Clinical trial NCT05576077: A Study of TBio-4101 (TIL) and Pembrolizumab in Patients With Advanced Solid Tumors
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Breast Cancer
Colorectal Cancer
Uveal Melanoma
Cutaneous Melanoma
Non-Small Cell Lung Cancer
Head and Neck Squamous Cell Carcinoma
Keywords: MSS-CRC
TIL
Tumor infiltrating lymphocyte
TNBC
HR+ Breast
ER+ Breast
MSI-CRC
personalized medicine
ocular melanoma
Lead sponsor: Turnstone Biologics, Corp.
Sponsor class: INDUSTRY
First posted: 2022-10-12
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients enrolled into a Cohort based on malignancy.
Primary purpose: TREATMENT

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.

Eligibility 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 exclusion criteria exist

Primary outcomes:
measure: Safety and tolerability
timeFrame: 25 months
Secondary outcomes:
measure: Proportion of patients with a response (ORR)
timeFrame: 25 months
measure: Estimated Disease Control Rate (DCR)
timeFrame: 25 months
measure: Estimated Duration of Response (DoR)
timeFrame: 25 months
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny Research Institute
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: Montreal University Hospital Center
state: Quebec
Study officials:
affiliation: Turnstone Biologics, Corp.
name: Ines Verdon, MD
role: STUDY_DIRECTOR
References: