Abstract 4352: Safety and pharmacokinetics of tinengotinib monotherapy in different doses and dosing schedules in advanced solid tumors

Abstract Background: Tinengotinib is a novel multi-kinase inhibitor that targets cell proliferation, angiogenesis, and immune-oncology pathways by inhibiting Aurora kinases A/B, Janus kinases (JAK) and receptor tyrosine kinases (FGFRs and VEGFRs). Here we present the safety and pharmacokinetics (PK) of tinengotinib monotherapy in different doses and dosing schedules from a multicenter, open label phase Ib/II study in patients (pts) with advanced solid tumors. Methods: Eligible pts received tinengotinib monotherapy in Arm A (12 mg once daily (QD)) and Arm C with QD doses of 5, 8, 10 and 12 mg, and twice daily (BID) doses of 4 mg and 6 mg every 28-day/cycle. Safety was assessed based on CTCAE v5.0. PK samples (plasma) were analyzed by liquid chromatography-tandem mass spectrometry. Preliminary efficacy including Objective Response Rate (ORR) was evaluated per RECIST 1.1. Results: 197 pts were enrolled and received tinengotinib monotherapy at the following doses and schedules: 4mg BID (n=18), 6mg BID (n=18), 5mg QD (n=14), 8mg QD (n=18), 10mg QD (n=21), and 12mg QD (n=108). Treatment-related Adverse Events (TRAE) were reported in 81.7% (161/197) pts: 46.2% were Grade (G) 3-4, 0% G5. The most common G3-4 TRAE (>10%) was hypertension. Increased G3-4 TRAE rates were seen at higher dose exposures, but no significant differences were noted between the BID and QD schedules. The maximum concentration (Tmax) was reached at ∼2-4 hr. The terminal elimination half-life (t1/2) was similar across all QD dose groups in the PK-run-in of Arm C, at ∼26-34hr. The apparent volume of distribution (Vz/F) is much larger than 100L. Steady state was reached at C1D15, with mean accumulation ratios of approximately 2-5. Exposure of tinengotinib increased with increasing dose up to 10mg QD, reaching potential saturation of absorption between 10mg and 12mg QD. No notable difference in AUC was observed in QD vs. BID schedules. Sensitivity analyses were like those of the main analysis. Among 159 efficacy evaluable subjects (n=15 in 4 mg BID; n=18 in 6 mg BID; n=10 in 5 mg QD; n=13 in 8 mg QD; n=19 in 10 mg QD; n=84 in 12 mg QD), the best overall response was 13.2% (21/159) including PRs in 2 (11.1%) pts in 6 mg BID, 1(10.0%) in 5 mg QD, 4 (21.1%) in 10 mg QD, and 13 (15.5%) in 12 mg QD. 1 CR was achieved in 12 mg QD. The dose level demonstrating superior efficacy was 10mg QD, with an ORR of 21.1%. Conclusions: There were no discernable trends in safety or PK between the BID and QD dose schedules. Although there was an increase in TRAEs with overall dose increase, the 10mg QD dose was shown to have an optimal PK profile and demonstrated superior efficacy as compared to the other dose levels. These results suggest that the combination of known PK and safety predictability with promising efficacy provides a basis of dose selection for further clinical development of tinengotinib. Clinical trial Information: NCT04742959 Citation Format: Sarina A. Piha-Paul, Sanjay Goel, Chih-Yi Liao, Nashat Y. Gabrail, Farshid Dayyani, Syed Kazmi, Sayeh Lavasani, Shumao Ni, Caixia Sun, Katie Hennessy, Hui Wang, Peng Peng, Jean Fan, Milind Javle. Safety and pharmacokinetics of tinengotinib monotherapy in different doses and dosing schedules in advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4352.