Abstract CT118: Phase I dose escalation of ASKC202, a novel cMET tyrosine kinase inhibitor, in patients with advanced solid tumors
Authors: Song Tingting , Zhou Caicun , Li Wei , Li Xingya , Wu Lin , Zeng Shan , Miao Liyun , Liu Baogang , Wei Xuyu , Chen Jing , Han Luwei 
Published: April 2024

Abstract
Background ASKC202 is an oral and highly selective small molecule inhibitor which inhibits mesenchymal-epithelial transition. We report preliminary safety and efficacy data from an ongoing Phase I, FIH, dose-escalation study of ASKC202 in patients (pts) with advanced solid tumors (NCT05306132).
Methods A two-part study was initiated to evaluate MTD, safety and tolerability, pharmacokinetics and preliminary antitumor activity of ASKC202, including dose escalation study (Part A) and dose expansion study (Part B). Responses were assessed per RECIST 1.1 every 2 cycles (6 weeks). AEs were graded using CTCAE v5.0.In Part A, dose escalation followed the accelerated titration combined with the "3+3" design. Patients with heavily pre-treated solid tumors received ASKC202 orally at doses of 50, 150, 300, 450 and 600 mg/day once daily. The treatment continued until disease progression, unacceptable toxicity or treatment termination. If the subject in the 50mg dose group developed DLT, the dose group was switched to a "3+3" design.
Results As of November 30, 2023, 16 patients who are refractory or don’t respond to standard therapy were available received ASKC202 (50mg: N=1; 150mg: N=3; 300mg: N=6; 450mg: N=3; 600mg: N=3). 15/16 pts had pathological confirmation of non-small-cell lung cancer (except for 1 case of PSC). 8/16 pts had brain metastasis. 10/16 pts had cMET dysregulation including MET amplification (N=9; gene copy number 1.3-8.3) and MET missense mutation (N=1; p.S186L) with no patient having Exon 14 skipping mutation.ASKC202 was well-tolerated in all patients. No dose-limiting toxicity was observed in all dose levels (50 to 600 mg). The common TRAEs occurring in more than 20% of patients included: anemia (5/16), blood glucose elevation (5/16), ALT elevation (4/16),
AST elevation (4/16) and peripheral edema (4/16). Grade 3 TRAEs were only observed in one patient (300mg QD), including anemia and hypokalemia. Among 14pts who had at least one post-baseline anti-tumor assessment, 5 pts achieved a confirmed partial response. The confirmed ORR is 35.7%. The median best percentage change in target lesion size from baseline (depth of response) was 51.8% and 3pts had duration of tumor response ≥ 6 months. ORR and DCR for patients with cMET alteration (N=8) was 62.5% (5/8) and 75.0% (6/8) respectively. One subject (150mg QD) with MET missense mutation (p.S186L) had a 67% tumor reduction in intracranial lesion from baseline. Exposure of ASKC202 increased dose-proportionally at dose range 50mg to 300mg, but less than dose-proportionally increased at 300mg to 600mg.
Conclusions ASKC202 monotherapy was well-tolerated with manageable safety profile and showed anti-tumor signal and the central nervous system efficacy.
Citation Format: Tingting Song, Caicun Zhou, Wei Li, Xingya Li, Lin Wu, Shan Zeng, Liyun Miao, Baogang Liu, Xuyu Wei, Jing Chen, Luwei Han. Phase I dose escalation of ASKC202, a novel cMET tyrosine kinase inhibitor, in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT118.