Expert Explains Significance of LAG-3 Inhibition in Novel Immunotherapies for Melanoma


LAG-3 represents a potentially relevant immune checkpoint pathway in melanoma treatment.

The discovery of LAG-3 inhibition may represent the first checkpoint inhibitor in over a decade, explained 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, discussed why the results of the RELATIVITY-047 trial (NCT03470922) are particularly exciting for oncologists working with immunotherapies. Tawbi is lead study author of RELATIVITY-047, which was published in the New England Journal of Medicine.

The trial findings revealed that a novel regimen of immune checkpoint inhibitors, relatlimab and nivolumab (Opdivo), yielded encouraging responses among patients with untreated, advanced melanoma, and did not exhibit any new safety signals. 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. As you know, the immune checkpoint inhibitors have revolutionized cancer in the last decade.”

“I really do want to highlight the fact that we're very excited that this is the third checkpoint inhibitor after PD-1 and CTLA-4 to show clinical activity,” he shared with Oncology Nursing News®. “It has been about a 10-year wait to find the third checkpoint inhibitor, and now we have a new agent to consider combining in different patient populations.”

“I would also like to highlight the fact that participation in clinical trial has been a critical component to make this happen,” added Tawbi. “It was a very difficult study to run during the pandemic, as a good part of it happened during the pandemic. I'm very grateful for the patients who participated. [In light of] all of the challenges that were happening, we would just like to commend them for that, and make it another call to action for all patients to consider enrollment in clinical trials, because that is how we bring progress. That's how we will have, hopefully, a new agent in hand to treat all patients

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