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

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)

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

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Colorectal Cancer; Non-Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Uveal Melanoma; Cutaneous Melanoma
• Intervention / Treatment: Biological: TBio-4101; Drug: Pembrolizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C1
      • Princess Margaret Cancer Centre
  • Quebec
    • Montréal, Quebec, Canada, H2X 0C1
      • Montreal University Hospital Center
• United States
  • California
    • Irvine, California, United States, 92868
      • University of California Irvine
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare System
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32806
      • Orlando Health
    • Tampa, Florida, United States, 33612-9497
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Allegheny Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: 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.; Other Names: TIL, autologous, tumor-reactive, T-cell product; Drug: Pembrolizumab; Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.; Other Names: Keytruda
Experimental: 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.	Biological: 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.; Other Names: TIL, autologous, tumor-reactive, T-cell product; Drug: Pembrolizumab; Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.; Other Names: Keytruda
Experimental: Uveal Melanoma; Patients with advanced, metastatic uveal melanoma.	Biological: 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.; Other Names: TIL, autologous, tumor-reactive, T-cell product; Drug: Pembrolizumab; Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.; Other Names: Keytruda
Experimental: Cutaneous Melanoma; Patients with cutaneous melanoma who have experienced disease progression following a PD-1 or PD-L1 inhibitor.	Biological: 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.; Other Names: TIL, autologous, tumor-reactive, T-cell product; Drug: Pembrolizumab; Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.; Other Names: Keytruda
Experimental: 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.	Biological: 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.; Other Names: TIL, autologous, tumor-reactive, T-cell product; Drug: Pembrolizumab; Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.; Other Names: Keytruda
Experimental: 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.	Biological: 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.; Other Names: TIL, autologous, tumor-reactive, T-cell product; Drug: Pembrolizumab; Pembrolizumab will be administered after TIL infusion and continue every 3-6 weeks for up to 2 years.; Other Names: Keytruda

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Turnstone Biologics, Corp.
• Investigators: Study Director: Ines Verdon, MD, Turnstone Biologics, Corp.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2023
• Primary Completion (Actual): February 4, 2025
• Study Completion (Actual): February 24, 2025

Study Registration Dates

• First Submitted: October 7, 2022
• First Submitted That Met QC Criteria: October 7, 2022
• First Posted (Actual): October 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 7, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: TNBC; ocular melanoma; TIL; personalized medicine; Tumor infiltrating lymphocyte; MSS-CRC; HR+ Breast; ER+ Breast; MSI-CRC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Skin Diseases; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: TBio-4101-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No