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

Sponsor

Turnstone Biologics, Corp. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05576077

Collaborator

(none)

Enrollment

Locations

Arms

17.4

Anticipated Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Colorectal Cancer Uveal Melanoma	Biological: TBio-4101 Drug: Pembrolizumab	Phase 1

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. Pembrolizumab is provided after the resolution of IL-2 toxicities. The trial is open to solid tumors of varying tumor mutational burdens.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients enrolled into a Cohort based on malignancy.Patients enrolled into a Cohort based on malignancy.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jan 17, 2023

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

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 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 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 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 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 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 weeks for up to 2 years. Other Names: Keytruda

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 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 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

Other Names:

TIL, autologous, tumor-reactive, T-cell product

Drug: Pembrolizumab

Pembrolizumab will be administered after TIL infusion and continue every 3 weeks for up to 2 years.

Other Names:

Keytruda

Experimental: Uveal Melanoma

Patients with advanced, metastatic uveal melanoma.

Biological: TBio-4101

Other Names:

TIL, autologous, tumor-reactive, T-cell product

Drug: Pembrolizumab

Pembrolizumab will be administered after TIL infusion and continue every 3 weeks for up to 2 years.

Other Names:

Keytruda

Outcome Measures

Primary Outcome Measures

Safety and tolerability [25 months]
The incidence of treatment-emergent adverse events will be tabulated using NCI CTCAE v5.0

Secondary Outcome Measures

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,

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Advanced or metastatic breast carcinoma, colorectal adenocarcinoma, or uveal melanoma 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:

Ischemic heart disease (current or past), or clinically significant atrial or ventricular rhythm abnormality are excluded unless cardiac clearance is received.
Prior cell therapy or organ transplant
Have a primary or acquired immunodeficiency disorders
History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, IL-2, or pembrolizumab, or any of their constituents
LVEF ≤ 45% or NYHA functional classification > 1
FEV1 ≤ 60% of predicted value and DLCO (corrected) < 60% of predicted value
Brain metastasis
Chronic anti-coagulant therapy that cannot either be discontinued or temporarily changed
Additional exclusion criteria exist