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

Breast Cancer Clinical Trial

— STARLING  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05576077
• Other study ID #: TBio-4101-001
• Status: Recruiting
• Phase: Phase 1
• Start date: January 17, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: January 2024
• Source: Turnstone Biologics, Corp.
• Contact: Thelma Bueno
• Phone: (843) 321-8490
• Email: STARLINGTumorStudy[@]kapadi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.

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

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of California Irvine	Irvine	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Orlando Health	Orlando	Florida
United States	Allegheny Research Institute	Pittsburgh	Pennsylvania
United States	Providence Healthcare Research Institute	Portland	Oregon
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Turnstone Biologics, Corp.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability	The incidence of treatment-emergent adverse events will be tabulated using NCI CTCAE v5.0	25 months
Secondary	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
Secondary	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
Secondary	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