Mesothelin-Specific T-Cells (FH-TCR-Tᴍsʟɴ) for the Treatment of Metastatic Pancreatic Ductal Adenocarcinoma

NCT04809766 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: RG1007292NCI-2020-0849610417
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial evaluates the side effects and best dose of mesothelin-specific T-cells (FH-TCR-Tᴍsʟɴ) in treating patients with pancreatic ductal adenocarcinoma that has spread to other places in the body (metastatic). Chemotherapy drugs, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading, and may help increase the efficacy from the infused T cells. FH-TCR-Tᴍsʟɴ is an autologous T cell therapy targeting mesothelin, an antigen overexpressed by pancreatic cancer cells. T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize mesothelin, a protein on the surface and inside tumor cells. These mesothelin-specific T cells may help the body's immune system identify and kill mesothelin+ tumor cells. Giving chemotherapy with FH-TCR-Tᴍsʟɴ may kill more tumor cells in the treatment of patients with metastatic pancreatic ductal adenocarcinoma.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma; Stage IV Pancreatic Cancer AJCC v8

Keywords

Pancreas

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Toxicity (adverse events) will be recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.

  Up to 4 weeks after the last T cell infusion

• Dose limiting toxicities

  Up to 21 days after each T cell infusion

Secondary Outcomes (6)

• Overall response rate

  Up to 1 year after the last T cell infusion

• Progression free survival

  Up to 1 year after the last T cell infusion

• Overall survival

  Up to 1 year after the last T cell infusion

• Feasibility of reproducibly generating FH-TCR-Tᴍsʟɴ from autologous patient cells

  Through last T cell infusion

• Stable disease (SD) rate

  Up to 1 year after the last T cell infusion

Study Arms (2)

Cohorts I, II, and III (FH-TCR Tᴍsʟɴ)

EXPERIMENTAL

LYMPHODEPLETION CHEMOTHERAPY: Patients receive cyclophosphamide IV and fludarabine IV on days -5, -4 and -3 or may optionally receive bendamustine IV on days -4 and -3 prior to the 1st T cell infusion. T-CELL THERAPY: Patients receive FH-TCR-Tᴍsʟɴ IV over 60-120 minutes on days 0, 21, and 42 in the absence of disease progression or unacceptable toxicity.

Biological: Autologous Mesothelin-specific TCR-T Cells; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Bendamustine

Cohort IV (FH-TCR Tᴍsʟɴ) (Discontinued with amendment 3/28/23)

EXPERIMENTAL

LYMPHODEPLETION CHEMOTHERAPY: Patients receive cyclophosphamide IV and fludarabine IV on days -3 to -1. T-CELL THERAPY: Patients receive FH-TCR-Tᴍsʟɴ IV over 60-120 minutes on days 0, 21, and 42 in the absence of disease progression or unacceptable toxicity.

Biological: Autologous Mesothelin-specific TCR-T Cells; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Autologous Mesothelin-specific TCR-T Cells BIOLOGICAL

Receive FH-TCR Tᴍsʟɴ IV

Cohort IV (FH-TCR Tᴍsʟɴ) (Discontinued with amendment 3/28/23); Cohorts I, II, and III (FH-TCR Tᴍsʟɴ)

Cyclophosphamide DRUG

Given IV

Also known as: Endoxan, Cytoxan, Neosar, Procytox, Revimmune, Cytophosphane, 6055-19-2, Asta B 518, WR-138719

Cohort IV (FH-TCR Tᴍsʟɴ) (Discontinued with amendment 3/28/23); Cohorts I, II, and III (FH-TCR Tᴍsʟɴ)

Fludarabine DRUG

Given IV

Also known as: Fluradosa, 21679-14-1

Cohort IV (FH-TCR Tᴍsʟɴ) (Discontinued with amendment 3/28/23); Cohorts I, II, and III (FH-TCR Tᴍsʟɴ)

Bendamustine DRUG

Given IV

Also known as: SDX-105, 16506-27-7

Cohorts I, II, and III (FH-TCR Tᴍsʟɴ)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• LEUKAPHERESIS: Tissue confirmation of pancreatic ductal adenocarcinoma and expression of mesothelin (MSLN): Participants must have metastatic disease. Confirmation of diagnosis must be or have been performed by internal pathology review of archival, initial or subsequent biopsy or other pathologic material at Fred Hutchinson Cancer Research Center (Fred Hutch)/University of Washington (UW). Baseline tissue will be stained by immunohistochemistry (IHC) to confirm MSLN expression
• LEUKAPHERESIS: Measurable disease by RECIST 1.1 criteria: Participants must have measurable disease. Baseline imaging (for example diagnostic computed tomography \[CT\] chest/abdomen/pelvis) must be obtained within 28 days prior to start of first planned FHMSLN-TCR infusion. Magnetic resonance imaging (MRI) can be substituted for CT in patients unable to have CT contrast
• LEUKAPHERESIS: Previous treatment with chemotherapy: Patients may have been previously treated with at least one prior line of systemic therapy for metastatic disease
• LEUKAPHERESIS: Human leukocyte antigen (HLA) type HLA-A\*02:01: Participants must be HLA-A\*02:01 in order for the infused transgenic T cells to recognize antigen-major histocompatibility complex (MHC) complexes on their tumor. HLA typing should be determined though a molecular approach in a clinical laboratory licensed for HLA typing
• LEUKAPHERESIS: Life expectancy must be \> 3 months at trial entry
• LEUKAPHERESIS: 18 years or older
• LEUKAPHERESIS: Capable of understanding and providing a written informed consent
• LEUKAPHERESIS: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• LEUKAPHERESIS: Tumor tissue amenable to safe biopsy and subject willing to undergo serial tumor biopsies at baseline (prior to first T cell infusion), 2-3 weeks after the first T cell infusion (prior to second T cell infusion), and approximately 2 weeks +/- 1 week after the 3rd infusion, if safe and feasible (these windows may vary due to manufacturing or clinical reasons): Should there be no tumor tissue that is accessible for biopsy, patients will still be considered for participation, at discretion of the investigator. Similarly, should an investigator determine that a biopsy cannot be performed safely for clinical reasons, biopsies may be cancelled or rescheduled. For subjects who do not have sufficient T cells for three T cell infusion, a tumor tissue biopsy will be performed at baseline (prior to the 1st T cell infusion), 2-3 weeks after the 1st infusion, and approximately 2 weeks +/- 1 week after the 2nd infusion (if applicable), if safe and feasible.
• LEUKAPHERESIS: Participants must be at least 3 weeks from last systemic treatment for metastatic disease: At least 3 weeks must have passed since any: immunotherapy (for example, T cell infusions, immunomodulatory agents, interleukins, vaccines), small molecule or chemotherapy cancer treatment, other investigational agents. There is no washout period for radiation, as long as the irradiated lesion is not the lesion being evaluated for RECIST measurements on the protocol. Bisphosphonates are permitted but concurrent treatment with RANK-ligand inhibitors (i.e., denosumab) is not permitted within 8 weeks of treatment
• LEUKAPHERESIS: Estimated glomerular filtration rate (eGFR) \> 60 mL/min
• LEUKAPHERESIS: Total bilirubin (bili) =\< 1.5 X ULN. Patients with suspected Gilbert syndrome may be included if total bili \> 3 mg/dL but no other evidence of hepatic dysfunction
• LEUKAPHERESIS: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 x ULN
• LEUKAPHERESIS: =\< grade 1 dyspnea and oxygen saturation (SaO2) \>= 92% on ambient air. If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, patients with forced expiratory volume in 1 second (FEVI) \>= 50% of predicted and carbon monoxide diffusing capability test (DLCO) (corrected) of \>= 40% of predicted will be eligible
• LEUKAPHERESIS: Patients \>= 60 years of age are required to have left ventricular ejection fraction (LVEF) evaluation performed within 1 year prior to study treatment. LVEF may be established with echocardiogram or multigated acquisition scan (MUGA) scan, and left ejection fraction must be \>= 35%. Cardiac evaluation for other patients is at the discretion of the treating physician

You may not qualify if:

• LEUKAPHERESIS: Expression of HLA B\*1302: Participants will be excluded due to the risk of alloreactivity to this allele
• LEUKAPHERESIS: Pregnancy or lactation
• LEUKAPHERESIS: Active autoimmune disease: Patients with active autoimmune disease requiring immunosuppressive therapy are excluded. Case by case exemptions are possible with approval by principal investigator (PI)
• LEUKAPHERESIS: Prior solid organ transplant or allogeneic hematopoietic stem cell transplant
• LEUKAPHERESIS: Corticosteroid therapy at a dose equivalent of \> 0.5 mg/kg of prednisone per day
• LEUKAPHERESIS: Concurrent use of other investigational anti-cancer agents
• LEUKAPHERESIS: Active uncontrolled infection: Human immunodeficiency virus (HIV) positive participants on highly active antiretroviral therapy (HAART) with a CD4 count \> 500 cells/mm\^3 are considered controlled, as are individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have hepatitis well controlled on medication
• LEUKAPHERESIS: Uncontrolled concurrent illness: Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• LEUKAPHERESIS: Active treatment for prior immune related adverse event to any immunotherapy: Participants receiving ongoing treatment for prior serious immune-related adverse events are excluded, with exception of hormone supplementation or corticosteroid therapy at equivalent of up to 0.5 mg/kg prednisone per day, unless otherwise approved by PI
• LEUKAPHERESIS: Significant underlying neurologic disease: Study participants must not have significant active underlying neurologic disease, unless approved by PI. Neuropathy related to diabetes or prior chemotherapy is acceptable
• LEUKAPHERESIS: Uncontrolled pleural effusion, pericardia) effusion, or ascites requiring repeated drainage more than once every 28 days
• LEUKAPHERESIS: Other medical, social, or psychiatric factor that interferes with medical appropriateness and/or ability to comply with study, as determined by the PI
• TREATMENT: Corticosteroid therapy at a dose equivalent of \> 0.5 mg/kg of prednisone per day
• TREATMENT: Concurrent use of other investigational anti-cancer agents
• TREATMENT: Uncontrolled concurrent illness: Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Lonza Walkersville, Inc.: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Cyclophosphamide; fludarabine; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Butyrates; Acids, Acyclic; Carboxylic Acids; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Elena G. Chiorean

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2021
• First Posted: March 22, 2021
• Study Start: December 14, 2021
• Primary Completion: October 24, 2024
• Study Completion: January 15, 2025
• Last Updated: April 20, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)