Breast Cancer, Colorectal Cancer, Uveal Melanoma, Cutaneous Melanoma, Non-Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
MSS-CRC, TIL, Tumor infiltrating lymphocyte, TNBC, HR+ Breast, ER+ Breast, MSI-CRC, personalized medicine, ocular melanoma
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.
Interventions
BIOLOGICALTBio-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.
DRUGPembrolizumab
Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.
Sponsors
Turnstone Biologics, Corp.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients enrolled into a Cohort based on malignancy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key 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 * Additional inclusion criteria exist Key
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 * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | 25 months | The incidence of treatment-emergent adverse events will be tabulated using NCI CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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, |
Countries
Canada, United States
Outcome results
None listed