Long-Term Success With Anti–LAG-3/Anti–PD-1 Combo in Metastatic Melanoma

Meredith McKean, MD, MPH

A recent long-term follow-up of a phase 1 study (NCT03005782) found that the combination of fianlimab, an anti–LAG-3 agent, and cemiplimab (Libtayo), an anti–PD-1 agent, showed promising efficacy and safety in patients with advanced melanoma.

The primary end point of the trial was overall response rate (ORR) as assessed by blinded independent central review (BICR).

The study found that the combination therapy achieved a BICR-assessed ORR of 57% (95% CI, 47%-67%) with a median progression-free survival of 24 months (range, 12-not evaluable [NE]). The ORR was consistent across different subgroups, including those with low PD-L1 or LAG-3 expression. The median duration of response was not reached (95% CI, 23-NE), with a significant proportion of patients maintaining responses for at least 1 year, and some for 2 years. Further, the rate of complete responses increased over time, suggesting the potential for long-term benefits. Immune-mediated adverse events were similar to those seen with PD-1 monotherapy with a manageable safety profile.

The results of this study demonstrated that fianlimab plus cemiplimab is a promising treatment option for patients with advanced melanoma.

In an interview with Targeted Oncology^TM, Meredith McKean, MD, MPH, director of melanoma and skin cancer research at Sarah Cannon Research Institute, discussed the findings and implications of these data.

Targeted Oncology: What were the goals of this longer-term follow-up?

McKean: The goals of this additional follow-up were to be able to have additional follow-up on the primary end point of objective response rates and then be able to look at some of the additional secondary end points of progression-free survival and duration of response. We were trying to build on some of that initial data looking for the durability of those initial responses for patients.

Could you give some background on the agents being evaluated here?

This study evaluated fianlimab, which is an anti–LAG-3 monoclonal antibody, with cemiplimab, which is an anti–PD-1 monoclonal antibody. This was an expansion study from the initial dose escalation of this combination of the anti–LAG-3 and anti–PD-1 combination. This study initially evolved at a time where anti–PD-1monotherapy in the frontline setting was the standard of care.

Could you discuss how these long-term follow up findings compare with the initial findings?

The initial analysis was presented at [the American Society of Clinical Oncology Annual Meeting] in 2023. There were 3 different cohorts that were evaluated: the initial frontline cohort in the metastatic melanoma setting, patients that were anti–PD-1-naive; a confirmatory cohort of additional patients; and then a third cohort of patients that had previously received either neoadjuvant or adjuvant anti–PD-1 [therapy]. In the initial results presented last year, we saw response rates between 56% to 63%.

With this additional follow-up, with a median follow up of 23 months with the evaluation of the blinded independent central review, we saw a relatively preserved objective response rate of 57%, and we saw ongoing durability of those initial responses that patients had. Additionally, the complete response rate was 25%, and so we saw that deepening with time, which is exciting for our patients.

Did you identify any new safety signals?

Overall, from a safety standpoint, it was felt to be a very well-tolerated regimen, which is important. Ultimately, the goal is to be able to have efficacious and safe regimens. There were no new safety signals seen with the longer-term follow-up.

Based on these findings, what would you consider to be the major implications for physicians?

I think there's certainly a lot of excitement with this regimen. We have continued to see a doubling of the objective response rate seen with just anti–PD-1 [therapy] and seen a common objective response rate more similar to ipilimumab [Yervoy] and nivolumab [Opdivo] in the frontline setting but [with] a much better tolerated safety profile. There are now additional ongoing studies in the adjuvant and frontline metastatic setting, so I think certainly a lot of excitement there.

In this patient population, what would you consider to be some of the unmet needs that still exist?

Unfortunately, we know, historically, that nearly 50% of patients are still succumbing to metastatic melanoma, and so I think we continue to need other treatments for patients in the metastatic setting, in addition to moving these combination approaches into the earlier setting, so in the adjuvant and neoadjuvant settings, to be able to try to prevent patients from developing metastatic disease.

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: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract 1097P.