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 Arm1: Solid Tumors
CyclophosphamideDose Escalation Arm1: Solid Tumors
FludarabineDose Escalation Arm1: Solid Tumors

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 study is comprised of two parallel Phase 1 Arms (solid tumors and multiple myeloma) and a
      Phase 1a expansion in patients with TnMUC1+ platinum-resistant ovarian cancer.

      The Phase 1 portion of the study is designed to identify the dose and regimen of CART-TnMUC1
      cells that can be safely administered intravenously following the lymphodepletion regimen to
      patients with (1) advanced TnMUC1+ solid tumors or (2) advanced TnMUC1+ multiple myeloma in a
      parallel two-arm Phase 1 dose escalation study. It is anticipated that approximately 40
      patients will enroll in the Phase 1 dose escalation.

      The Phase 1a expansion portion of the study is a single arm study designed to assess the
      preliminary efficacy of CART-TnMUC1 cells administered intravenously following the
      lymphodepletion regimen to patients with TnMUC1+ platinum-resistant ovarian cancer. It is
      anticipated that approximately 40 patients will enroll in the Phase 1a expansion.
    

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 at least three different lines of therapy; NSCLC:
             received standard therapy including both checkpoint inhibition and platinum-based
             chemotherapy; Pancreatic adenocarcinoma: disease progression following at least one
             standard of care systemic chemotherapy; TNBC: disease progression following at least
             one prior systemic anti-cancer therapy regimen; patients with PD-L1-positive disease
             must have received a PD-L1 or PD-1 pathway inhibitor; Ovarian: platinum-resistant and
             must have received at least two lines of therapy for metastatic disease

          -  Evaluable disease as defined by tumor type

          -  TnMUC1+ disease, determined by centrally tested TnMUC1 expression in a prior or
             archival tumor biopsy

          -  Completed prior anti-cancer therapy at least 2 weeks prior to Screening and toxicities
             from any previous therapy must have recovered to grade 1 or 0

          -  Life expectancy greater than 3 months

          -  Serum creatinine ≤ 1.2 mg/dL or calculated creatinine clearance ≥ 60 ml/min (using the
             Cockcroft-Gault formula)

          -  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 ≥ 9 g/dL

          -  Absolute neutrophil count ≥ 1500/μL

          -  Platelet count ≥ 100,000/μL (≥ 30,000/μL if bone marrow plasma cells are ≥ 50% of
             cellularity for myeloma patients)

          -  Absolute lymphocyte count of > 500/μL

        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 20 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, active human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis
             B virus (HBV) infections

          -  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:Phase 1: Dose Identification of CART-TnMUC1
Time Frame:Up to 2 years
Safety Issue:
Description:Incidence of Dose Limiting Toxicity (DLT) in Arm 1 and Arm 2 cohorts

Secondary Outcome Measures

Measure:Safety of CART-TnMUC1
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
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
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)
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)
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 or death
Measure:Preliminary anti-tumor efficacy of CART as assessed by Objective Response Rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:Proportion of patients having a confirmed CR or PR per RECIST v1.1
Measure:Preliminary anti-tumor efficacy of CART as assessed by Clinical Benefit Rate
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)
Time Frame:Up to 2 years
Safety Issue:
Description:DOR as defined by the interval between first documented CR or PR until first documented disease progression or death
Measure:Preliminary anti-tumor efficacy of CART as assessed by Time to Response
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
Measure:Expression of TnMUC1
Time Frame:Up to 15 years
Safety Issue:
Description:Correlation of the expression level of TnMUC1 with efficacy parameters
Measure:Peripheral expansion and persistence of CART-TnMUC1 cells
Time Frame:Up to 15 years
Safety Issue:
Description:Correlation with related efficacy and safety parameters

Details

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

Trial Keywords

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

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