Anti-LAG-3, Pembrolizumab Doublet Continues to Impress in Metastatic NSCLC

At the recent American Society of Clinical Oncology (ASCO) annual meeting, updated results of a phase II trial showed that the lymphocyte activation gene (LAG)-3 inhibitor eftilagimod alpha in combination with pembrolizumab (Keytruda) is safe and has antitumor activity as first-line therapy for metastatic non-small cell lung cancer, regardless of PD-L1 status.

In this exclusive MedPage Today video, Benjamin Creelan, MD, of the Moffitt Cancer Center in Tampa, Florida, discusses the trial results.

Following is a transcript of his remarks:

Here at ASCO, I’m excited to be really back on site at ASCO after a 2-year hiatus. And one of the abstracts that struck me was the recently presented TACTI-002 trial, which actually was a phase II using a LAG-3 antibody. But this works differently than other LAG-3 antibodies.

This trial randomized 114 patients with metastatic stage IV lung cancer, regardless of PD-L1 status to get a combination of pembrolizumab — which we know has response rates of maybe 10% to up to 30% in this population — also receive this efti [eftilagimod], which is an antibody agonist for LAG-3.

Remember almost all the other LAG-3 antibodies we’ve seen in trials have been antibodies which inhibit LAG-3. So this actually stimulates it, in stimulating the antigen-presenting cell, which really makes sense. You’re combining an immune checkpoint inhibitor like PD-1 with an agonist like efti, and you’re seeing this increased response rate.

So the result was that 44 out of those 114 patients had objective RECIST [Response Evaluation Criteria in Solid Tumors] responses. And so that translates into a response rate of around 40% higher than we’d conventionally expect, and compared to historical controls, substantially higher.

So I think this is an interesting proof of principle, a very intriguing early phase II result. It definitely needs to be reviewed more in randomized later-stage phase III trials, but at the end of the day I think it certainly heralds promise for this approach.

This drug has been around for a long time actually. This is the product of Frédéric Triebel, who discovered LAG-3 in 1990. He’s one of the founders of this company [Immutep]. And it’s been tested in breast cancer in combination with paclitaxel. So far, nothing in phase III trials have been confirmatory in that setting.

But I would say that this is a setting that makes a lot of sense. And we know that LAG-3 is more than just an inhibitory immune checkpoint. We know that it actually does stimulate antigen-presenting cells too. So combining these two theoretically is an important thing.