ITIL-306 in Advanced Solid Tumors

Study Overview
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Brief Summary
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ITIL-306-201 is a phase 1a/1b, multicenter, clinical trial evaluating the safety and feasibility of ITIL-306 in adult participants with advanced solid tumors whose disease has progressed after standard therapy. ITIL-306 is a cell therapy derived from a participant's own tumor-infiltrating immune cells (lymphocytes; TILs) and contains a unique molecule designed to increase TIL activity when it encounters folate receptor α (FOLR1) on the tumor.

Official Title
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A Phase 1a/1b, Open-Label, Multicenter Study Evaluating the Safety and Feasibility of ITIL-306 in Subjects With Advanced Solid Tumors

Conditions
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Epithelial Ovarian Cancer, Non-small Cell Lung Cancer, Renal Cell Carcinoma

Intervention / Treatment
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* Biological: ITIL-306


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically documented advanced (metastatic and/or unresectable) disease as appropriate per cohort. Phase 1a Dose Escalation: High-grade serous epithelial carcinoma of the ovary, fallopian tube, or peritoneum, adenocarcinoma of the lung, or clear-cell renal cell carcinoma. Phase 1b Expansion: Cohort 1: High grade serous, endometrioid, or clear cell epithelial carcinoma of the ovary, fallopian tube, or peritoneum. Cohort 2: Squamous-cell carcinoma or adenocarcinoma of the lung. Cohort 3: Clear cell or papillary RCC. Disease must have unequivocally progressed during or after at least 1 prior line of systemic therapy that must include the following parameters (by indication): Phase 1a dose escalation and Phase 1b Cohort 1: Participants with EOC whose disease has progressed during or after 1 prior line (at least 4 cycles) of platinum-based chemotherapy and had disease progression within 6 months from the last dose of the platinum agent. Participants who received 2 or more lines of platinum therapy must have disease which has progressed on or within 6 months after the date of the last dose of the platinum agent. Participants with BRCA-mutated EOC must have received previous PARP inhibitor therapy. Phase 1a dose escalation and Phase 1b Cohort 2: Participants with NSCLC whose disease has progressed after 1 prior line of platinum-based doublet chemotherapy and a CPI. Participants with targetable mutations (e.g. EGFR/ALK/KRAS) are required to have progressed on targeted therapy in addition to a platinum-based doublet chemotherapy Phase 1a dose escalation and Phase 1b Cohort 3: Participants with RCC whose disease has progressed after 1 prior line of antiangiogenic therapy and a PD-1-axis inhibitor. 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 Phase 1a: EOC of the following subtypes: low-grade, endometrioid, clear cell, mucinous, sarcomatous, or mixed. NSCLC of the following subtypes: squamous, neuroendocrine differentiation. RCC of the following subtypes: nonclear-cell RCC Phase 1b: Cohort 1: Participants with mucinous, sarcomatous, and low-grade EOC. Cohort 2: Participants with small cell lung cancer, or NSCLC with neuroendocrine differentiation Cohort 3: Participants with nonclear-cell RCC, except papillary RCC 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, dimethyl sulfoxide (DMSO), human serum albumin (HAS), phosphate buffer or gentamycin

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: Phase 1a: Dose Escalation<br>Various doses will be tested in participants with EOC, NSCLC and RCC. | Biological: ITIL-306<br>* ITIL-306 is a cell therapy product derived from a participant's own TILs and contains a unique molecule designed to increase TIL activity when it encounters FOLR1 on the tumor. A portion of the participant's tumor is surgically removed to make a personalized ITIL-306 product. Once ITIL-306 has been made, the participant is treated with 3 days of lymphodepleting chemotherapy including cyclophosphamide and fludarabine, followed by 2 days of rest then a single infusion of ITIL-306.<br>|
| Experimental: Phase 1b: Expansion<br>Cohort 1: Participants with epithelial ovarian cancer (EOC) Cohort 2: Participants with non-small cell lung cancer (NSCLC) Cohort 3: Participants with renal cell carcinoma (RCC) | Biological: ITIL-306<br>* ITIL-306 is a cell therapy product derived from a participant's own TILs and contains a unique molecule designed to increase TIL activity when it encounters FOLR1 on the tumor. A portion of the participant's tumor is surgically removed to make a personalized ITIL-306 product. Once ITIL-306 has been made, the participant is treated with 3 days of lymphodepleting chemotherapy including cyclophosphamide and fludarabine, followed by 2 days of rest then a single infusion of ITIL-306.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of ITIL-306 treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest (AESI) |  | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | 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 (DOR) | For participants who experience an objective response, DOR is defined as the time from their first objective response to disease progression or death. | Up to 60 months | 
| Progression-free survival (PFS) | PFS is defined as the time from the ITIL-306 infusion date to the date of disease progression or death from any cause. | Up to 60 months | 
| Overall Survival (OS) | OS is defined as the time from the ITIL-306 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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TIL, ITIL-306, Cell Therapy, Epithelial ovarian cancer (EOC), Non-small cell lung cancer (NSCLC), Renal cell carcinoma (RCC), Fallopian tube carcinoma, Tumor Infiltrating Lymphocytes, T-cell therapy, Folate receptor α (FOLR1), Anti-folate receptor α (FOLR1), Autologous Adoptive Cell Therapy, Checkpoint, PD-1 axis inhibitor, Peritoneal carcinoma, Cellular Immunotherapy, Immuno-oncology, Costimulatory antigen receptor (CoStAR)