ITIL-168 in Advanced Melanoma (DELTA-1)

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)

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).

Study Overview

• Status: Terminated
• Conditions: Advanced Cutaneous Melanoma
• Intervention / Treatment: Biological: ITIL-168

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
• United Kingdom
  • England
    • Cambridge, England, United Kingdom, CB2 0QQ
      • Cambridge University Hospital NHS Foundation Trust - Addenbrooke's Hospital
• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego, Moores Cancer Center
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
    • Los Angeles, California, United States, 90033
      • USC - Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90095
      • UCLA Health - Westwood Cancer Care
    • Stanford, California, United States, 94305
      • Stanford Cancer Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado - Anschutz Cancer Pavilion
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • The University of Miami - Sylvester Comprehensive Cancer Center
    • Orlando, Florida, United States, 32806
      • Orlando Health Cancer Institute
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Cancer Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Chicago
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville, James Graham Brown Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota, Masonic Cancer Center
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Atlantic Health System - Morristown Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic - Taussig Cancer Center
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's University Health Network
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Patients who relapsed after or were refractory to at least 1 prior line of systemic therapy including a PD-1 inhibitor.	Biological: ITIL-168; 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.
Experimental: Cohort 2; Patients who were intolerant to a PD-1 inhibitor and have persistent disease after stopping PD-1 therapy.	Biological: ITIL-168; 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.
Experimental: Cohort 3; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Instil Bio
• Investigators: Study Director: Instil Study Director, Instil Bio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2021
• Primary Completion (Actual): February 27, 2023
• Study Completion (Actual): February 27, 2023

Study Registration Dates

• First Submitted: September 9, 2021
• First Submitted That Met QC Criteria: September 9, 2021
• First Posted (Actual): September 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cell Therapy; melanoma; Tumor Infiltrating Lymphocytes; IL-2; Immuno-oncology; TIL; Autologous Adoptive Cell Transfer; Autologous Adoptive Cell Therapy; Autologous cell therapy; T-cell therapy; ITIL-168; Cellular Immunotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma
• Other Study ID Numbers: ITIL-168-101; 2020-003862-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No