ITIL-168 in Advanced Solid Tumors

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Cervical Cancer, Head and Neck Squamous Cell Carcinoma, Non-small Cell Lung Cancer

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 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

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>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<br>* 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.<br>|
| Experimental: Cohort 2<br>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<br>* 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.<br>|
| Experimental: Cohort 3<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ITIl-168, Cell Therapy, Cervical cancer, Head and neck squamous-cell carcinoma (HNSCC), Non-small cell lung cancer (NSCLC), Autologous Adoptive Cell Therapy, Cellular Immunotherapy, Immuno-oncology, Tumor Infiltrating Lymphocytes, TIL, T-cell therapy, IL-2, pembrolizumab, Checkpoint inhibitor (CPI), PD-1 pathway inhibitors