Omid Hamid, MD, director, Melanoma Program, Cedars-Sinai Medical Center, chief, Translational Research and Immunotherapy, director, Melanoma Therapeutics, Phase I Immuno-Oncology Program, The Angeles Clinic and Research Institute, discusses the investigation of the LAG-3 inhibitor fianlimab (REGN3767) in combination with cemiplimab-rwlc (Libtayo) in patients with advanced melanoma who were naïve to anti–PD-1 agents in the advanced setting.

Data from a phase 1 trial (NCT03005782) presented at the 2023 ASCO Annual Meeting showed that across 3 cohorts of patients, including 1 that included those who received anti–PD-1 treatment in the neoadjuvant or adjuvant setting, the combination elicited an overall response rate of 61% (95% CI, 51%-71%). Notably, responses were observed across key subgroups, including patients with poor prognosis, such as those with high lactate dehydrogenase or liver/visceral metastases, Hamid says.

The median duration of response was not reached among all patients, and the estimated median progression-free survival was 15 months (95% CI, 9–not estimable).

Safety data showed the regimen was well tolerated, even in patients who received anti–PD-1 therapy in the adjuvant setting, and no new safety signals were observed, Hamid explains. Although the toxicities were similar to what would be expected from treatment with single-agent anti–PD-1 therapy, there was an increased incidence of adrenal insufficiency; however, these adverse effects were generally grade 1 or 2, and these events were resolved with steroids, Hamid notes.

Further investigation of fianlimab plus cemiplimab is currently ongoing for patients with melanoma, including those in the advanced setting in a phase 3 trial (NCT05352672), and in the adjuvant setting in another phase 3 study (NCT05608291). The combination is also being explored in triplets and in other settings, Hamid concludes.

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Omid Hamid, MD, discusses the investigation of the LAG-3 inhibitor fianlimab in combination with cemiplimab in patients with advanced melanoma who were naïve to anti–PD-1 agents in the advanced setting.


Dr Hamid on the Investigation of Fianlimab With Cemiplimab in Advanced Melanoma

Omid Hamid, MD, director of the Melanoma Center and Phase I Immuno-Oncology Program at The Angeles Clinic and Research Institute, discusses the utility of tumor mutational burden (TMB) as a biomarker for response to immunotherapy in patients with melanoma.

TMB is not just for melanoma, says Hamid. By examining TMB, investigators have done a significant job in helping to understand which patients will respond best to immunotherapy across a multitude of tumor types. Investigators have looked at high TMBs to determine response to immunotherapy within the context of CTLA-4 and PD-1 inhibitors; several papers have analyzed this. For example, an article published in the 

by Alexandra Snyder, MD, head of Translational Oncology at Merck, looked at TMB for CTLA-4 response, says Hamid.

It is known that TMB for PD-1 response is important, which can be seen by the FDA approval of pembrolizumab (Keytruda) for patients high TMB; this marker is an indicator of a patient who is going to have a higher response rate to immunotherapy, concludes Hamid.

Omid Hamid, MD, discusses the utility of tumor mutational burden as a biomarker for response to immunotherapy in patients with melanoma.

Dr. Hamid on TMB as a Biomarker for Immunotherapy Response in Melanoma

, chief, Translational Research and Immunotherapy, director, Melanoma Therapeutics, 

The Angeles Clinic and Research Institute

, discusses melanoma as a therapeutic driver for other tumor types during the 13th Annual International Symposium on Melanoma and Other Cutaneous Malignancies

The background of everything is that the data that have come out of melanoma is relatable to multiple other solid tumors. For example, BRAF and MEK inhibitors have efficacy and utility in other solid tumors, Hamid explains. There have been data presented on lung cancer and colorectal cancer. Hamid raises the question: what if researchers combine BRAF and MEK inhibitors in these cancers, as has been done in melanoma, as well?

Immunotherapy itself in combination has utility in melanoma and is now moving into other tumor types, such as bladder and lung cancer. The next step, he adds, is taking these data and increasing efficacy for patients with every solid tumor. This is becoming more evident in clinical practice, where melanoma is becoming the therapeutic driver for other solid tumor types. From observation, Hamid notes that patients are now asking how physicians will treat their immunotherapy responsive or immunotherapy non-responsive tumors.

Omid A. Hamid, MD, chief, Translational Research and Immunotherapy, director, Melanoma Therapeutics, The Angeles Clinic and Research Institute, discusses melanoma as a therapeutic driver for other tumor types during the 13th Annual 13th Annual International Symposium on Melanoma and Other Cutaneous Malignancies® in Sunny Isles Beach, Florida.

Dr. Hamid on Melanoma as a Therapeutic Driver for Other Cancers

Omid A. Hamid, MD, chief, Translational Research and Immunotherapy, director, Melanoma Therapeutics, The Angeles Clinic and Research Institute, discusses how to accurately select patients who are likely to have durable and long responses with single-agent immunotherapy versus combination treatment.

Specifically, Hamid explains, the question should be, "Who will respond best to single-agent immunotherapy or to one of the many combinations, whether they be in clinical trials or are approved by the FDA?" Steps to evaluate this will be with newer assays beyond PD-L1 staining, mutational load status, CD8-positive T-cells in the tumor biopsy specimen, and exhausted T-cell phenotypes.

These are all approaches that have been explored and presented, and will be reviewed in the near future.  

Omid A. Hamid, MD

Articles

Dr Hamid on the Investigation of Fianlimab With Cemiplimab in Advanced Melanoma

Dr. Hamid on TMB as a Biomarker for Immunotherapy Response in Melanoma

Dr. Hamid on Melanoma as a Therapeutic Driver for Other Cancers

Dr. Hamid on Patient Selection for Immunotherapy Regimens in Melanoma