A Study of TBio-4101 (TIL) and Pembrolizumab in Patients With Advanced Solid Tumors

NCT ID: NCT05576077

Last Updated: 2025-03-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-17
• Study Completion Date: 2025-02-24

Brief Summary

A multicenter trial to investigate TBio-4101, an autologous, neoantigen-selected, tumor-reactive TIL product, in patients with advanced solid malignancies.

Detailed Description

This is a Phase 1 study to investigate TBio-4101. TBio-4101 is an autologous tumor infiltrating lymphocyte (TIL) therapy that utilizes tumor specific antigens to select, sort, and expand patient-specific tumor-reactive T-cells to be reinfused into the patient. The adoptive cell therapy is further enhanced through the use of non-myeloablative chemotherapy prior to TIL infusion, followed by the TIL plus IL-2 infusion. Low-dose radiation therapy is administered prior to and after TIL plus IL-2 infusion. Pembrolizumab is provided after the resolution of IL-2 toxicities. The trial is open to solid tumors of varying tumor mutational burdens.

Conditions

Breast Cancer; Colorectal Cancer; Uveal Melanoma; Cutaneous Melanoma; Non-Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Breast Cancer

Patients with locally advanced or metastatic breast cancer that has failed or is intolerant to standard of care therapies. Includes, HER2+, HER 2-, TNBC.

Group Type: EXPERIMENTAL

TBio-4101

Intervention Type: BIOLOGICAL

TBio-4101 is an autologous selected and expanded tumor infiltrating lymphocyte (TIL) product generated following ex vivo expansion of tumor reactive TIL population found in tumor harvest. After preparation with non-myeloablative lymphodepletion chemotherapy (cyclophosphamide and fludarabine) followed by low dose radiation,TBio-4101, and IL-2.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.

Colorectal carcinoma

Patients with advanced, metastatic colorectal adenocarcinoma who have failed or are intolerant to at least one line of therapy that included either irinotecan or oxaliplatin.

Group Type: EXPERIMENTAL

TBio-4101

Intervention Type: BIOLOGICAL

TBio-4101 is an autologous selected and expanded tumor infiltrating lymphocyte (TIL) product generated following ex vivo expansion of tumor reactive TIL population found in tumor harvest. After preparation with non-myeloablative lymphodepletion chemotherapy (cyclophosphamide and fludarabine) followed by low dose radiation,TBio-4101, and IL-2.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.

Uveal Melanoma

Patients with advanced, metastatic uveal melanoma.

Group Type: EXPERIMENTAL

TBio-4101

Intervention Type: BIOLOGICAL

TBio-4101 is an autologous selected and expanded tumor infiltrating lymphocyte (TIL) product generated following ex vivo expansion of tumor reactive TIL population found in tumor harvest. After preparation with non-myeloablative lymphodepletion chemotherapy (cyclophosphamide and fludarabine) followed by low dose radiation,TBio-4101, and IL-2.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.

Cutaneous Melanoma

Patients with cutaneous melanoma who have experienced disease progression following a PD-1 or PD-L1 inhibitor.

Group Type: EXPERIMENTAL

TBio-4101

Intervention Type: BIOLOGICAL

TBio-4101 is an autologous selected and expanded tumor infiltrating lymphocyte (TIL) product generated following ex vivo expansion of tumor reactive TIL population found in tumor harvest. After preparation with non-myeloablative lymphodepletion chemotherapy (cyclophosphamide and fludarabine) followed by low dose radiation,TBio-4101, and IL-2.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.

Non-Small Cell Lung Cancer

Patients with non-small cell lung cancer who have experienced disease progression following platinum containing chemotherapy and/or PD-1 or PD-L1 inhibitor.

Group Type: EXPERIMENTAL

TBio-4101

Intervention Type: BIOLOGICAL

TBio-4101 is an autologous selected and expanded tumor infiltrating lymphocyte (TIL) product generated following ex vivo expansion of tumor reactive TIL population found in tumor harvest. After preparation with non-myeloablative lymphodepletion chemotherapy (cyclophosphamide and fludarabine) followed by low dose radiation,TBio-4101, and IL-2.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.

Head and Neck Squamous Cell Carcinoma

• Patients with head and neck squamous cell carcinoma who have received no prior therapy for metastatic disease
• Patients with head and neck squamous cell carcinoma who are PD-1/PD-L1 inhibitor naïve at the time of TIL harvest and will be treated with TBio-4101 at the time of progression, inadequate response or intolerance to the PD-1/PD-L1 inhibitor-based standard of care regimen given on study.

Group Type: EXPERIMENTAL

TBio-4101

Intervention Type: BIOLOGICAL

TBio-4101 is an autologous selected and expanded tumor infiltrating lymphocyte (TIL) product generated following ex vivo expansion of tumor reactive TIL population found in tumor harvest. After preparation with non-myeloablative lymphodepletion chemotherapy (cyclophosphamide and fludarabine) followed by low dose radiation,TBio-4101, and IL-2.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.

Interventions

TBio-4101

TBio-4101 is an autologous selected and expanded tumor infiltrating lymphocyte (TIL) product generated following ex vivo expansion of tumor reactive TIL population found in tumor harvest. After preparation with non-myeloablative lymphodepletion chemotherapy (cyclophosphamide and fludarabine) followed by low dose radiation,TBio-4101, and IL-2.

Intervention Type: BIOLOGICAL

Pembrolizumab

Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.

Intervention Type: DRUG

Other Intervention Names

TIL, autologous, tumor-reactive, T-cell product; Keytruda

Eligibility Criteria

Inclusion Criteria

• Advanced or metastatic breast carcinoma, colorectal adenocarcinoma, uveal melanoma, cutaneous melanoma, non-small cell lung cancer, or head and neck squamous cell carcinoma that has failed or is refractory to standard of care therapy
• Have at least one target lesion that can be used for response assessments and have at least 1 tumor amenable for tissue harvest for TIL manufacturing.
• ECOG performance status of 0 or 1
• Demonstrate adequate organ function

Exclusion Criteria

• Known additional malignancy that is progressing or has required active treatment within the past 3 years
• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy or any other form of immunosuppressive
• Currently infected with HIV Type 1 and Type 2, hepatitis B virus (HBV), hepatitis C virus (HCV), treponema pallidum (e.g., syphilis), West Nile virus (WNV), Human T-lymphotropic virus types 1 or II (HTLV I/II), or cytomegalovirus (CMV)
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable
• Serious cardiac condition, such as uncontrolled hypertension, concurrent congestive heart failure, prior history of Class III/IV cardiac disease (New York Heart Association [NYHA]), history of cardiac ischemia within the past 6 months, or prior history of cardiac arrhythmia requiring treatment. Patients who are > 60 years of age must undergo cardiology clearance exam and cardiac stress test.
• Prior cell therapy or organ transplant
• History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, IL-2, or pembrolizumab, or any of their constituents
• LVEF ≤ 45%
• FEV1 ≤ 60% of predicted value and DLCO (corrected) < 60% of predicted value
• Chronic anti-coagulant therapy that cannot either be discontinued or temporarily changed

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Turnstone Biologics, Corp.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ines Verdon, MD

Role: STUDY_DIRECTOR

Turnstone Biologics, Corp.

Locations

University of California Irvine

Irvine, California, United States

Memorial Healthcare System

Hollywood, Florida, United States

University of Miami

Miami, Florida, United States

Orlando Health

Orlando, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

University of Chicago

Chicago, Illinois, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Providence Cancer Institute

Portland, Oregon, United States

Allegheny Research Institute

Pittsburgh, Pennsylvania, United States

MD Anderson Cancer Center

Houston, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Montreal University Hospital Center

Montreal, Quebec, Canada

Countries

United States; Canada

Other Identifiers

TBio-4101-001

Identifier Type: -

Identifier Source: org_study_id