Panel Discusses Implications of 5-Year Data From CheckMate 9LA

A roundtable discussion, moderated by Millie Das, MD, covered challenges, advances, and future directions for the diagnosis, treatment, and management of non-small cell lung cancer (NSCLC), as well as critical clinical trial data and updates from the 2024 American Society of Clinical Oncology Annual Meeting. Dr. Das was joined by Ticiana Leal, MD, Martin Dietrich, MD, PhD, and Kent Shih, MD.

In the fifth segment of the roundtable series, the panel discusses the 5-year follow-up results from CheckMate 9LA that were presented at the 2024 American Society of Clinical Oncology Annual Meeting, and the implications of this long-term data.

In the next segment, the panel discusses unanswered questions in NSCLC.

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Dr. Das: I’d like to talk a little bit more about the 5-year overall survival data that we have seen from CheckMate 9LA at this conference and wanted to get your impressions on the 5-year data. What do you make of this? Does this, I guess, change your impressions of the particular regimen?

Dr. Leal: We’ve now seen 5-year of CheckMate 189 [and] 407. We are seeing 9LA here at [the American Society of Clinical Oncology Annual Meeting], and we have longer term also for POSEIDON. I think that overall, the way that I interpret the data is number 1, you have some patients that really benefit from immunotherapy across all of these trials. Clearly PD-L1 as a marker for enriching for that magnitude of benefit. People with PD-L1 high expression in their tumors, clearly those are the people that are benefiting the most. We know that. I don’t think that’s any surprise as we see the 5-year data.

What we saw with the updated analysis now of the CheckMate 9LA is the 5-year overall survival in all patients of 18%. I think we were talking about how KEYNOTE-189 and 407 for all-comers 18% is kind of what we saw. And then looking at the subsets of who is benefiting less across the trials of chemoimmunotherapy, we talked about how the PD-L1 subset seems to have less benefit but still benefiting compared to chemotherapy.

And then when we look at CheckMate 9LA, I think it really is striking to see the PD-L1-negative subsets do seem to have that benefit from immunotherapy with the addition of the CTLA-4 inhibitor, and the squamous population. So, those are the 2 sort of subsets that come out as people that historically we’ve seen inferior outcomes [in] compared to the other subsets of PD-L1, middle ground and high. I think the CheckMate 9LA data, the 5-year survival, it’s really nice to see. I don’t think there were any surprises, but it also tells me that we still need to focus on those subsets. We still need to focus on how we get more benefit for people with PD-L1 negative tumors, and also the squamous population.

Dr. Das: Any other thoughts?

Dr. Dietrich: Well, I would agree. I mean if you think about how we came to develop these trials, CheckMate 227 was actually the trailblazer. And we saw in part 1B of CheckMate 227, an unexpected and pretty significant long-term positive outcome in the PD-L1-negative subset with an overall survival of about 30% at the 5-year mark. So that set a very high bar and certainly not data that we were able to fully reproduce, this maybe because of the negative impact of chemotherapy, or it may just been sort of a trial result that it was a little variable, but it certainly laid the ground that we were able to reproduce in CheckMate 9LA and POSEIDON that in the PD-L1-negative disease, we do see, across the histology types, but preferentially in the underperforming squamous subtype, an increase in long-term survival. I think those are numbers that are quite reassuring. We don’t have quite the full year, 5-year follow-up for POSEIDON. For CheckMate 9LA, it’s now very clear that we are seeing levels here that are higher than expected.

Very difficult to analyze the trial without having a PD-1 arm intrinsically. This would be nice for intrinsic comparison, but I think in historical comparisons, I think we don’t see any benefit with PD-1 in the long term set up in the PD-L1 negative population, and a very marginal benefit in the non-squamous population and CheckMate, and sorry, in KEYNOTE-407 and 189 respectively.

I think this is a stronghold where we underutilize CTLA-4 inhibition. I think this is proven in 3 trials, 2 agents where this should be utilized. And then again, case by case, I think high-risk distribution CTLA-4 and circulatory lymphocytes, may be the reason why we’re seeing better brain metastatic coverage for these patients. We really have an egalitarian effect between brain [metastases] and no brain [metastases] in CheckMate 9LA. It’s very nice to see. And obviously the sensitization of squamous cell is going to be very, very useful.

I’m very happy that we have these regimens available. The [National Comprehensive Cancer Network] guidelines support ipilimumab and nivolumab as a chemotherapy-free option for the PD-L1 zeroes, and I think that’s the signature utility for the drug. I think we need to look at the toxicities, discuss it with the patient, but in a patient with a negative and unfavorable biomarker setup, it is really one of the immunosensitizing opportunities.

Dr. Shih: When I look at [immuno-oncology] versus [chemotherapy]-type trials, one of the first things I look at in an OS curve is: do they split early on? And so, for 227 they do. Maybe in EMPOWER-Lung 1 they don’t. But that informs me, as a practitioner, that there’s still a patient population, unfortunately, that needs chemo. And so, we’re not there yet. Maybe in the era of [bispecific T-cell engagers] and [antibody-drug conjugates], cellular therapies for solid tumors, we can move past that. But I think we are still in that era where there are patients that unfortunately still need chemotherapy.

Dr. Das: Yeah, and I think we have these caveats of looking at these subgroup analyses doing these cross-trial comparisons, which we’re really not supposed to be doing, but that’s all we have to guide us.

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View the first segment of this roundtable series here.

View the second segment of this roundtable series here.

View the third segment of this roundtable series here.

View the fourth segment of this roundtable series here.