Multicenter phase 1b-2 trial of tinengotinib as monotherapy or combined with atezolizumab in advanced solid tumors

Tinengotinib is a spectrum-selective multikinase inhibitor targeting FGFR1-3, JAK1/2, VEGFRs, and Aurora A/B kinases. A multicenter phase 1b-2 trial in China evaluated tinengotinib as monotherapy (arm A; n=53) in 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-esclation phat with standard 3+3 design (phase 1b) followed by dose-expansion (phase 2). The primary endpoints of phase 1b were safety, tolerability, and dose selected for expansion, with secondary endpoints efficacy (phase 2) and pharmacokinetics. The trial met the prespecified primary endpoints: tinengotinib was well tolerated without dose-limiting toxicities, and the maximum tolerated dose was not reached. Tinengotinib demonstrated antitumor activity both as monotherapy (objective response rate in arm A 16.7%) and in combination with atezolizumab (ORR in arm B 22.6%). In predefined exploratory subgroup analysis, notable efficacy was observed in cholangiocarcinoma (ORR 30.8% in arm A and 25.0% in arm B). In patients with cholangiocarcinoma previously treated with immune checkpoint inhibitors, the combination regimen achieve an ORR of 20.0% and a disease control rate of 75.0%. The authors conclude that these findings support further development of tinengotinib, both as monotherapy and in combination with immunotherapy.