Expert Explains Rationale Behind RELATIVITY-047 in Melanoma

LAG-3 represents a potentially relevant immune checkpoint pathway, according to Hussein A. Tawbi, MD, PhD.

In an interview with Oncology Nursing News®, Tawbi, who is a professor of melanoma medical oncology of The University of Texas MD Anderson Cancer Center, deputy chair of clinical research, co-director of MD Anderson Brain Metastases Clinic, as well as lead study author in a recent study published in the New England Journal of Medicine, discussed the results of the RELATIVITY-047 trial (NCT03470922), which found that the combination of the immune checkpoint inhibitors relatlimab and nivolumab (Opdivo) demonstrated safety and efficacy as a treatment for patients with untreated, advanced melanoma. ¹

Specifically, patients who received the combination achieved a median progression-free survival (PFS) of 10.1 months (95% CI, 6.4-15.7) compared with 4.6 months (95% CI, 3.4-5.6) among patients who received nivolumab as monotherapy (HR, 0.75; 95% CI, 0.62-0.92; P = .006).

Tawbi explained that “LAG-3 is one of several checkpoint inhibitors that are expressed on immune cells—in this case specifically on activated exhausted T cells. And as you know, you know, the immune checkpoint inhibitors have been you have revolutionized cancer in the last decade.”

“One of the challenges with the combination of PD-1 and CTLA-4 is that it's highly potent, highly effective, but it is also unfortunately highly toxic. We have about a 55% [rate of] grade 3/4 adverse events with that combination,” he explained. “Again, as we are looking for these checkpoints. There are several that are being studied. One of them is LAG-3; what we know about LAG-3 is that that is also co-expressed with PD-1 quite regularly on exhausted antigen specific exhausted T cells.”

“In preclinical models when you block PD-1 and you blocked LAG-3 with it that had shown quite a bit of synergy,” Tawbi continued. “The idea of being able to combine those in patients to improve their outcomes has been in study now for several years… there were definite durable response rates in patients that had already progressed on prior PD-1 or PD-1 and CTLA-4.”

“Based on that safety and clinical activity, RELATIVITY-047 was designed to study the same combination, but this time in patients with previously untreated metastatic melanoma: patients [who] are treatment naïve that have not experienced treatment with anti–PD-1 before.”

Reference

1. Tawbi HA, Schadendorf D, Lipson EJ, et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med. 2022;386(1):24-34. doi: 10.1056/NEJMoa2109970