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

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

Detailed Description
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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.

Official Title
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A Phase 1b Study of TBio-4101 (Autologous Selected and Expanded Tumor-Infiltrating Lymphocytes [TIL]) and Pembrolizumab in Patients With Advanced Solid Tumor Malignancies (STARLING)

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

Intervention / Treatment
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* Biological: TBio-4101
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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 exclusion criteria exist

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients enrolled into a Cohort based on malignancy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Breast Cancer<br>Patients with locally advanced or metastatic breast cancer that has failed or is intolerant to standard of care therapies. Includes, HER2+, HER 2-, TNBC. | Biological: TBio-4101<br>* 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.<br>* Other names: TIL, autologous, tumor-reactive, T-cell product;Drug: Pembrolizumab<br>* Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.<br>* Other names: Keytruda;|
| Experimental: Colorectal carcinoma<br>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. | Biological: TBio-4101<br>* 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.<br>* Other names: TIL, autologous, tumor-reactive, T-cell product;Drug: Pembrolizumab<br>* Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.<br>* Other names: Keytruda;|
| Experimental: Uveal Melanoma<br>Patients with advanced, metastatic uveal melanoma. | Biological: TBio-4101<br>* 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.<br>* Other names: TIL, autologous, tumor-reactive, T-cell product;Drug: Pembrolizumab<br>* Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.<br>* Other names: Keytruda;|
| Experimental: Cutaneous Melanoma<br>Patients with cutaneous melanoma who have experienced disease progression following a PD-1 or PD-L1 inhibitor. | Biological: TBio-4101<br>* 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.<br>* Other names: TIL, autologous, tumor-reactive, T-cell product;Drug: Pembrolizumab<br>* Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.<br>* Other names: Keytruda;|
| Experimental: Non-Small Cell Lung Cancer<br>Patients with non-small cell lung cancer who have experienced disease progression following platinum containing chemotherapy and/or PD-1 or PD-L1 inhibitor. | Biological: TBio-4101<br>* 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.<br>* Other names: TIL, autologous, tumor-reactive, T-cell product;Drug: Pembrolizumab<br>* Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.<br>* Other names: Keytruda;|
| Experimental: Head and Neck Squamous Cell Carcinoma<br>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. | Biological: TBio-4101<br>* 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.<br>* Other names: TIL, autologous, tumor-reactive, T-cell product;Drug: Pembrolizumab<br>* Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | The incidence of treatment-emergent adverse events will be tabulated using NCI CTCAE v5.0 | 25 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with a response (ORR) | 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 | 25 months | 
| Estimated Disease Control Rate (DCR) | 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 | 25 months | 
| Estimated Duration of Response (DoR) | 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, | 25 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MSS-CRC, TIL, Tumor infiltrating lymphocyte, TNBC, HR+ Breast, ER+ Breast, MSI-CRC, personalized medicine, ocular melanoma