45O - First-in-human study of ABSK061: A selective fibroblast growth factor receptor (FGFR) 2/3 inhibitor for treating patients with advanced solid tumors

Background

Aberrant activation of FGFR signaling promotes cancer cell proliferation and tumor growth. Targeting FGFR2/3 selectively may alleviate FGFR1-dependent hyperphosphatemia and could provide better efficacy. Here, we evaluated the safety and pharmacokinetics of a selective and potent FGFR2/3 inhibitor ABSK061 in advanced solid tumors in a phase 1 open-label study (NCT05244551).

Methods

As of November 2023, a total of 28 patients with advanced solid tumors were enrolled in the escalation part of the study. These patients were treated with ABSK061 twice daily (5mg-100mg BID) or once daily (150mg QD) in 28-day cycles. 75mg BID and 150mg QD were selected to explore the recommended doses for expansion.

Results

Among the 28 patients, the mean age was 53.5 years with 54% males. When comparing 150mg QD with 75mg BID, 150mg QD resulted in ∼50% higher C_max,ss, ∼50% lower C_trough,ss and similar AUC_0-24h,ss. No dose-limiting toxicity was observed. The most common treatment-related adverse events (TRAEs) (≥15%) included alanine aminotransferase (ALT) increase, aspartate aminotransferase (AST) increase, and anaemia. Grade ≥3 TRAE was reported in 5 patients, including anaemia, ALT increase, AST increase, bilirubin conjugated increase, blood bilirubin increase, gamma-glutamyltransferase increase, and pulmonary embolism. Hyperphosphatemia was reported in only 11% (3/28) of patients, and all were grade 1. One patient on 75mg BID experienced pulmonary embolism with a prior history, discerned as an unlikely related serious adverse event (SAE) by the investigators. Among the 5 patients with prior treatments and FGFR2 fusion/amplification or FGFR3 fusion, 2 achieved partial response (PR) and 2 achieved stable disease (SD). Objective response rate was 40%. All 4 patients are continuing treatment. Disease control rate was 80%. PR was observed in non-small cell lung cancer (FGFR2 fusion) and urothelial carcinoma (FGFR3 fusion).

Conclusions

This study demonstrated the anti-tumor activity of ABSK061 in patients with FGFR2/3 alterations and its favorable safety profile, which warrants further investigation.

Clinical trial identification

NCT05244551.

Editorial acknowledgement

Legal entity responsible for the study

Abbisko Therapeutics Co., Ltd.

Funding

Abbisko Therapeutics Co., Ltd.

Disclosure

Z. Wang, Z. Zhang, P. Zhang, Y. Wang, J. Zhang: Other, Personal, Full or part-time Employment: Abbisko Therapeutics Co. Ltd. All other authors have declared no conflicts of interest.