WCLC 2021 | CONFIRM trial: nivolumab in relapsed malignant mesothelioma

CONFIRM is a randomized Phase III trial of nivolumab, evaluating anti-PD-1 immunotherapy in a relapsed setting. Which is a setting of unmet need, a setting in which we don’t have yet a licensed treatment. This study was a double-blind placebo-controlled study using overall survival and progression-free survival as the primary endpoints. The study met its primary endpoints, both for PFS, overall survival. It’s important to mention that because of COVID, we had to stop the study rather early, although we were very close to full recruitment. And when we did the evaluation of the number of events that we had at that point in time, or that we’re likely to have over the four coming months, we realized that we had enough power through the expected events to be able to complete the study successfully. So we stopped recruitment March of last year, and we went on to August when the IDMC, our Independent Data Monitoring Committee, recommended release of the results. Of course, they had unblinded access to those results as committees should. And on the basis of that, we were able to present early.

What’s key is that the overall survival was immature in this study result that I’ve presented at IASLC. We had a target of about 290 or so events, survival events, but what we’re presenting is 230, approximately. And so we will have some further maturation of the data. But nevertheless, based on the top level results, we saw what was a balanced population of patients with pleural and parenchymal mesothelioma. We saw superiority of nivolumab over and above placebo. Hazard ratio was 0.72, P-value was 0.018, and progression-free survival had a hazard ratio of 0.61, with a P-value of less than 0.001.

In the results that we presented, we were also able to look at really important strata. So we looked at the PD-L1 expression. The PD-L1 has been very controversial in mesothelioma. It’s been cited as a negatively prognostic factor. Of course, it’s supposed to be as it is, of course, in lung cancer a predictive factor. And so we used 22C3, which is a clone of PD-L1 antibody by the Dako, which is used in our practice and we know very widely around the world in lung cancer to estimate the tumor proportion score expression of PD-L1. And with that test, using the standard approach to measuring tumor proportion score, we did not see any impact at all, either on the control arm, which might suggest prognostic impact, or on the experimental arm to suggest a predictive effect. And this was a pretty statistically robust outcome.

We also looked at histology, and with histology we found the epithelioid subgroup, around around about 88% of patients, the hazard ratio was 0.71, significant advantage for patients with epithelioid disease. This is important because in the CheckMate 743, the benefit of that therapy, statistically when looking at subgroups, seem to be very much focused on the non-epithelioid subgroup. Mostly of course, because these patients did very, very badly with chemotherapy. So what we found here in CONFIRM is that a group of patients who do approximately the same with immunotherapy in the front-line or with chemotherapy, well, in the relapse setting, it’s a robust benefit over and above placebo. In terms of safety, we compared of course placebo with drug, and we found no signal to give us any concerns regarding toxicity. And for that reason, we’re confident this is a safe treatment to administer. So in summary, nivolumab met its primary endpoint. It’s a safe, effective treatment. I think this will provide some opportunity for certain patients who have unmet need in this setting.