SPOTLIGHT Results Show Promise for the Future of Gastric/GEJ Cancer Treatment

At the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, the results of the phase III SPOTLIGHT trial were presented, showing that the addition of zolbetuximab, an investigational first-in-class Claudin (CLDN) 18.2-targeted monoclonal antibody, to modified FOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) increased progression-free survival (PFS) in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinomas and CLDN 18.2 expression.

In this exclusive MedPage Today video, Paul E. Oberstein, MD, of NYU Langone’s Perlmutter Cancer Center in New York City, discusses the SPOTLIGHT trial, and how these results might help kick-start an exciting future in the treatment of gastric cancers.

Following is a transcript of his remarks:

This year at GI ASCO in 2023, there was some really exciting data presented about gastric cancer. As I think many of us felt, it was the beginning of a wave of treatment. So we’re very optimistic that it will not only lead to good results in the immediate future, but many options coming down the road.

And that’s partly because we saw a very positive study about a new target called Claudin 18.2, which is a specific target, which is very common in gastric cancer and some other GI cancers. And the clinical trial showed that an antibody against that target in combination with chemo was able to show significant benefit in survival and other outcomes in a selected patient population that had high expression of that target. So this is exciting on its own. It’s also exciting for the future because there are many other ways to look at this target.

There are other drugs in development, there are antibody-drug conjugates. There’s other combinations. And, as I said, this also applies to a larger spectrum of gastric and other GI cancer patients. So we’re optimistic that there’ll be new developments that will advance this beyond just the setting we saw in this meeting, into other indications and other drugs.

So, the SPOTLIGHT trial was a phase III trial, which looked at patients with high expression of Claudin 18.2 in their tumor, and they were randomized to get chemo plus an experimental agent called zolbetuximab, which targets Claudin 18.2 versus chemo alone plus placebo, and showed benefit with the experimental arm.

There are further steps in this development program looking at this in other settings, but this was a trial that was sort of started before immunotherapy was widely adopted.

One of the big questions is, does this combine with immunotherapy? Does it have a different patient population? So some people get immunotherapy, some will get this targeted therapy. I think that’s a question that ongoing trials both with zolbetuximab and with other Claudin 18.2-targeting agents are going to answer, which is, how early can you use this? In which population? How much Claudin do you need for it to make sense? And what’s the combination that will make the most sense?