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

作者：Panpan Zhang, Yanru Qin, Jifang Gong, Yongsheng Wang, Kunyu Yang, Yongsheng Li, Guanghai Dai, Ji Zhu, Sha Sha, Ming Tong, Xuebin Liao, Lin Shen · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.16_suppl.2590 · 被引用次数：3 · 研究领域：Drug Transport and Resistance Mechanisms、Prostate Cancer Treatment and Research、Colorectal Cancer Treatments and Studies

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 tre...