KEY TAKEAWAYS
- The phase I/II trials aimed to evaluate the safety, tolerability, target engagement, and preliminary anti-tumor activity of NDI-101150 monotherapy in relapsed/metastatic solid tumor patients.
- The primary objectives were to determine the RP2D and MTD.
- Early NDI-101150 monotherapy data showed promise for solid tumors, with ongoing research delving deeper into clinical response, drug dynamics, and immune impacts.
NDI-101150, an innovative oral inhibitor targeting HPK1, a MAP4K family kinase regulating T cells, B cells, and dendritic cells, is designed to boost immune responses and demonstrate anti-tumor effects, both independently and in synergy with immune checkpoint therapies.
David Sommerhalder and his research team aimed to assess the safety and efficacy of NDI-101150 through dose escalation and expansion, both as a standalone treatment and in combination with pembrolizumab. This report focuses on presenting the monotherapy data from the ongoing investigation.
Patients with relapsed and metastatic solid tumors underwent daily administration of escalating doses of NDI-101150 using a 3+3 cohort design. The study focussed on determining the recommended phase 2 dose(s) (RP2D) and the maximum tolerated dose (MTD) as primary objectives. Secondary objectives included safety assessment, characterization of pharmacokinetic (PK) profiles, and initial exploration of antitumor activity. Exploratory analyses involved evaluating proximal pharmacodynamic (PD) target engagement of HPK1, measured through phosphorylated SLP76 (pSLP76).
About 22 subjects were enrolled across four dose levels, with 81.8% experiencing at least one treatment-related adverse event (TRAE). Serious TRAEs occurred in 13.6% of subjects, and the most common TRAEs were vomiting, nausea, diarrhea, and fatigue, mostly Grade 1 or 2. Immune-related AEs were observed in 18.2% of subjects, but no treatment-related deaths occurred. Dose level 4 was deemed non-tolerated, with 2 out of 6 patients experiencing dose-limiting toxicities (DLTs) (Grade 3 pneumonitis and Grade 3 acute kidney injury). There was a nearly dose-proportional increase in Cmax/AUC.
The PD results showed over 50% reduction of pSLP76 in each cohort by Cycle 1 Day 15. Notably, a patient with renal cell carcinoma (RCC) in cohort 1 achieved a complete response, lasting 9 months. Two additional patients in cohorts 3 and 4 with RCC and pancreatic cancer experienced prolonged stable disease, with evidence of tumor shrinkage and response in CA 19.9. They remain on treatment at 13 and 9 months, respectively. Monotherapy dose optimization and combination dose escalation are currently ongoing.
The study showed early promise in advanced solid tumor patients. Initial trials indicate good safety, targeted action against the intended immune protein, and hints of anti-tumor activity even when used alone. Further research will delve deeper into its clinical effects, drug behavior, and immune system impact. Research is sponsored by Nimbus Saturn, Inc.
Source: https://jitc.bmj.com/content/11/Suppl_1/A847
Clinical Trial: https://clinicaltrials.gov/study/NCT05128487
Sommerhalder D, Noel M, Boiko S, et al. (2023). ’’ Monotherapy results from an ongoing phase 1a dose escalation study of NDI-101150, a highly selective oral hematopoietic progenitor kinase 1 (HPK1) inhibitor.’’ Presented at SITC 2023 (751).
