Clinical Trials

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:
    • Patients without driver mutations must have received standard therapy, including both checkpoint inhibition and platinum-based chemotherapy or be intolerant of these standard therapies;
    • 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 ≤ 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.

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:
  • New York Heart Association (NYHA) Class III or IV heart failure;
  • Unstable angina; or
  • 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.