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

Authors

null

Panpan Zhang

Peking University Cancer Hospital and Institute, Beijing, China

Panpan Zhang , Yanru Qin , Jifang Gong , Yongsheng Wang , Kunyu Yang , Yongsheng Li , Guanghai Dai , Ji Zhu , Sha Sha , Ming Tong , Xuebin Liao , Lin Shen

Organizations

Peking University Cancer Hospital and Institute, Beijing, China, The First Affiliated Hosital of Zhengzhou University, Zhengzhou, China, Department of Gastrooncology, Beijing Cancer Hospital, Beijing, China, West China Hospital, Sichuan University, Chengdu, China, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Chongqing Cancer Hospital, Chongqing, China, Chinese People’s Liberation Army General Hospital, Beijing, China, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China, Zhuhai Yufan Biotechnologies Co, Ltd, Guangdong, China, Tsinghua University, Beijing, China

Research Funding

Zhuhai Yufan Biotechnologies Co., Ltd, Guangdong, China

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.

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2024 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics—Immunotherapy

Track

Developmental Therapeutics—Immunotherapy

Sub Track

New Targets and New Technologies (IO)

Clinical Trial Registration Number

NCT05315167

Citation

J Clin Oncol 42, 2024 (suppl 16; abstr 2590)

DOI

10.1200/JCO.2024.42.16_suppl.2590

Abstract #

2590

Poster Bd #

69

Abstract Disclosures