TIL Therapy Demonstrates Durable Efficacy and Manageable Safety in Heavily Pretreated Advanced Melanoma

Iovance Biotherapeutics’ lifileucel (LN-144), an investigational autologous tumor infiltrating lymphocyte (TIL) therapy, showed encouraging efficacy and a manageable safety profile in pooled data from 2 cohorts of patients with heavily pretreated advanced melanoma in the phase 2 C-144-01 (NCT02360579) clinical trial which were presented at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting, November 8-12, 2022, in Boston, Massachusetts.

The data included an independent review committee (IRC)-assessed objective response rate (ORR) of 31.4%, with 9 complete responses and 39 partial responses. At a median followup of 36.5 months, the median duration of response (DOR) was not reached, and 41.7% of responding patients had a DOR of 24 months or more. The median overall survival (OS) was 13.9 months and the 12-month OS rate was 54% (95% CI: 45.6%, 61.6%).

“[Responses to lifileucel were observed] across all subgroups analyzed, including BRAF mutational status and PDL-1 tumor proportion score,” Amod A. Sarnaik, MD, FACS, Moffitt Cancer Center, said in his presentation of the data. “Some of target lesion diameters above the median and elevated lactate dehydrogenase (LDH), both known negative prognostic factors, were each independently correlated with a lower response. Patients with some of target lesion diameters below the median and a normal LDH had a greater likelihood of response than those with either or both of these adverse factors being higher. This suggests that the earlier use of lifileucel in disease progression may provide a greater benefit for patients.”

In terms of safety, all patients experienced at least 1 treatment-emergent adverse event (TEAE) and 94.9% of patients experiencedat least a single grade 3 or grade 4 TEAE. The most common non-hematologic AEs were chills, pyrexia, febrile neutropenia, hypophosphatemia, hypotension, fatigue, and diarrhea. Most TEAEs were transient and consistent with expectations regarding lymphodepletion and IL-2 dosing. Within the first 2 weeks following lifileucel administration, the incidence of TEAEs reduced rapidly, which Sarnaik highlighted as a benefit of the treatment not requiring multiple cycles.

The multicenter study consists of 4 cohorts and is the largest ever study of a TIL therapy in advanced melanoma for patients previously treated with immune checkpoint inhibitors. The study recruited patients with unresectable metastatic melanoma treated with at least 1 prior systemic therapy, including a PD-1-blocking antibody, and for patients with a BRAF v600 mutation, a BRAF inhibitor ± MEK inhibitor. The data included in Sarnaik’s presentation came from patients in cohort 2 (n=66) and cohort 4 (n=87) and have a cutoff date of July 15, 2022. Participants in these cohorts are required to be 18 years of age or older, have at least 1 tumor lesion resectable for TIL manufacturing and at least 1 tumor lesion for response assessment, and to have an Eastern Cooperative Oncology Group performance status of 0 to 1. The actual ages in the combined group of patients in cohorts 2 and 4 (n=153) ranged from 20 to 79 (median, 56). There were 83 male patients and 70 female patients included. There was no eligibility limit on the number of prior therapies received, and Sarnaik emphasized that the group was heavily pre-treated, with the patients’ having received a median of 3 prior lines of therapy (range, 1 to 9). 

“While 39 of the 48 responders achieved a response at the time of the very first disease assessment at 6 weeks, many responses deepened over time, with some late best response conversions,” Sarnaik said during the presentation. “For example, 7 who were initially a partial response improved to a complete response, and 10 improved from stable disease to partial response. Notably, there were 2 conversions to complete response that occurred more than 2 years after lifileucel infusion without any additional treatment.”

REFERENCE

Sarnaik A.789 Lifileucel TIL cell monotherapy in patients with advanced melanoma after progression on immune checkpoint inhibitors (ICI) and targeted therapy: Pooled analysis of consecutive cohorts (C-144-01 study). Presented at: Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting November 8-12, 2022; Boston, Massachusetts.