ITIL-168 in Advanced Melanoma (DELTA-1)

• ClinicalTrials.gov Identifier: NCT05050006
• Recruitment Status: Terminated
• First Posted: September 20, 2021
• Last Update Posted: March 15, 2023
• Sponsor: Instil Bio
• Information provided by (Responsible Party): Instil Bio

Tracking Information

• First Submitted Date: September 9, 2021
• First Posted Date: September 20, 2021
• Last Update Posted Date: March 15, 2023
• Actual Study Start Date: October 7, 2021
• Actual Primary Completion Date: February 27, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 9, 2021)

Objective response rate [ Time Frame: Up to 60 months ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 9, 2021)

• Duration of Response [ Time Frame: Up to 60 months ]
  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.
• Progression-free Survival [ Time Frame: Up to 60 months ]
  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.
• Overall Survival [ Time Frame: Up to 60 months ]
  Overall survival (OS) is defined as the time from the ITIL-168 infusion date to the date of death from any cause.
• ORR as determined by investigators [ Time Frame: Up to 60 months ]
  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.
• Frequency, duration, and severity of ITIL-168 treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest [ Time Frame: Up to 60 months ]
• Disease Control Rate [ Time Frame: Up to 60 months ]
  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.
• Best Overall Response [ Time Frame: Up to 60 months ]
• Time to Response [ Time Frame: Up to 60 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ITIL-168 in Advanced Melanoma
• Official Title: 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)
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

All enrolled participants are assigned to be treated with a single dose of ITIL-168

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Advanced Cutaneous Melanoma

Intervention

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.

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 13, 2023): 29
• Original Estimated Enrollment (submitted: September 9, 2021): 130
• Actual Study Completion Date: February 27, 2023
• Actual Primary Completion Date: February 27, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United Kingdom, United States

Administrative Information

• NCT Number: NCT05050006
• Other Study ID Numbers: ITIL-168-101; 2020-003862-37 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Instil Bio
• Original Responsible Party: Same as current
• Current Study Sponsor: Instil Bio
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Instil Study Director; Instil Bio, Inc.

• PRS Account: Instil Bio
• Verification Date: March 2023