Multikinase Inhibition with Tinengotinib in Advanced Solid Tumors: Results from a Multicenter Phase Ib/II Trial

Area of Science:

• Oncology
• Pharmacology
• Genomics

Background:

• Tinengotinib is a multikinase inhibitor targeting Aurora kinases, FGFRs, VEGFR-2, and JAKs.
• Advanced solid tumors often lack effective treatment options, necessitating novel therapeutic approaches.

Purpose of the Study:

• To evaluate the safety, pharmacokinetics, and efficacy of tinengotinib in patients with advanced solid tumors.
• To identify genomic correlates of response and resistance to tinengotinib treatment.

Main Methods:

• A phase Ib/II study enrolled patients with advanced/metastatic solid tumors at seven US sites.
• Tinengotinib was administered at 12 mg once daily (Arm A) and various doses/schedules (Arm C).
• Pharmacokinetic, safety, efficacy, and exploratory genomic analyses were performed.

Main Results:

• 197 patients received tinengotinib; 81.2% experienced treatment-related adverse events, most commonly hypertension.
• Clinical benefit was observed in 20.8% of evaluable patients, with notable objective response rates in prostate and breast cancers.
• Genomic analyses suggested correlations between FGFR2 fusions and response in cholangiocarcinoma, and identified potential associations with EGFR, MLL, and MYC alterations.

Conclusions:

• Tinengotinib demonstrated manageable toxicity and antitumor activity in advanced solid tumors.
• Infrequent hyperphosphatemia and ocular toxicities were noted.
• Integrated analyses support continued development and biomarker-informed precision oncology strategies.