A phase II, multicenter study to assess the efficacy and safety of autologous tumor infiltrating lymphocytes (LN-144) for treatment of patients with metastatic melanoma

Adoptive cell therapy (ACT) utilizing tumor-infiltrating lymphocytes (TIL) has been employed for years in hundreds of patients with metastatic melanoma and other solid tumors, demonstrating durable and complete responses, even in heavily pretreated patients. Despite the approvals of checkpoint-directed therapies, metastatic melanoma remains an unmet need due to progression subsequent to administration of checkpoints, as well as due to intolerance. The C-144-01 study will enroll metastatic melanoma patients who progressed on anti-PD-1 and BRAF inhibitors if BRAF mutation positive. This phase II trial utilizes a central GMP facility for the manufacture of LN-144 in either a non-cryopreserved generation-1 (Gen-1), or cryopreserved generation-2 (Gen-2) investigational TIL infusion product. The Gen-2 manufacturing process reduces the time required for manufacture of TIL product to 22 days. The process development of cryopreservation for the final LN-144 infusion product incorporates dramatic improvements in the flexibility of scheduling, distribution and delivery required for commercial use. C-144-01 (NCT02360579) is a global phase 2 multicenter, open-label study evaluating the efficacy and safety of autologous TIL (LN-144) therapy for the treatment of patients with advanced metastatic melanoma. The study consists of three treatment cohorts: 30 patients in Cohort 1 will receive a single dose of Gen-1, non-cryopreserved LN-144; 30 patients in Cohort 2 will receive a single dose of Gen-2, cryopreserved LN-144; and up to 10 eligible patients from either Cohort 1 or Cohort 2 may enter a third cohort (Cohort 3) for re-treatment with a second dose of LN-144. The investigational LN-144 TIL infusion product for all cohorts is prepared at the central GMP facility using lymphocytes that are extracted from a surgically-resected sample of patient tumor. LN-144 infusion is preceded by a non-myeloablative lymphodepletion regimen of cyclophosphamide and fludarabine and followed by IL-2 for up to 6 doses. Patients ≥ 18 years of age must have progressive, unresectable metastatic melanoma (Stage IIIc or Stage IV) following ≥1 line of prior systemic therapy including immune checkpoint inhibitors and BRAF-targeted therapy (if BRAF mutation-positive). A minimum of 2 tumor lesions are required: 1 for resection and TIL manufacture and 1 for assessment of response by RECIST 1.1 criteria. Other major eligibility criteria include: adequate bone marrow, cardiac, liver, pulmonary, and renal function; ECOG PS of 0 or 1. Efficacy is being assessed as a function of ORR, CR rate, DOR, DCR, and PFS per RECIST 1.1 and OS. Assessment of safety data will be descriptive and based on the summarization of TEAEs, SAEs, AEs leading to discontinuation from treatment and the study, vital signs, physical examinations, and clinical laboratory tests. Citation Format: Amod Sarnaik, Brendan Curti, Diwakar Davar, Omid Hamid, Jose Lutzky, Melissa Wilson, Harriet Kluger, Jason Chesney, Kevin Kim, Giao Phan, Sajeve Thomas, Eric Whitman, Bente Larsen, Sam Suzuki, Nancy Samberg, Igor Gorbatchevsky, Maria Fardis, John M. Kirkwood. A phase II, multicenter study to assess the efficacy and safety of autologous tumor infiltrating lymphocytes (LN-144) for treatment of patients with metastatic melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT169.