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

Overview

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.

SparkCures ID 1034
Trial Phase Phase 1
Enrollment 80 Patients
NCT Identifier

NCT04025216

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

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

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

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

Pennsylvania

Resources

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