Epithelial Ovarian Cancer, Non-small Cell Lung Cancer, Renal Cell Carcinoma
Conditions
Keywords
ITIL-306, Cell Therapy, Epithelial ovarian cancer (EOC), Non-small cell lung cancer (NSCLC), Renal cell carcinoma (RCC), Fallopian tube carcinoma, Tumor Infiltrating Lymphocytes, TIL, 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)
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.
Interventions
BIOLOGICALITIL-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.
Sponsors
Instil Bio
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
STUDY_DIRECTORInstil Study Director
Instil Bio, Inc.
Outcome results
None listed