Dr. Davar on the Rationale for the Combination of Anti-TIM-3 and Anti-PD-1

Diwakar Davar, MD, assistant professor of medicine, Department of Medicine, Hematology/Oncology, University of Pittsburgh, discusses the rationale for the combination of anti-TIM-3 and anti-PD-1 in multiple tumor types.

In a phase 1 study presented at the 2018 SITC Annual Meeting, Davar presented preliminary results of TSR-022, an anti-TIM-3 monoclonal antibody, in combination with TSR-042, an anti-PD-1 agent, in patients with colorectal cancer (CRC), post-PD-1 non—small cell lung cancer, and melanoma.

TIM-3 is highly coexpressed alongside PD-1 and may represent a resistance mechanism, especially in patients who do not respond to checkpoint blockade, says Davar. TIM-3 coexpression has been noted in several cancers, including melanoma and lung cancer. This serves as proof-of-concept to evaluate TIM-3 and PD-1 dual blockade in patients who have PD-1—refractory tumors.

The combination is also being evaluated in patients with CRC, although data from that cohort has yet to report. However, Davar notes that promising data were presented at the 2018 SITC meeting from the melanoma and lung cancer cohorts. According to Davar, investigators noted a positive relationship between dosing and efficacy with the combination in those patient subsets.