ITIL-168 in Advanced Solid Tumors (DELTA-2)

A Phase 1, Open-Label, Multicenter Study Evaluating the Safety, Feasibility, and Preliminary Efficacy of ITIL-168 With Pembrolizumab in Subjects With Advanced Solid Tumors

DELTA-2 is a phase 1 clinical trial to evaluate the safety, feasibility, and preliminary efficacy of ITIL-168 with pembrolizumab in participants with advanced cancer whose disease has progressed after standard therapy. ITIL-168 is a cell therapy derived from a patient's own tumor-infiltrating immune cells (lymphocytes; TILs).

Study Overview

• Status: Withdrawn
• Conditions: Cervical Cancer; Non-small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Biological: ITIL-168

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Histologically documented advanced (metastatic and/or unresectable) cervical cancer, HNSCC, or NSCLC.
• Cohort 1: Participants with cervical cancer whose disease progressed during or after at least 1 prior line of chemotherapy.
• Cohort 2: Participants with HNSCC whose disease progressed during or after chemotherapy that must have included a platinum agent and previous CPI.
• Cohort 3: Participants with NSCLC whose disease progressed during or after 1 prior line of platinum-based chemotherapy and a CPI. Participants with targetable mutations (e.g. EGFR/ALK) are required to have progressed on targeted therapy and platinum-based chemotherapy
• 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
• Neuroendocrine carcinoma, nasopharyngeal carcinoma, squamous cell carcinoma of the lip, or histopathology with neuroendocrine differentiation
• 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, IL-2, of CPI

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; Participants with cervical cancer whose disease has progressed during or after treatment with platinum-based chemotherapy. Participants with combined positive score ≥ 1 should also have disease that has progressed during or after treatment with CPI.	Biological: ITIL-168; ITIL-168 is a cell therapy product derived from a participant's own TILs. A portion of tumor is resected to make a personalized ITIL-168 product. If appropriate, participants may receive bridging therapy after recovering from the tumor resection during ITIL-168 manufacturing. Once ITIL-168 has been made, the participant is treated with up to 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. Drug: Pembrolizumab Participants will receive 1 dose of pembrolizumab following tumor resection prior to receiving ITIL-168, and additional doses for up to a year after ITIL-168 infusion.
Experimental: Cohort 2; Participants with head and neck squamous-cell carcinoma (HNSCC) whose disease has progressed during or after platinum-based chemotherapy and previous CPI.	Biological: ITIL-168; ITIL-168 is a cell therapy product derived from a participant's own TILs. A portion of tumor is resected to make a personalized ITIL-168 product. If appropriate, participants may receive bridging therapy after recovering from the tumor resection during ITIL-168 manufacturing. Once ITIL-168 has been made, the participant is treated with up to 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. Drug: Pembrolizumab Participants will receive 1 dose of pembrolizumab following tumor resection prior to receiving ITIL-168, and additional doses for up to a year after ITIL-168 infusion.
Experimental: Cohort 3; Participants with non-small cell lung cancer (NSCLC) whose disease has progressed during or after platinum-based chemotherapy and a CPI. Participants with targetable mutations (e.g. EGFR/ALK) are required to have disease which has progressed on targeted therapy and platinum-based chemotherapy.	Biological: ITIL-168; ITIL-168 is a cell therapy product derived from a participant's own TILs. A portion of tumor is resected to make a personalized ITIL-168 product. If appropriate, participants may receive bridging therapy after recovering from the tumor resection during ITIL-168 manufacturing. Once ITIL-168 has been made, the participant is treated with up to 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. Drug: Pembrolizumab Participants will receive 1 dose of pembrolizumab following tumor resection prior to receiving ITIL-168, and additional doses for up to a year after ITIL-168 infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency and severity of ITIL-168 treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 investigator review.	Up to 60 months
Duration of response	For participants 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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2022
• Primary Completion (Actual): December 8, 2022
• Study Completion (Actual): December 8, 2022

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Estimate): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Cell Therapy; Tumor Infiltrating Lymphocytes; Non-small cell lung cancer (NSCLC); pembrolizumab; IL-2; Cervical cancer; Immuno-oncology; TIL; Autologous Adoptive Cell Therapy; T-cell therapy; Cellular Immunotherapy; ITIl-168; Head and neck squamous-cell carcinoma (HNSCC); Checkpoint inhibitor (CPI); PD-1 pathway inhibitors
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Head and Neck Neoplasms; Lung Neoplasms; Neoplasms, Squamous Cell; Uterine Cervical Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: ITIL-168-102

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