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Clinical Trial 20615

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT04025216

Phase: Phase I
Principal Investigator: Madden, Jeryl

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Study 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


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).


Primary Objectives: Phase 1: Identify the RP2D for further study of CART-TnMUC1 cells that can be administered safely in patients with either TnMUC1 positive refractory solid tumors (Arm 1) or TnMUC1 positive relapsed/refractory multiple myeloma (Arm 2) in combination with the lymphodepletion (LD) chemotherapy regimen. Phase 1a expansion: Estimate the Objective Response Rate (ORR) of patients with TnMUC1+ platinum resistant ovarian cancer treated with CART-TnMUC1 cells and LD chemotherapy regimen. Secondary Objectives (Phase 1 and Phase 1a expansion): - Assess the safety, tolerability and feasibility of CART-TnMUC1+ refractory solid tumors and relapsed/refractory TnMUC1+ multiple myeloma. -Determine the preliminary anti-tumor efficacy of CART-TnMUC1+ refractory solid tumors and relapsed/refractory multiple myeloma with the endpoints of ORR, OS, Duration of Response (DOR), disease control rate (DCR), Time to Response (TTR), progression free survival (PFS), and minimal residual disease status (MRD). -Correlation of the expansion and persistence of CART-TnMUC1 with efficacy parameters. -Correlation of peripheral expansion and persistence of CART-TnMUC1 cells with related efficacy and safety parameters. Exploratory Objectives (Phase 1 and Phase 1a expansion): -Characterize the clinical pharmacology of the CART-TnMUC1 cells with respect to their expansion, persistence, trafficking, effector status and function (eg. cytokine release) within the periphery and the tumor microenvironment. -Evaluate the pattern of tumor markers (e.g., tumor microenvironment [TME] markers of inflammation and immunosuppression) and soluble disease markers (e.g., CA-125, soluble MUC1, CA19.9) with relation to both safety and efficacy endpoints. -Evaluate the pattern of safety and efficacy in patients pre-treated with prior CART therapy. -Evaluate tumor antigen immune escape mechanisms in tumor biopsies and peripheral blood. -Evaluate the development of anti-CAR immune responses. Secondary Long-term Follow-up Objectives (Phase 1 and Phase 1a expansion): -Evaluate the incidence of new malignancies and pre-malignant conditions in all patients. -Evaluate the de novo incidence of or exacerbation of pre-existing neurologic disorders in all patients. -Evaluate the de novo incidence of or exacerbation of prior rheumatologic or other autoimmune disorders. -Evaluate the de novo incidence of or exacerbation of prior hematologic disorders. -Evaluate vector persistence by assessing the detectable TnMUC1 CAR transgene levels in peripheral blood by q-PCR at pre-specified post CART-TnMUC1 infusion time points. -Evaluate patients for the presence of detectable RCL by VSV-G.



Chemotherapy (NOS); Immunotherapy


CART-TnMUC1 (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

Inclusion Criteria

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: (a) 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 (b) NSCLC: i.) Patients without driver mutations must have received standard chemotherapy, 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 (c) 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 (d) TNBC: ER and/or PR > 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 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 > 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: ≥ 30,000/μL)
  • Absolute lymphocyte count of ≥ 500/μL
  • Patients of reproductive potential agree to use approved contraceptive methods per protocol
  • Other criteria may apply

  • Exclusion Criteria

    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
  • Patients who are hepatitis B core antibody positive, hepatitis B surface antigen negative should have quantitative viral load measured.
  • If the viral load is undetectable, the patient will be able to be treated with anti-viral medication (e.g. entecavir) for at least 7 days prior to lymphodepletion until at least 6 months after infusion, and will undergo appropriate viral load and alanine aminotransferase monitoring per the American Society of Clinical Oncology guidelines (Hwang, 2015), the patient will not be excluded. Consultation with a Hepatitis B specialist is recommended. Discussion with Sponsor Medical Monitor is recommended.
  • 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
  • Other exclusions may apply

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