DELTA-1: A global, multicenter, phase 2 study of ITIL-168, an unrestricted autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in adult patients with advanced cutaneous melanoma.

Abstract

TPS9594 Background: Patients (pts) with advanced (unresectable or metastatic) cutaneous melanoma and persistent disease after checkpoint inhibitor therapy have poor outcomes and limited treatment options, highlighting a significant unmet medical need (Schadendorf D et al. Lancet. 2018;392:971-984). Investigational autologous TIL cell therapies have shown promise in this population, partly attributable to their intrinsic and patient-specific antitumor activity (Borch TH et al. J Immunother Cancer. 2020;8:e000668). Made from each patient’s digested and cryopreserved tumor, ITIL-168 is an autologous TIL cell therapy manufactured to offer an unrestricted T-cell receptor repertoire. A single-center, compassionate use clinical series demonstrated the feasibility and clinical utility of an earlier version of ITIL-168, with a high overall response rate among pts previously treated with PD-1 inhibitor (PD-1i) therapy (58%, n = 12; Pillai M et al. Ann Oncol. 2021;32[suppl 5]:S882). DELTA-1 (NCT05050006) is a global, multicenter phase 2 study to evaluate efficacy and safety of ITIL-168 in pts with cutaneous melanoma relapsed or refractory to a PD-1i, pts intolerant to a PD-1i, and pts whose current best response to a PD-1i is stable disease. Methods: Pts aged ≥18 years with histologically confirmed advanced cutaneous melanoma, ECOG performance status 0-1, and adequate organ function will be enrolled in 1 of 3 cohorts. Cohort 1 (n≈80) will include pts who relapsed after or were refractory to ≥1 prior line of systemic therapy, including a PD-1i and, if BRAF-mutated, a BRAFi ± MEKi. Cohorts 2 and 3 (n≈25 each) will include pts intolerant to PD-1i and those with stable disease after ≥4 doses of PD-1i, respectively. After tumor resection for TIL harvest, pts must have ≥1 remaining measurable lesion per RECIST 1.1. Pts with uveal, acral, or mucosal melanoma, prior allogeneic transplant or cell therapy, and with central nervous system (CNS) disorder or symptomatic and/or untreated CNS metastases are ineligible. Pts will receive 5 days of lymphodepleting chemotherapy (cyclophosphamide ×2 days overlapping with fludarabine ×5 days) followed by a single ITIL-168 infusion (≥5×109 cells) and supportive short-course, high-dose IL-2. The primary endpoint is objective response rate (ORR) per central review. Secondary endpoints include duration of response, progression-free survival, overall survival, disease control rate, TIL persistence, and safety. Hypothesis testing of ORR will be performed for cohort 1. The primary analysis will occur when all pts in the cohort 1 modified intent-to-treat population have been followed for ≥6 months after the first posttreatment disease assessment. DELTA-1 opened for enrollment in September 2021. Updated site information will be given at the time of presentation. Clinical trial information: NCT05050006.