ITIL-306 in Advanced Solid Tumors

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05397093
• Other study ID #: ITIL-306-201
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 24, 2022
• Est. completion date: November 2039

Study information

• Verified date: March 2024
• Source: Instil Bio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 51
• Est. completion date: November 2039
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Ovarian Epithelial
• Carcinoma, Renal Cell
• Epithelial Ovarian Cancer
• Non-small Cell Lung Cancer
• Ovarian Neoplasms
• Renal Cell Carcinoma

Intervention

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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Instil Bio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency and severity of ITIL-306 treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest (AESI)		Up to 24 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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