Reference Detail

Ref Type

Abstract

PMID

Authors

J. Zhu Z. Song Y. Zhao J. Zhang Y. Li D. Li R. Schneider Y. Ding Z. Sun Y. Qin Z-W. Chang Z. Wang Z. Zhang P. Zhang Y. Wang J. Zhang

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
ESMO Open	9	Supplement 1	February 2024	102274	ESMO Open

URL

https://www.esmoopen.com/article/S2059-7029(24)00042-5/fulltext

Abstract Text

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 Cmax,ss, ∼50% lower Ctrough,ss and similar AUC0-24h,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.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
ABSK061	ABSK061	2	1

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
ABSK061		ABSK-061\|ABSK 061	FGFR2 Inhibitor 23 FGFR3 Inhibitor 19	ABSK061 inhibits FGFR2 and FGFR3, potentially leading to antitumor activity (ESMO Open 9 (2024): 102274).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
FGFR3 fusion	transitional cell carcinoma	predicted - sensitive	ABSK061	Phase I	Actionable	In a Phase I trial, ABSK061 treatment resulted in a partial response in a patient with urothelial carcinoma harboring an FGFR3 fusion (ESMO Open 9 (2024): 102274); NCT05244551).	detail...
FGFR2 fusion	lung non-small cell carcinoma	predicted - sensitive	ABSK061	Case Reports/Case Series	Actionable	In a Phase I trial, ABSK061 treatment resulted in a partial response in a patient with non-small cell lung cancer harboring an FGFR2 fusion (ESMO Open 9 (2024): 102274); NCT05244551).	detail...