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ITIL-306 in Advanced Solid Tumors

Primary Purpose

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

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ITIL-306
Sponsored by
Instil Bio
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epithelial Ovarian Cancer focused on measuring 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)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Washington University School of Medicine
  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phase 1a: Dose Escalation

Phase 1b: Expansion

Arm Description

Various doses will be tested in participants with EOC, NSCLC and RCC.

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)

Outcomes

Primary Outcome Measures

Frequency and severity of ITIL-306 treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest (AESI)

Secondary Outcome Measures

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.
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.
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.
Overall Survival (OS)
OS is defined as the time from the ITIL-306 infusion date to the date of death from any cause.

Full Information

First Posted
May 25, 2022
Last Updated
February 22, 2023
Sponsor
Instil Bio
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1. Study Identification

Unique Protocol Identification Number
NCT05397093
Brief Title
ITIL-306 in Advanced Solid Tumors
Official Title
A Phase 1a/1b, Open-Label, Multicenter Study Evaluating the Safety and Feasibility of ITIL-306 in Subjects With Advanced Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 24, 2022 (Actual)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
November 2039 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instil Bio

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epithelial Ovarian Cancer, Non-small Cell Lung Cancer, Renal Cell Carcinoma
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
51 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1a: Dose Escalation
Arm Type
Experimental
Arm Description
Various doses will be tested in participants with EOC, NSCLC and RCC.
Arm Title
Phase 1b: Expansion
Arm Type
Experimental
Arm Description
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)
Intervention Type
Biological
Intervention Name(s)
ITIL-306
Intervention Description
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.
Primary Outcome Measure Information:
Title
Frequency and severity of ITIL-306 treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest (AESI)
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
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.
Time Frame
Up to 60 months
Title
Duration of response (DOR)
Description
For participants who experience an objective response, DOR is defined as the time from their first objective response to disease progression or death.
Time Frame
Up to 60 months
Title
Progression-free survival (PFS)
Description
PFS is defined as the time from the ITIL-306 infusion date to the date of disease progression or death from any cause.
Time Frame
Up to 60 months
Title
Overall Survival (OS)
Description
OS is defined as the time from the ITIL-306 infusion date to the date of death from any cause.
Time Frame
Up to 60 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Instil Study Director
Organizational Affiliation
Instil Bio, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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ITIL-306 in Advanced Solid Tumors

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