The multi-kinase inhibitor tinengotinib as monotherapy or combined with atezolizumab in advanced solid tumors: a phase Ib/II trial

Tinengotinib is a spectrum-selective multi-kinase inhibitor targeting FGFR1-3, JAK1/2, VEGFRs, and Aurora A/B kinases. This phase Ib/II clinical trial (NCT05253053) evaluated tinengotinib as monotherapy (Arm A, n = 53, in Chinese patients with advanced solid tumors) and in combination with atezolizumab (Arm B, n = 31, in patients with advanced biliary tract cancer). Each arm comprised a dose-escalation phase with standard 3 + 3 design (phase Ib) followed by a dose-expansion phase (phase II). The primary endpoints of the phase Ib were safety, tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and dose selection for expansion, with secondary endpoints of efficacy (phase II) and pharmacokinetics. The trial met pre-specified primary endpoints: tinengotinib was well tolerated without DLTs, and MTD was not reached. Tinengotinib demonstrated antitumor activity both as monotherapy (objective response rate [ORR]: 16.7% in Arm A) and combined with atezolizumab (ORR: 22.6% in Arm B). In predefined exploratory subgroup analysis, notable efficacy was observed in cholangiocarcinoma (ORR: 30.8% in Arm A [n = 13]; 25.0% in Arm B [n = 28]). Tinengotinib monotherapy achieved favorable response in cholangiocarcinoma harboring FGFR2 fusion progressing on prior FGFR inhibitor (ORR: 66.7%). In patients with cholangiocarcinoma previously treated with immune checkpoint inhibitors (n = 20), the combination regimen achieved an ORR of 20.0% and a disease control rate of 75.0%. These findings support further development of tinengotinib, both as monotherapy and in combination with immunotherapy.