Fianlimab Plus Cemiplimab Shows Deep, Durable Responses in Melanoma: Dr Meredith McKean

Meredith McKean, MD, MPH, board-certified medical oncologist and director of melanoma and skin cancer research for Sarah Cannon Research Institute at Tennessee Oncology, discussed long-term follow-up results assessing fianlimab plus cemiplimab in advanced melanoma.

Transcript

What were the main findings among patients with advanced melanoma receiving fianlimab plus cemiplimab?

The data presented at ESMO 2024 [European Society for Medical Oncology] was additional follow-up for patients treated on expansion cohorts in the frontline metastatic melanoma or locally advanced melanoma setting. And what was presented demonstrated deepening responses and persistent responses in the patients who were initially treated on the study.

What do these additional long-term follow-up results add to past data on the combination regimen?

The prior data that were presented at ASCO 2023 and now updated at ESMO 2024, what we saw was a relatively preserved objective response rate now with a blinded independent central review. We had an objective response rate of 57% at that median follow-up of 23 months, and we continue to need additional follow up because we've not yet reached the median PFS [progression-free survival] or OS [overall survival].

What this demonstrates is that not only is this an efficacious regimen, but we also saw no new safety signal, which is ideal for patients to have an effective regimen that's well tolerated.

How does treatment with fianlimab plus cemiplimab address the mechanisms of melanoma?

We've seen success with targeting anti–PD-1 and anti-CTLA4 in the past. LAG-3 is another immune checkpoint, and so the idea is that fianlimab is a monoclonal antibody targeting LAG-3 with a silent Fc domain. The idea was, well, can we combine this LAG-3 monoclonal antibody with an anti–PD-1 and see if we can achieve better efficacy while maintaining safety?

Can you discuss the high-risk subgroups included in the study and how these patients responded to the regimen?

There were a large number of patients who had some of these poor prognostic features that were enrolled. In melanoma, those are patients with elevated LDH [lactate dehydrogenase]; with visceral metastases, such as liver metastases, and also patients that have previously received neoadjuvant or adjuvant anti–PD-1. And what we've seen is that the objective response rates were relatively preserved in these patient subgroups.

I'll mention that presenting on patients and enrolling patients who have received prior anti–PD-1 in the neoadjuvant or adjuvant setting has not been demonstrated in a lot of studies, and so that was really novel data to show.

How do the efficacy and safety of fianlimab plus cemiplimab compare with current standard therapies for advanced melanoma?

I think the excitement here is that, with an objective response rate around 57%, this is very similar to what we've seen in randomized trials with ipilimumab and nivolumab, but with a much better safety profile. Now these are certainly early data, not a randomized study, but I think certainly leads to a lot of excitement. It's very clear that the objective response rates are much better than what we've seen with anti–PD-1 monotherapy. And so now this combination is being explored in the frontline setting and also in the adjuvant setting to see, can we provide a regimen with more efficacy that's really well tolerated for these patients?

Reference

McKean M, Weise AM, Papadopoulos KP, et al. Long-term follow-up of advanced melanoma (unresectable/metastatic - aMel) patients (pts) treated with fianlimab (FIAN) + cemiplimab (CEMI): Results from blinded independent central review (BICR) efficacy assessment. Presented at: European Society of Medical Oncology Congress 2024; September 13-17, 2024; Barcelona, Spain. Poster 1097P.