ITIL-168 in Advanced Melanoma

Study Overview
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Brief Summary
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DELTA-1 is a phase 2 clinical trial to evaluate the efficacy and safety of ITIL-168 in adult subjects with advanced melanoma who have previously been treated with a PD-1 inhibitor. ITIL-168 is a cell therapy derived from a patient's own tumor-infiltrating immune cells (lymphocytes; TILs).

Official Title
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A Phase 2, Open-label, Multicenter Study Evaluating the Safety and Efficacy of Autologous Tumor-infiltrating Lymphocytes (TILs) in Subjects With Advanced Melanoma (DELTA-1)

Conditions
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Advanced Cutaneous Melanoma

Intervention / Treatment
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* Biological: ITIL-168


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed advanced (unresectable or metastatic) cutaneous melanoma. Cohort 1: Disease that is relapsed after or refractory to at least 1 prior line of systemic therapy that must include a PD-1 inhibitor and, if positive for proto- oncogene BRAF V600 activating mutation, targeted therapy. Cohort 2: Disease that is persistent after discontinuing PD-1 due to toxicity. Patients with a proto-oncogene BRAF V600 activating mutation must have progressed after targeted therapy. Cohort 3: Disease that is stable (SD) after at least 4 doses of a PD-1 inhibitor. Patients with a proto-oncogene BRAF V600 activating mutation must have progressed after targeted therapy. Medically suitable for surgical resection of tumor tissue Following tumor resection for TIL harvest, will have, at minimum, 1 remaining measurable lesion as identified by CT or MRI per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate bone marrow and organ function Key Exclusion Criteria: History of another primary malignancy within the previous 3 years Melanoma of uveal, acral, or mucosal origin Previously received an allogeneic stem cell transplant or organ allograft Previously received TIL or engineered cell therapy ( eg, CAR T-cell) Significant cardiac disease Stroke or transient ischemic attack within 12 months of enrollment History of significant central nervous system (CNS) disorder Symptomatic and/or untreated CNS metastases History of significant autoimmune disease within 2 years prior to enrollment Known history of severe, immediate hypersensitivity reaction attributed to cyclophosphamide, fludarabine, or IL-2.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All enrolled participants are assigned to be treated with a single dose of ITIL-168
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Patients who relapsed after or were refractory to at least 1 prior line of systemic therapy including a PD-1 inhibitor. | Biological: ITIL-168<br>* ITIL-168 is a cell therapy product derived from a patient's own TILs. A tumor sample is removed from each patient to make a personalized ITIL-168 product. Once ITIL-168 has been made, the patient is treated with 5 days of lymphodepleting chemotherapy including cyclophosphamide and fludarabine, followed by a single infusion of ITIL-168, and up to 8 doses of IL-2.<br>|
| Experimental: Cohort 2<br>Patients who were intolerant to a PD-1 inhibitor and have persistent disease after stopping PD-1 therapy. | Biological: ITIL-168<br>* ITIL-168 is a cell therapy product derived from a patient's own TILs. A tumor sample is removed from each patient to make a personalized ITIL-168 product. Once ITIL-168 has been made, the patient is treated with 5 days of lymphodepleting chemotherapy including cyclophosphamide and fludarabine, followed by a single infusion of ITIL-168, and up to 8 doses of IL-2.<br>|
| Experimental: Cohort 3<br>Patients who had a best response of stable disease despite being treated with at least 4 doses of a PD-1 inhibitor in the previous line of therapy. | Biological: ITIL-168<br>* ITIL-168 is a cell therapy product derived from a patient's own TILs. A tumor sample is removed from each patient to make a personalized ITIL-168 product. Once ITIL-168 has been made, the patient is treated with 5 days of lymphodepleting chemotherapy including cyclophosphamide and fludarabine, followed by a single infusion of ITIL-168, and up to 8 doses of IL-2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Objective response rate (ORR), defined as the incidence of a complete response (CR) or a partial response (PR) per a modified Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria, as assessed by central review. | Up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | For subjects who experience an objective response, duration of response (DOR) is defined as the time from their first objective response to disease progression or death. | Up to 60 months | 
| Progression-free Survival | Progression-free survival (PFS) is defined as the time from the ITIL-168 infusion date to the date of disease progression or death from any cause. | Up to 60 months | 
| Overall Survival | Overall survival (OS) is defined as the time from the ITIL-168 infusion date to the date of death from any cause. | Up to 60 months | 
| ORR as determined by investigators | ORR as determined by investigators is defined as the incidence of a CR or a PR per a modified RECIST v1.1, as determined by study investigators. | Up to 60 months | 
| Frequency, duration, and severity of ITIL-168 treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest |  | Up to 60 months | 
| Disease Control Rate | Disease control rate (DCR), defined as the incidence of CR, PR, or stable disease (SD) per a modified RECIST v1.1 criteria, as determined by central review. | Up to 60 months | 
| Best Overall Response |  | Up to 60 months | 
| Time to Response |  | Up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TIL, ITIL-168, Cell Therapy, melanoma, Autologous cell therapy, Cellular Immunotherapy, Autologous Adoptive Cell Transfer, Immuno-oncology, IL-2, Autologous Adoptive Cell Therapy, Tumor Infiltrating Lymphocytes, T-cell therapy