Clinical Trials /

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

NCT04025216

Description:

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).

Related Conditions:
  • Breast Carcinoma
  • Fallopian Tube Carcinoma
  • Multiple Myeloma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of CART-TnMUC1 in Patients With TnMUC1-Positive Advanced Cancers
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CART-TnMUC1-01
  • NCT ID: NCT04025216

Conditions

  • Non-Small Cell Lung Cancer
  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Triple Negative Breast Cancer
  • Multiple Myeloma
  • Pancreatic Ductal Adenocarcinoma

Interventions

DrugSynonymsArms
CART-TnMUC1Dose Escalation Arm 2: Multiple Myeloma
CyclophosphamideDose Escalation Arm 2: Multiple Myeloma
FludarabineDose Escalation Arm 2: Multiple Myeloma

Purpose

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).

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).
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Arm1: Solid TumorsExperimentalIntravenous 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
  • CART-TnMUC1
  • Cyclophosphamide
  • Fludarabine
Dose Escalation Arm 2: Multiple MyelomaExperimentalIntravenous CART-TnMUC1 cells for patients with TnMUC1+ relapsed/refractory multiple myeloma
  • CART-TnMUC1
  • Cyclophosphamide
  • Fludarabine

Eligibility 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 and be relapse/refractor
                  or intolerant to a proteasome inhibitor, an immune modulatory drug, and a CD38
                  monoclonal antibody. 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 therapy 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 8 weeks of screening

          -  Hemoglobin ≥ 8 g/dL

          -  Absolute neutrophil count ≥ 1000/μL

          -  Platelet count ≥ 75,000/μL (for Multiple Myeloma patients: ≥ 30,000/μL)

          -  Absolute lymphocyte count of ≥ 500/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) cardiac 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

          -  Have inadequate venous access for or contraindications for the apheresis procedure

          -  Pregnant or breastfeeding women
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Escalation: Dose Identification of CART-TnMUC1
Time Frame:Up to 2 years
Safety Issue:
Description:Incidence of Dose Limiting Toxicity (DLT) in solid tumors and multiple myeloma

Secondary Outcome Measures

Measure:Safety of CART-TnMUC1 in solid tumors and multiple myeloma
Time Frame:Up to 2 years
Safety Issue:
Description:Percentage of patients experiencing adverse events (AEs), including serious and severe AEs overall, by dose level, and by severity Grade
Measure:Tolerability of CART-TnMUC1 in solid tumors and multiple myeloma
Time Frame:Up to 2 years
Safety Issue:
Description: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
Measure:Feasibility of CART-TnMUC1 in solid tumors and multiple myeloma
Time Frame:Up to 2 years
Safety Issue:
Description:Proportion of enrolled patients who did not receive CART-TnMUC1 cells
Measure:Preliminary anti-tumor efficacy of CART as assessed by Overall Survival (OS) in solid tumors and multiple myeloma
Time Frame:Up to 2 years
Safety Issue:
Description:OS as defined by the interval between CART-TnMUC1 cell infusion and date of death by any cause
Measure:Preliminary anti-tumor efficacy of CART as assessed by Progression Free Survival (PFS) in solid tumors
Time Frame:Up to 2 years
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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
Measure:Preliminary anti-tumor efficacy of CART as assessed by Clinical Benefit Rate in solid tumors
Time Frame:Up to 2 years
Safety Issue:
Description:Proportion of patients having a confirmed CR, PR, or Stable Disease (SD) per RECIST v1.1
Measure: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
Safety Issue:
Description:DOR as defined by the interval of first documented response until first documented disease progression or death in solid tumors and multiple myeloma
Measure: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
Safety Issue:
Description: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
Measure:Preliminary anti-tumor efficacy of CART as assessed by Time to Progression (TTP) in multiple myeloma
Time Frame:Up to 2 years
Safety Issue:
Description: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
Measure:Preliminary anti-tumor efficacy of CART as assessed by Minimal Residual Disease (MRD) in multiple myeloma
Time Frame:Up to 2 years
Safety Issue:
Description:Defined by MRD-negative rate per IMWG criteria
Measure:Peripheral expansion and persistence of CART-TnMUC1 cells in solid tumors and multiple myeloma
Time Frame:Up to 15 years
Safety Issue:
Description:Defined as quantitative polymerase chain reaction (qPCR) documenting loss of CART cells

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tmunity Therapeutics

Trial Keywords

  • Chimeric Antigen Receptor (CAR)
  • T-cells
  • TnMUC1

Last Updated

February 26, 2021