A Study of TBio-4101 (TIL) and Pembrolizumab in Patients With Advanced Solid Tumors
- Conditions
- Breast CancerColorectal CancerCutaneous MelanomaUveal MelanomaNon-Small Cell Lung CancerHead and Neck Squamous Cell Carcinoma
- Interventions
- Registration Number
- NCT05576077
- Lead Sponsor
- Turnstone Biologics, Corp.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 31
- 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
- Additional inclusion criteria exist
Key
- 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
- Additional exclusion criteria exist
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Breast Cancer TBio-4101 Patients with locally advanced or metastatic breast cancer that has failed or is intolerant to standard of care therapies. Includes, HER2+, HER 2-, TNBC. Colorectal carcinoma TBio-4101 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. Uveal Melanoma TBio-4101 Patients with advanced, metastatic uveal melanoma. Non-Small Cell Lung Cancer TBio-4101 Patients with non-small cell lung cancer who have experienced disease progression following platinum containing chemotherapy and/or PD-1 or PD-L1 inhibitor. Head and Neck Squamous Cell Carcinoma TBio-4101 * 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. Cutaneous Melanoma TBio-4101 Patients with cutaneous melanoma who have experienced disease progression following a PD-1 or PD-L1 inhibitor. Breast Cancer Pembrolizumab Patients with locally advanced or metastatic breast cancer that has failed or is intolerant to standard of care therapies. Includes, HER2+, HER 2-, TNBC. Colorectal carcinoma Pembrolizumab 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. Uveal Melanoma Pembrolizumab Patients with advanced, metastatic uveal melanoma. Cutaneous Melanoma Pembrolizumab Patients with cutaneous melanoma who have experienced disease progression following a PD-1 or PD-L1 inhibitor. Non-Small Cell Lung Cancer Pembrolizumab Patients with non-small cell lung cancer who have experienced disease progression following platinum containing chemotherapy and/or PD-1 or PD-L1 inhibitor. Head and Neck Squamous Cell Carcinoma Pembrolizumab * 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.
- Primary Outcome Measures
Name Time Method Safety and tolerability 25 months The incidence of treatment-emergent adverse events will be tabulated using NCI CTCAE v5.0
- Secondary Outcome Measures
Name Time Method Proportion of patients with a response (ORR) 25 months Percentage of all patients and within each cancer indication with a CR or PR as assessed by the independent central radiologist using RECIST 1.1 and iRECIST
Estimated Disease Control Rate (DCR) 25 months Portion of patient whose best response is a CR, PR, or stable disease (SD) as assessed by the independent central radiologist using RECIST v1.1 and iRECIST
Estimated Duration of Response (DoR) 25 months Duration of response, as measured in weeks, that patients with a CR or PR have no progressed (PD), as assessed by the independent central radiologist using RECIST v1.1 and iRECIST,
Trial Locations
- Locations (13)
University of Miami
🇺🇸Miami, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Orlando Health
🇺🇸Orlando, Florida, United States
Providence Cancer Institute
🇺🇸Portland, Oregon, United States
Allegheny Research Institute
🇺🇸Pittsburgh, Pennsylvania, United States
University of California Irvine
🇺🇸Irvine, California, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
Montreal University Hospital Center
🇨🇦Montréal, Quebec, Canada