Fianlimab Plus Cemiplimab Produces Durable Responses in Advanced Melanoma


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Omid Hamid, MD, discusses the key efficacy and safety findings for the combination of fianlimab plus cemiplimab in patients with advanced melanoma.

Omid Hamid, MD

Omid Hamid, MD

The efficacy displayed by treatment with the combination of the LAG-3 inhibitor fianlimab (REGN3767) and the PD-1 inhibitor cemiplimab (Libtayo) in a phase 1 trial (NCT03005782) in patients with advanced melanoma has led to the initiation of further studies, and this combination could potentially serve as the backbone for triplet and quadruplet therapy in other future investigations, according to Omid Hamid, MD.

Data from the phase 1 study presented by Hamid at the 2023 ASCO Annual Meeting showed that at a follow-up of 12.6 months (interquartile range, 8.6-19), a combined population of 3 cohorts of patients with advanced melanoma who received the combination (N = 98) achieved an objective response rate (ORR) of 61% (95% CI, 51%-71%) with a complete response rate of 12%. The median duration of response (DOR) was not yet reached (95% CI, 23–not estimable [NE]) and the disease control rate was 78% (95% CI, 68%-85%).

Additionally, the estimated median progression-free survival (PFS) was 15 months (95% CI, 9-NE) with an estimated 12-month event-free probability of 52% (95% CI, 41%-62%). Clinical activity was observed in poor prognosis subgroups, such as patients with liver metastases (n = 21), baseline lactate dehydrogenase (LDH) greater than the upper limit of normal (ULN; n = 32), or an M1c stage and LDH greater than ULN (n = 17), who experienced ORRs of 43% (95% CI, 22%-66%), 53% (95% CI, 35%-71%), and 35% (95% CI, 14%-62%), respectively.

Regarding safety, any-grade treatment-emergent adverse effects (TEAEs) occurred in 94% of patients, including 44% that were grade 3 or higher. Any-grade treatment-related adverse effects were reported in 79% of patients, with 22% being grade 3 or higher. Commonly occurring any-grade treatment-emergent immune-related adverse effects included rash (20%), pruritis (16%), and diarrhea (15%). Sixteen patients discontinued treatment with the combination due to a TEAE.

“Where does this take us in the field of advanced melanoma? We have another combination [here] that’s being looked at now in a randomized phase 3 fashion in the advanced setting [NCT05352672] and in the adjuvant setting [NCT05608291],” Hamid said.

In an interview with OncLive®, Hamid, the chief of Translational Research and Immunotherapy, director of Melanoma Therapeutics, and a medical oncologist at the Angeles Clinic and Research Institute, a Cedars-Sinai affiliate, in Los Angeles, California, further discussed the key efficacy and safety findings for the combination of fianlimab plus cemiplimab in patients with advanced melanoma.

OncLive: What led to the initiation of the phase 1 trial evaluating fianlimab plus cemiplimab in patients with advanced melanoma?

Hamid: Fianlimab is an anti­–LAG-3 antibody, and cemiplimab is a well-known anti–PD-1 antibody. We know that the combination of LAG-3 inhibition and PD-1 inhibition has led to improvements in response rates and PFS in advanced melanoma. Initial data [from the phase 1 trial] were presented at the 2022 ESMO Congress, showing a 64% ORR [in the PD-1–naïve population].

This is an update on the PD-1­–naïve population in the adjuvant setting, and it is the first time we have presented data on our patients who have [received prior] therapy, including anti–PD-1 antibodies in the adjuvant/neoadjuvant setting, who then progressed or relapsed at 6 months or more and were treated with this regimen.

Fianlimab was given at [a dose of] 1600 mg intravenously [IV] every 3 weeks along with cemiplimab at 350 mg IV every 3 weeks. This is important because this is the highest dose of a LAG-3 antibody given, and it [was given at] an increased frequency when compared with other regimens.

What were the key findings from the trial presented at the 2023 ASCO Annual Meeting?

We saw a continued benefit and a continued high ORR of 63% [in the PD-1–naïve cohorts]. We saw responses even in poor prognostic cohorts of patients, [including those with] liver metastases, high LDH, [and] M1c [disease]. We also saw response regardless of PD-L1 or LAG-3 staining of the cells.

This was a very well tolerated regimen, even in patients who had seen PD-1 [agents] in the adjuvant setting. We didn’t see any new safety signals.

The toxicities were similar to [those of] single-agent anti–PD-1 therapy, except for an increased incidence of adrenal insufficiency. Those were mostly grade 1 or 2 and were all resolved with the initiation of steroids.

Not only was [this combination] well tolerated and not only did it have a response rate of 63%, but it had a [median] DOR that had not been reached. In the [combined] cohorts, we saw a PFS of 15 months, which is a very interesting and high PFS.

What are some of the other possible future directions for researching this combination?

This is a combination that is now being looked at in triplets in the adjuvant, neoadjuvant, and other settings. We’re moving the field forward in checkpoint inhibition in advanced melanoma.

The one caveat is that all of these trials start in melanoma and then transition to other solid tumors. The ability to utilize this combination to garner improvements in ORR, PFS, and other end points in other solid tumors is novel. I look forward to that data at future meetings.

What is a main message for colleagues regarding this updated data?

We have a combination in advanced melanoma that has a high ORR, high durability, and an excellent PFS. We look forward to utilizing [this combination] in future trials. There are phase 3 trials looking to cement the benefit here. I encourage my colleagues who have patients to refer them for clinical trials, and I look forward to utilizing this combination [as part of] triplets and quadruplets in future studies.

Disclosures: This study was sponsored by Regeneron Pharmaceuticals, Inc.


Hamid O, Lewis KD, Weise AM, et al. Significant durable response with fianlimab (anti-LAG-3) and cemiplimab (anti-PD-1) in advanced melanoma: post adjuvant PD-1 analysis. J Clin Oncol. 2023;41(suppl 16):9501. doi:10.1200/JCO.2023.41.16_suppl.9501

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