A phase I/II study to evaluate the safety, pharmacokinetics, and efficacy of PRJ1-3024 in patients with advanced solid tumors.

2590 Background: PRJ1-3024 is a small molecule hematopoietic progenitor kinase 1 (HPK1) inhibitor designed to potentiate T-cell function. It was demonstrated that HPK1 activity suppresses immune functions of a wide range of cells including cluster of differentiation CD4 + , CD8 + T cells and dendritic cells (DCs), mediates T-cell dysfunction and is a potential therapeutic target for T-cell-based immunotherapies. These results strongly support inhibitor of HPK1 functioning as a potential cancer immunotherapy agent. Methods: This is a multicenter, open-label study. Primary objective of phase I study is to determine the maximum tolerated dose and recommended Phase 2 dose. Secondary objectives are to evaluate safety, PK, and efficacy of PRJ1-3024. It is dosed orally once daily. Dose-limiting toxicity (DLT) assessment to be completed after 24 days (from the first dose to the end of Cycle 1 continuous 21 medication days). Exploratory analysis of pharmacodynamic targets including multiple cytokines, SLP-76 phosphorylation, cfDNA and IgG typing. Results: As of Dec. 22, 2023, 30 patients were enrolled in 6 dose cohorts: 80, 160, 300, 320, 500, and 700mg. Median age was 59 years (range 36-69). Diagnoses were NSCLC (9), Melanoma (3), TNBC (3), Gastric Cancer (3), HNSCC (3), Esophagus Carcinoma (2), Colon Cancer (2), and other types (5). The most common TEAEs (in ≥2 pts) were diarrhea (12), vomiting (12), nausea (9), proteinuria (8), loss of appetite (6), etc. No DLT events, irAEs or treatment-related deaths occurred in all dose cohorts. 9 subjects reported SAEs, only 2 cases were evaluated to be probably related (6.7%), namely ‘myocardial ischemic’ and ‘acute kidney injury’. 1 melanoma subject achieved sustained PR, had been on treatment for more than 7 months up to now. 4 subjects achieved SD (1 NSCLC, 1 HNSCC, 2 TNBCs). PK and PD assessments will be released in due course. Conclusions: PRJ1-3024 is shown to be well tolerated in Chinese advanced solid tumor patients. Further safety and efficacy results would be presented at the conference. Clinical trial information: NCT05315167 .