Multicenter phase 1b-2 trial of the multikinase inhibitor tinengotinib in advanced solid tumors

Tinengotinib is a multikinase inhibitor targeting aurora kinases A/B, FGFRs 1-3, VEGFR-2, and Janus kinases 1-2. A phase 1b-2 trial at seven centers in the USA evaluated tinengotinib for patients with advanced solid tumors. Patients lacking standard treatment options received tinengotinib 12 mg once daily in Arm A and at multiple dose levels/dosing schedules in arm C. Among 197 patients receiving tinengotinib, treatment-emergent adverse events occurred in 160 (81.2%), most commonly hypertension. Hyperphosphatemia and ocular toxicities were uncommon. Clinical benefit was achieved by 33 of 159 evaluable patients (20.8%), including one complete response, 20 partial responses, and 12 stable diseases ≥ 6 months. Antitumor activity was most pronouced with 10-mg and 12-mg dose levels. The objective response rate was 33.3%, 30.0%, and 13.0% in prostate cancer (n=15), breast cancer (n=20), and cholangiocarcinoma (n=23), respectively. Exploratory genomic analyses identified potential molecular correlations of response, including FGFR2 fusions in cholangiocarcinoma responders. The authors conclude that tinengotinib demonstrated manageable toxicity with antitumor activity across advanced solid tumors.