Safety and efficacy of lifileucel (LN-144), an autologous, tumor infiltrating lymphocyte cell therapy in combination with pembrolizumab for immune checkpoint inhibitor naïve patients with advanced melanoma.
Authors: Thomas Sajeve Samuel , In Gino Kim , Doger Bernard , Haefliger Simon , Martin-Liberal Juan , Goldberg Zelanna , Cacovean Alex , Fiaz Rana , Chen Guang , Jagasia Madan H. , Graf Finckenstein Friedrich , Fardis Maria , Jimeno Antonio 
Published: June 2021

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Background: Tumor infiltrating lymphocyte (TIL) cell therapy has demonstrated safety and efficacy in advanced melanoma, both in the pre-immune checkpoint inhibitor (ICI) setting (Goff, JCO 2016) and in patients who have failed anti-PD-1/PD-L1 therapy (Sarnaik, 2020). Combination of TIL and pembrolizumab (pembro) in ICI-naïve patients has demonstrated encouraging efficacy data with acceptable safety in head and neck squamous cell carcinoma (Jimeno, 2020). To improve treatment options in early lines, we explore a combination of LN-144 and pembro in patients with ICI-naïve advanced melanoma. Methods: IOV-COM-202 is a Phase 2 multicenter, multi-cohort, open-label study evaluating TIL cell therapy in multiple settings and indications. We report on Cohort 1A enrolling ICI-naïve advanced melanoma (unresectable or metastatic) patients for treatment with a combination of LN-144 and pembro. Key eligibility criteria include ≤ 3 lines of prior therapy, ECOG < 2, one resectable lesion for lifileucel manufacturing, and ≥ 1 measurable lesion for response assessment. Primary endpoints are objective response rate (ORR) per RECIST 1.1 and safety as measured by incidence of Grade ≥3 treatment-emergent adverse events (TEAE). LN-144 is generated at centralized GMP facilities in a 22-day process. A nonmyeloablative lymphodepletion (NMA-LD) using cyclophosphamide and fludarabine is administered preceding a single LN-144 infusion, followed by < 6 doses of IL-2 (600,000 IU/kg). Pembro is administered after tumor harvest but prior to NMA-LD and continues after lifileucel per label. Results: Seven patients have received lifileucel in combination with pembro as of data extraction date (Feb 14, 2021). Five of the 7 treated patients were treatment-naïve, 1 patient had prior BRAFi + MEKi and 1 had received prior chemotherapy; 71% had liver/brain lesions, 43% had LDH > ULN. Mean SOD for the target lesions was 111 mm, with 86% of patients with > 3 target lesions, representing advanced disease at baseline for this patient group. The TEAE profile was consistent with the underlying disease and known AE profiles of pembro, NMA-LD and IL-2. Six patients had a confirmed objective response with an ORR of 86% (1 CR, 5 PR) and 1 best response of SD. Three of the responding patients have remained off pembro due to pembro related AEs for 3, 4 and 13 months (mos), yet maintaining response. All responding patients remain in response with the longest duration of response being 16.8 mos. Conclusions: Lifileucel can be safely combined with pembro in patients with ICI-naïve advanced melanoma. The ORR of 86% is encouraging when compared to pembro alone in a similar patient population, especially considering the disease burden at baseline and persistence of responses in patients off therapy. Enrollment is ongoing and updated data to be presented. Clinical trial information: NCT03645928.