Background Investigational autologous TIL cell therapies have shown promise in patients with advanced cutaneous melanoma and persistent disease after checkpoint inhibitor therapy, a population with a high unmet medical need.1,2 Made from autologous digested and cryopreserved tumor, ITIL-168 is a TIL cell therapy manufactured to offer an unrestricted T-cell receptor repertoire. DELTA-1 (NCT05050006) is a global, multicenter, phase 2 study evaluating efficacy and safety of ITIL-168 in patients with cutaneous melanoma relapsed or refractory to a PD-1i, patients intolerant to a PD-1i, and patients with stable disease on a PD-1i.
Methods Adult patients with histologically confirmed advanced cutaneous melanoma and ECOG performance status 0-1 will be enrolled in 1 of 3 cohorts. Cohort 1 (n≈80) will include patients 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 patients intolerant to PD-1i and those with stable disease after ≥4 doses of PD-1i, respectively. After tumor harvest, patients must have ≥1 measurable lesion per RECIST 1.1. Noncutaneous melanoma, certain prior therapies, and patients with symptomatic and/or untreated central nervous system metastases are ineligible. Patients will receive 5 days of lymphodepleting chemotherapy (cyclophosphamide ×2 days overlapping with fludarabine ×5 days) followed by a single ITIL-168 infusion and supportive 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 ≥6 months after the first posttreatment disease assessment of patients in the cohort 1 modified intent-to-treat population. Enrollment has expanded into Canada and Europe.
Acknowledgements Medical writing support was provided by Christopher Waldapfel, PharmD, of Instil Bio, Inc. and Phylicia Aaron, PhD, of Nexus Global Group Science, with funding from Instil Bio, Inc.
Schadendorf D, van Akkoi ACJ, Berking C, et al. Melanoma. Lancet. 2018;392(10151):971-984.
Borch TH, Anderson R, Ellebaek E, et al. Future role for adoptive T-cell therapy in checkpoint inhibitor-resistant metastatic melanoma. J Immunother Cancer. 2020;8(2):e000668.
Ethics Approval All patients will provide written informed consent. The study will be approved by the Institutional Review Board/Independent Ethics Committee at each site and conducted in accordance with the Good Clinical Practice Guidelines of the International Council for Harmonisation.
Consent N/A; the abstract does not contain sensitive or identifiable patient information.
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