Dr Goel on the Safety Profile 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 safety profile of the TKI tinengotinib (TT-00420) as a monotherapy and in combination with chemotherapy in patients with solid tumors.

A phase 1b/2 trial (NCT04742959) evaluated tinengotinib in 2 monotherapy arms, as well as in 1 combination arm alongside nab-paclitaxel (Abraxane), in adult patients with pretreated solid tumors who have no available standard therapeutic treatment options. Tinengotinib is a multi-kinase inhibitor, with targets such as JAK, Aurora kinases A/B, FGFRs, and VEGFRs.

Since tinengotinib targets multiple kinases, it is associated with several common treatment-related adverse effects (TRAEs), Goel says. Among the 172 patients in the trial’s 2 monotherapy arms, 73.8% experienced any-grade TRAEs. Grade 1, 2, and 3 TRAEs were observed in 14.5%, 22.1%, and 36.0% of patients in the monotherapy arms, respectively. In addition, 1.2% of patients had grade 4 TRAEs, and no grade 5 TRAEs occurred. The grade 4 TRAEs included increased alanine transaminase, increased aspartate transaminase, and perforation of the large intestine. The investigators reported no treatment-related deaths. Overall, the most common TRAEs in the monotherapy arms were hypertension (32.0%), stomatitis (22.1%), diarrhea (16.3%), palmar-plantar erythrodysesthesia syndrome (14.0%), nausea (12.8%), and fatigue (10.5%).

The 5 patients who received tinengotinib plus nab-paclitaxel experienced more myelosuppression than those in the monotherapy arms, Goel notes. In total, 80.0% of patients in this arm experienced tinengotinib-related adverse effects. Common TRAEs in this arm included neutropenia and stomatitis, which each occurred in 60% of patients, as well as hyponatremia, hypokalemia, and hypertension, which each occurred in 40% of patients. One patient in the combination arm died from a pulmonary hemorrhage, which was not considered related to the study drug.

The AEs seen across both arms are commonly associated with TKIs and were expected, Goel concludes.