthpartners.com/individual/document-rn37066 <p>Background: NDI-101150 is a potent, selective, oral inhibitor of hematopoietic progenitor kinase 1 (HPK1), with a different immunotherapy mechanism to other checkpoint inhibitors. NDI-101150 reactivates anti-tumor activity of T-cells, B-cells and dendritic cells (DCs), even under immunosuppressive conditions.<br>Methods: Safety and preliminary efficacy (primary endpoints) of NDI-101150 alone (50�200 mg once-daily in 28-day cycles) and in combination with pembrolizumab are being assessed in patients (pts) with relapsed or metastatic solid tumors. NDI-101150 monotherapy expansion cohorts in renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and gastric/gastroesophageal (G/GEJ) cancer are also being assessed.<br>Results: Dose escalation/expansion data as of Dec 13, 2023 are presented. Treatment (tx)-related adverse effects (TRAEs) in the safety set (N=39) for NDI-101150 monotherapy are presented in the table. 30 (76.9%) pts reported � 1 TRAE and 5 (12.8%) pts reported grade � 3 TRAEs. Most common TRAEs were nausea, vomiting, diarrhea and fatigue. Combination tx TRAEs (N=7) recapitulate the monotherapy profile (data not shown). NDI-101150 induced clinical benefit in 4/24 (16.7%) response-evaluable pts: complete response in 1 pt with clear cell RCC; stable disease (SD) � 6 months in 3 pts (RCC [21 months], pancreatic cancer and endometrial cancer). Unconfirmed SD was noted in 2 pts with RCC, and in 1 pt each with NSCLC and G/GEJ cancer. Nearly dose-proportional increases in exposure were observed on Day 1 of Cycle 1 (C1) across 50�200 mg, with steady state achieved between Days 15 and 28 of tx. Pharmacokinetic profiles of monotherapy and combination tx cohorts were similar. Sustained inhibition of pSLP76 of >50% relative to pre-tx levels (predicted to achieve efficacy in nonclinical models) was observed at all doses tested by Day 15 of C1. Using a custom 12-plex immunofluorescence assay to monitor changes in the tumor immune microenvironment, an on-tx biopsy assessment from a pt with RCC showed increased infiltration of activated CD8+ T-cells and DCs compared to archival biopsy, aligning with the proposed mechanism of action.<br>Conclusions: The observed clinical benefit and safety profile support continued evaluation of NDI-101150 as a viable next-generation immunotherapeutic. Clinical trial information: NCT05128487.<p> Cancer 22922 internal-pdf://0408702770/Phase 1-2 trial of the HPK1 inhibitor NDI-1011.pdf document-rn37066 Journal of Clinical Oncology 39544 abstract 10.1200/JCO.2024.42.16_suppl.30 Drugs and Drug Therapy Clinical Trials Suppl 16 public 2024-08-31T22:03:57.593-05:00 Phase 1/2 trial of the HPK1 inhibitor NDI-101150 as monotherapy and in combination with Pembrolizumab: clinical update [abstract] 42