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A Study of CART-TnMUC1 in Patients With TnMUC1-Positive Advanced Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04025216
Recruitment Status : Recruiting
First Posted : July 18, 2019
Last Update Posted : April 27, 2022
Sponsor:
Information provided by (Responsible Party):
Tmunity Therapeutics

Brief Summary:
Multi-center, open-label, first in human Phase 1 study of the safety, tolerability, feasibility, and preliminary efficacy of the administration of genetically modified autologous T cells (CART-TnMUC1 cells) engineered to express a chimeric antigen receptor (CAR) capable of recognizing the tumor antigen, TnMUC1 and activating the T cell (CART- TnMUC1 cells).

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Ovarian Cancer Fallopian Tube Cancer Triple Negative Breast Cancer Multiple Myeloma Pancreatic Ductal Adenocarcinoma Biological: CART-TnMUC1 Drug: Cyclophosphamide Drug: Fludarabine Phase 1

Detailed Description:

The Dose Escalation phase of the study is designed to identify the dose and regimen of CART-TnMUC1 cells that can be safely administered intravenously following the lymphodepletion (LD) regimen to patients with (1) advanced TnMUC1+ solid tumors (triple negative breast cancer, epithelial ovarian cancer, pancreatic cancer, and non-small cell lung cancer) and (2) advanced TnMUC1+ multiple myeloma in a parallel two-arm dose escalation study. The Dose Escalation phase is anticipated to enroll approximately 40 patients.

The Expansion phase of the study is designed to assess the preliminary efficacy of CART-TnMUC1 cells administered intravenously to patients with TnMUC1+ solid tumors. The Expansion phase is anticipated to enroll approximately 72 patients (18 patients per each tumor indication).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Parallel arms with sequential dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label, Multi-Center First in Human Study of TnMUC1-Targeted Genetically-Modified Chimeric Antigen Receptor T Cells in Patients With Advanced TnMUC1-Positive Solid Tumors and Multiple Myeloma
Actual Study Start Date : October 10, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : October 31, 2036


Arm Intervention/treatment
Experimental: Dose Escalation Arm1: Solid Tumors
Intravenous CART-TnMUC1 cells for patients with TnMUC1+ treatment-resistant ovarian cancer (including cancers of the fallopian tube), pancreatic ductal adenocarcinoma, hormone receptor (HR)-negative and human epidermal growth factor receptor 2 (HER2)-negative (triple negative) breast cancer and non-small cell lung cancer
Biological: CART-TnMUC1
Single intravenous administration of genetically modified autologous T cells engineered to express a TnMUC1-Targeted Genetically-Modified Chimeric Antigen (CAR)

Drug: Cyclophosphamide
Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-TnMUC1

Drug: Fludarabine
Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-TnMUC1

Experimental: Dose Escalation Arm 2: Multiple Myeloma
Intravenous CART-TnMUC1 cells for patients with TnMUC1+ relapsed/refractory multiple myeloma
Biological: CART-TnMUC1
Single intravenous administration of genetically modified autologous T cells engineered to express a TnMUC1-Targeted Genetically-Modified Chimeric Antigen (CAR)

Drug: Cyclophosphamide
Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-TnMUC1

Drug: Fludarabine
Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-TnMUC1




Primary Outcome Measures :
  1. Dose Escalation: Dose Identification of CART-TnMUC1 [ Time Frame: Up to 2 years ]
    Incidence of Dose Limiting Toxicity (DLT) in solid tumors and multiple myeloma

  2. Cohort Expansion: Objective Response in solid tumors [ Time Frame: Up to 2 years ]
    Proportion of patients having a confirmed Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1


Secondary Outcome Measures :
  1. Safety of CART-TnMUC1 in solid tumors and multiple myeloma [ Time Frame: Up to 2 years ]
    Percentage of patients experiencing adverse events (AEs), including serious and severe AEs overall, by dose level, and by severity Grade

  2. Tolerability of CART-TnMUC1 in solid tumors and multiple myeloma [ Time Frame: Up to 2 years ]
    Frequency of treatment emergent AEs, frequency of clinical changes from baseline in vital signs, changes in electrocardiogram, and hematology and chemistry laboratory shifts from baseline

  3. Feasibility of CART-TnMUC1 in solid tumors and multiple myeloma [ Time Frame: Up to 2 years ]
    Proportion of enrolled patients who did not receive CART-TnMUC1 cells

  4. Preliminary anti-tumor efficacy of CART as assessed by Overall Survival (OS) in solid tumors and multiple myeloma [ Time Frame: Up to 2 years ]
    OS as defined by the interval between CART-TnMUC1 cell infusion and date of death by any cause

  5. Preliminary anti-tumor efficacy of CART as assessed by Progression Free Survival (PFS) in solid tumors [ Time Frame: Up to 2 years ]
    PFS as defined by the interval between CART-TnMUC1 cell infusion and date of disease progression by RECIST v1.1 or death in solid tumors and by International Myeloma Working Group (IMWG) criteria in multiple myeloma

  6. Preliminary anti-tumor efficacy of CART as assessed by Objective Response Rate (ORR) in solid tumors and multiple myeloma [ Time Frame: Up to 2 years ]
    Proportion of patients having a confirmed CR or PR per RECIST v1.1 in solid tumors and IMWG criteria (PR, Very Good PR, CR, Stringent CR) in multiple myeloma

  7. Preliminary anti-tumor efficacy of CART as assessed by Clinical Benefit Rate in solid tumors [ Time Frame: Up to 2 years ]
    Proportion of patients having a confirmed CR, PR, or Stable Disease (SD) per RECIST v1.1

  8. Preliminary anti-tumor efficacy of CART as assessed by Duration of Response (DOR) in solid tumors and multiple myeloma [ Time Frame: Up to 2 years ]
    DOR as defined by the interval of first documented response until first documented disease progression or death in solid tumors and multiple myeloma

  9. Preliminary anti-tumor efficacy of CART as assessed by Time to Response (TTR) in solid tumors and multiple myeloma [ Time Frame: Up to 2 years ]
    Time to Response as defined by the interval between CART-TnMUC1 cell infusion and first documented CR or PR per RECIST v1.1 in solid tumors and IMWG criteria in multiple myeloma

  10. Preliminary anti-tumor efficacy of CART as assessed by Time to Progression (TTP) in multiple myeloma [ Time Frame: Up to 2 years ]
    Time to Progression as defined by the interval between CART-TnMUC1 cell infusion and first documented progression or death due to disease per RECIST v1.1 in solid tumors and IMWG criteria in multiple myeloma

  11. Preliminary anti-tumor efficacy of CART as assessed by Minimal Residual Disease (MRD) in multiple myeloma [ Time Frame: Up to 2 years ]
    Defined by MRD-negative rate per IMWG criteria

  12. Peripheral expansion and persistence of CART-TnMUC1 cells in solid tumors and multiple myeloma [ Time Frame: Up to 15 years ]
    Defined as quantitative polymerase chain reaction (qPCR) documenting loss of CART cells



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Confirmed diagnosis of metastatic treatment-resistant ovarian cancer (including cancers of the fallopian tube), pancreatic adenocarcinoma, hormone receptor (HR)-negative and HER2-negative (triple negative) breast cancer (TNBC) or non-small cell lung cancer (NSCLC), or relapsed/refractory multiple myeloma
  • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
  • Prior therapies as defined by tumor type:

    • Multiple myeloma: relapsed or refractory disease previously treated with or intolerant to at least three different lines of therapy that contained at least one of the following drug classes: proteasome inhibitor, an immune modulatory drug, alkylators, CD38 monoclonal antibody and glucocorticoids. Patients must be at least 90 days since autologous stem cell transplant
    • NSCLC: i.) Patients without driver mutations must have received standard therapy, including both checkpoint inhibition and platinum-based chemotherapy or be intolerant of these standard therapies ii.) Patients with driver mutations must have received or be intolerant to prior targeted therapy directed at the specific identified mutations in addition to the standard chemotherapy classes
    • Pancreatic adenocarcinoma: disease progression following at least one standard of care systemic chemotherapy for metastatic or unresectable disease or be intolerant of these standard therapies
    • TNBC: ER and/or PR < or =10%, HER2 negative and experienced disease progression following at least one prior systemic anti-cancer therapy regimen as part of their treatment for management of metastatic breast cancer or be intolerant to these standard therapies
    • Ovarian: platinum-resistant (progression of disease by either CA-125, clinical or radiographic assessment within 6 months of last platinum-based chemotherapy ) and must have received at least two prior lines of therapy for metastatic ovarian cancer, including at least one prior line of therapy including a platinum-containing regimen or be intolerant of these standard therapies
  • Evaluable disease as defined by tumor type
  • TnMUC1+ disease, determined by centrally tested TnMUC1 expression in a prior or archival tumor biopsy
  • Toxicities from any previous therapy must have recovered to Grade 1 or baseline
  • Estimated estimated glomerular filtration rate ≥ 60 m/min by Modification of Diet in Renal Disease criteria
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x upper institutional limit of normal with the following exception: Patients with known hepatic metastases, AST or ALT ≤ 3 x upper institutional limit of normal
  • Serum total bilirubin < 1.5 mg/dL with the following exception: patients with known Gilbert's disease, serum total bilirubin < 3 mg/dL
  • Serum albumin ≥ 3.0 g/dL (solid tumor patients in Arm 1 and Phase 1a only, not applicable to patients with multiple myeloma)
  • Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF assessment must have been performed within 6 months of treatment start
  • Hemoglobin ≥ 8 g/dL
  • Absolute neutrophil count ≥ 1000/μL
  • Platelet count ≥ 75,000/μL (for Multiple Myeloma patients with bone marrow plasma cells ≥ 50% of cellularity: ≥ 30,000/μL)
  • Patients of reproductive potential agree to use approved contraceptive methods per protocol

Key Exclusion Criteria:

  • Active invasive cancer other than the proposed cancers included in the study
  • Current treatment with systemic high-dose corticosteroids (defined as a dose greater than the equivalent of prednisone 10 mg/day)
  • Active autoimmune disease (including connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease or multiple sclerosis) or have a history of severe autoimmune disease requiring prolonged immunosuppressive therapy (any immunosuppressive therapy should have been stopped within 6 weeks prior to screening visit)
  • Current human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) infections
  • Other active or uncontrolled medical or psychiatric condition that would preclude participation in the opinion of the Sponsor or Principal Investigator
  • Prior allogeneic stem cell transplant
  • Active and untreated central nervous system (CNS) malignancy
  • History of severe infusion reaction to monoclonal antibodies or biological therapies, or to study product excipients that would preclude the patient safely receiving CART-TnMUC1 cells
  • Active or recent (within the past 6 months prior to apheresis) cardiovascular disease, defined as (1) New York Heart Association (NYHA) Class III or IV heart failure, (2) unstable angina or (3) a history of recent (within 6 months) myocardial infarction or sustained (> 30 second) ventricular tachyarrhythmias, or (4) cerebrovascular accident
  • Have inadequate venous access for or contraindications for the apheresis procedure
  • Pregnant or breastfeeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04025216


Contacts
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Contact: Karen Chagin, MD 215-966-1472 clinicaltrials@tmunity.com

Locations
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United States, Arizona
Mayo Clinic of Arizona Recruiting
Phoenix, Arizona, United States, 85054
Contact: Clinical Trials Office    855-776-0015    cancertrials@mayo.edu   
Principal Investigator: Januario E Castro, MD         
United States, California
The Angeles Clinic and Research Institute Recruiting
Los Angeles, California, United States, 90025
Contact: Saba Mukarram    310-231-2181    smukarram@theangelesclinic.org   
Principal Investigator: Omid Hamid, MD         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33637
Contact: Dragana Lakic    813-745-6699    dragana.lakic@moffitt.org   
Principal Investigator: Ben Creelan, MD         
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Michael Bishop, MD    855-702-8222    cancerclinicaltrials@bsd.uchicago.edu   
Principal Investigator: Michael Bishop, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Nic Perry    314-273-2831    nperry@wustl.edu   
Principal Investigator: Daniel Morgensztern, MD         
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Alfred Garfall, MD    855-216-0098    PennCancerTrials@emergingmed.com   
Principal Investigator: Alfred Garfall, MD         
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Allyson Welsch, BS    412-623-6763    welscha2@upmc.edu   
Principal Investigator: Jason Luke, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Melissa Johnson, MD    615-329-7478    DDUreferrals@sarahcannon.com   
Principal Investigator: Melissa Johnson, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: So Jung Hong    713-563-0293    shong7@mdanderson.org   
Principal Investigator: George Blumenschein, MD         
United States, Washington
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98195
Contact: SCCA Intake    206-606-1024    hutchdoc@seattlecca.org   
Principal Investigator: Sylvia Lee, MD         
Sponsors and Collaborators
Tmunity Therapeutics
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Responsible Party: Tmunity Therapeutics
ClinicalTrials.gov Identifier: NCT04025216    
Other Study ID Numbers: CART-TnMUC1-01
First Posted: July 18, 2019    Key Record Dates
Last Update Posted: April 27, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tmunity Therapeutics:
Chimeric Antigen Receptor (CAR)
T-cells
TnMUC1
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Triple Negative Breast Neoplasms
Fallopian Tube Neoplasms
Neoplasms by Site
Neoplasms
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Breast Neoplasms
Breast Diseases
Skin Diseases
Fallopian Tube Diseases
Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents