Dr Hamid on Addressing Unmet Needs in Relapsed Melanoma With Lifileucel

Omid Hamid, MD, professor, medicine, Cedars-Sinai; director, Clinical Research and Immunotherapy, director, Cutaneous Oncology and Melanoma, The Angeles Clinic and Research Institute, discusses how the tumor-infiltrating lymphocyte (TIL) lifileucel (Amtagvi) may address historical unmet needs in relapsed melanoma.

On February 16, 2024, the FDA approved lifileucel for the treatment of patients with unresectable or metastatic melanoma who were previously treated with a PD-1 inhibitor as well as a BRAF inhibitor with or without a MEK inhibitor if they had BRAF V600–mutated disease. This regulatory decision, as well as additional research with lifileucel in melanoma, has addressed some needs for patients in this population, Hamid says. This agent is effective in patients who have never responded to or progressed on checkpoint inhibitor therapy, Hamid explains.

In the pivotal phase 2 C-144-01 trial (NCT02360579), lifileucel elicited a 31.5% objective response rate (ORR) and durable responses in heavily pretreated patients. In this trial, patients had received a mean of 3.3 prior lines of therapy. All patients had progressed on PD-1/PD-L1 inhibitors, 80% of patients had progressed on CTLA-4 inhibitors, and 23% of patients had progressed on BRAF/MEK inhibitors.

Furthermore, checkpoint inhibitors and TILs have been shown to be effective in difficult-to-treat melanoma subtypes, such as mucosal melanoma, Hamid emphasizes. In the mucosal melanoma cohort of the C-144-01 trial (n = 12), the ORR was 50.0% (95% CI, 21.1%-78.9%), and the median duration of response was not yet reached (NR; 95% CI, 12.5%-NR). These findings were presented at the 2023 ESMO Congress. Lifileucel was shown to be effective in this subset of patients, who have a low tumor mutational burden compared with patients with cutaneous melanoma, and thus were not expected to respond to checkpoint inhibitors, Hamid notes. Moreover, small studies have shown efficacy with TILs other than lifileucel in ocular melanoma, Hamid concludes.