ESMO Congress 2024 | OncologyPRO

Abstract 635P

Background

TSN084 is a unique type II multi-kinase inhibitor, which can overcome the acquired drug resistance of cMet, Trks, and Flts and also inhibit other oncotargets including Axl, DDRs, and CDK8/19. It demonstrated potent anti-proliferation activity against many tumor cell lines, and also effectively inhibited tumor growth in several CDX drug-resistant models.

Methods

This phase 1 study was to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), safety and PK profiles, antitumor activity and effect on biomarkers of TSN084 (NCT06386705). The dose-escalation scheme combines both accelerated titration and traditional ’3+3’ design. Patients will receive TSN084 orally, once daily (QD), until disease progression (PD) or unacceptable toxicity.

Results

As of April 28, 2024, 19 patients with refractory advanced tumors had been treated with doses of 20-200 mg QD (15 NSCLC, 2 adenoid cystic carcinoma, 1 each for gastric cancer and mediastinal teratoma). Median treatment duration was 46 (range 26-189) days. No dose limiting toxicity was observed. The most common (≥ 10%) treatment related adverse events (TRAEs) were hypoalbuminemia and blood creatine phosphokinase MB increased (31.6% each), ALT increased (26.3%), AST and bilirubin conjugated increased (21.1% each), decreased appetite, fatigue, vomiting and weight decreased (10.5% each). Except one case of fatigue (grade 3), no other TRAEs of grade ≥ 3 were reported. MTD had not been reached and the dose escalation was ongoing. Among 12 evaluable patients per RECIST 1.1, 7 (58.3%) had stable disease (SD) and 5 (41.7%) PD. In 5 evaluable patients with MET exon 14 skipping mutant NSCLC who failed prior MET inhibitors, 3 (60.0%) had SD (tumor shrinkage up to -23%) and 2 (40.0%) PD; serial assessment of ctDNA showed significant declines in MET VAF after treatment among the patients who obtained tumor shrinkage. TSN084 was absorbed with Tmax around 2.7 hours and half-life around 28 hours. PK data indicated good dose proportionality in exposure with no obvious accumulation.

Conclusions

TSN084 was well tolerated at doses up to 200 mg and demonstrated preliminary anti-tumor activity in advanced malignant tumors. Further investigations in targeted indications are warranted.

Clinical trial identification

NCT06386705.

Editorial acknowledgement

Legal entity responsible for the study

Tyligand Bioscience (Shanghai) Limited.

Funding

Tyligand Bioscience (Shanghai) Limited.

Disclosure

J. Li, C. Dong, L. Lai, S. Ma, B. Zhong, T. Zhang: Financial Interests, Personal, Full or part-time Employment: Tyligand Bioscience (Shanghai) Limited. All other authors have declared no conflicts of interest.