Dr Goel on the Mechanism of Action of Tinengotinib in Solid Tumors

Sanjay Goel, MD, MS, director, Phase I/Investigational Therapeutics, Rutgers Cancer Institute of New Jersey; professor, medicine, Division of Medical Oncology, Section of Solid Tumors, Rutgers Robert Wood Johnson Medical School, discusses the mechanism of action of tinengotinib (TT-00420) and the efficacy of this agent in patients with cholangiocarcinoma.

A phase 1b/2 trial (NCT04742959) investigated the TKI tinengotinib in adult patients with pretreated solid tumors who have no available standard therapeutic treatment options and adequate organ function. This included 17 patients with cholangiocarcinoma. The 3-arm trial evaluated the agent as a monotherapy, in combination with nab-paclitaxel, and as monotherapy in a pharmacokinetics run-in arm. The end points of this trial were safety and tolerability per CTCAE v5.0, preliminary efficacy per RECIST v1.1, clinical pharmacokinetics analyses, and biomarkers. In the overall evaluable trial population, the best overall response rate was 14.5%, the disease control rate was 64.5%, and the clinical benefit rate was 25%.

The small molecule inhibitor tinengotinib is a spectrum-selective multi-kinase inhibitor, Goel says. Its common targets include Aurora kinase A/B, JAK, FGFRs, and VEGFRs, Goel explains. By inhibiting these kinases, this agent targets angiogenesis, cell proliferation, and immune-oncologic pathways, Goel emphasizes.

In the subgroup of patients with cholangiocarcinoma, 17.6% (n = 3) achieved a partial response. Five patients in the cholangiocarcinoma subgroup had disease harboring an FGFR alteration. Although FGFR alterations in cholangiocarcinoma are not common, they are important to test for because patients with these alterations may be eligible for FDA-approved therapies, according to Goel. Among the 5 patients with FGFR-altered cholangiocarcinoma, 40% (n = 2) responded with tinengotinib. Moreover, 4 of those 5 patients had previously been exposed to prior FGFR-targeted therapy. These findings indicate that tinengotinib can benefit patients with FGFR-altered cholangiocarcinoma, including those who have received a prior FGFR-targeted agent, Goel concludes.

Disclosures: Dr Goel reports receiving honoraria from Amgen and Merck; he has stock and other ownership interests with Johnson and Johnson, Merck, and Moderna Therapeutics; he received institutional research funding from BeiGene, Deciphera, Dragonfly Therapeutics, EMD Serono, PharmaMar, Takeda, and TLC PharmaChem; he has a patent with co-inventor, John Mariadason, Ph.D, entitled "Method Of Determining The Sensitivity Of Cancer Cells To EGFR Inhibitors Including Cetuximab, Panitumumab And Erlotinib.", Patent No. 20090258364.