ITIL-306 in Advanced Solid Tumors
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1a: Dose Escalation Various doses will be tested in participants with EOC, NSCLC and RCC. |
Biological: ITIL-306
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.
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| Experimental: Phase 1b: Expansion 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
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.
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Outcome Measures
Primary Outcome Measures
- 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
- Objective response rate (ORR) [Up to 60 months]
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.
- Duration of response (DOR) [Up to 60 months]
For participants who experience an objective response, DOR is defined as the time from their first objective response to disease progression or death.
- Progression-free survival (PFS) [Up to 60 months]
PFS is defined as the time from the ITIL-306 infusion date to the date of disease progression or death from any cause.
- Overall Survival (OS) [Up to 60 months]
OS is defined as the time from the ITIL-306 infusion date to the date of death from any cause.
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Histologically documented advanced (metastatic and/or unresectable) disease as appropriate per cohort.
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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.
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Phase 1b Expansion:
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Cohort 1: High grade serous, endometrioid, or clear cell epithelial carcinoma of the ovary, fallopian tube, or peritoneum.
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Cohort 2: Squamous-cell carcinoma or adenocarcinoma of the lung.
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Cohort 3: Clear cell or papillary RCC.
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Disease must have unequivocally progressed during or after at least 1 prior line of systemic therapy that must include the following parameters (by indication):
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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.
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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
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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.
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Medically suitable for surgical resection of tumor tissue
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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
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Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
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Adequate bone marrow and organ function
Key Exclusion Criteria:
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History of another primary malignancy within the previous 3 years
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Phase 1a:
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EOC of the following subtypes: low-grade, endometrioid, clear cell, mucinous, sarcomatous, or mixed.
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NSCLC of the following subtypes: squamous, neuroendocrine differentiation.
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RCC of the following subtypes: nonclear-cell RCC
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Phase 1b:
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Cohort 1: Participants with mucinous, sarcomatous, and low-grade EOC.
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Cohort 2: Participants with small cell lung cancer, or NSCLC with neuroendocrine differentiation
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Cohort 3: Participants with nonclear-cell RCC, except papillary RCC
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Previously received an allogeneic stem cell transplant or organ allograft
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Previously received TIL or engineered cell therapy (eg, CAR T-cell)
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Significant cardiac disease
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Stroke or transient ischemic attack within 12 months of enrollment
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History of significant central nervous system (CNS) disorder
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Symptomatic and/or untreated CNS metastases
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History of significant autoimmune disease within 2 years prior to enrollment
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Known history of severe, immediate hypersensitivity reaction attributed to cyclophosphamide, fludarabine, dimethyl sulfoxide (DMSO), human serum albumin (HAS), phosphate buffer or gentamycin
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 2 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Instil Bio
Investigators
- Study Director: Instil Study Director, Instil Bio, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ITIL-306-201