Young Jun Kim, MD, PhD

YOUNG JUN KIM, MD, PhD, Co-Leader of the Translational Research and Interventional Oncology Research Program at Vanderbilt-Ingram Cancer Center in Nashville, was more guarded in his interpretation of the data, particularly focusing on the lack of clinical improvement in the combination cohort that targets programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte– associated protein 4 (CTLA-4), two different immune checkpoint inhibitors. 

“While there is some small clinical signal with durvalumab (Imfinzi) alone, this is seen in a cohort with low PD-L1 expression on the tumor, which this antibody is purported to target. This may point to the importance of PD-L1 expression on nontumor cells as a biomarker. Furthermore, other tumors—lung and melanoma—showed that the addition of CTLA-4 blockade in the form of ipilimumab (Yervoy) improved clinical response, whereas this head and neck cancer study used tremelimumab, another CTLA-4–blocking antibody, and this current study showed no improvement with the second agent. This suggests that the nonspecific portion of the antibody, the Fc [fragment crystallizable] region, may be important as well,” said Dr. Kim. “A depleting antibody such as a human immunoglobulin G1 (IgG1) may be more effective clinically than an IgG2 such as tremelimumab, which is a nondepleting antibody.” 

“That’s a variable we need to think about going forward,” Dr. Kim concluded. “A depleting antibody may make a big difference. There is active bioengineering research to defucosylate IgG1 antibodies to further improve their depletion function.” ■

DISCLOSURE: Dr. Kim reported no conflicts of interest.