Michael Morse, MD

FORMAL DISCUSSANT of the abstract presented by Harding et al, Michael Morse, MD, Professor of Medicine at Duke University Medical Center, in Durham, North Carolina, noted that the authors should be commended on a complex dose-escalation strategy that surely required a lot of collaboration among the different sites.

“This is a very interesting abstract and an example of the direction the field is moving in to try to expand therapies for patients with more difficult-to-treat cancers,” said Dr. Morse. “There are numerous causes of primary and secondary resistance to immune checkpoint blockade that will need to be addressed in specific ways.” According to Dr. Morse, because finding a single methodology that will work for all patients remains unlikely, it’s important to have alternative immune checkpoints beyond programmed cell death protein 1 (PD-1).

“There’s obviously enthusiasm in the field,” he said. “There are at least six other antibodies in development targeting T-cell immunoglobulin domain and mucin domain–containing molecule 3 (TIM-3), and at least one of them is a bispecific antibody against PD-1 and TIM-3. Nevertheless, there are limited data for these early studies that are also beginning to combine checkpoint inhibitors.”

Despite the enthusiasm, Dr. Morse cautioned that TIM-3 is a complicated target, with multiple binding partners and expression by multiple cells. “It may be working in different ways in different cancers and perhaps differently in combination with other checkpoint molecules,” said Dr. Morse. “We really do need to get data from the tissue level to understand this better, and we eagerly await the combination data.” ■

DISCLOSURE: Dr. Morse is a consultant with Genentech, Eli Lilly, Eisai, Lexicon, Novartis, Ipsen, Bayer, Sanofi, IVT, Gritstone, Celldex, and Taiho and has received research funding from BMS, Merck, Ipsen, Eisai, MedImmune/AstraZeneca, and Aslan.