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

Key Inclusion Criteria:

• Confirmed diagnosis of metastatic treatment-resistant ovarian cancer (includingcancers of the fallopian tube), pancreatic adenocarcinoma, hormone receptor (HR)-negative and HER2-negative (triple negative) breast cancer (TNBC) or non-smallcell 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 orintolerant to at least three different lines of therapy that contained at leastone of the following drug classes: proteasome inhibitor, an immune modulatorydrug, alkylators, CD38 monoclonal antibody and glucocorticoids. Patients must beat 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 beintolerant of these standard therapies ii.) Patients with driver mutations musthave received or be intolerant to prior targeted therapy directed at the specificidentified mutations in addition to the standard chemotherapy classes
• Pancreatic adenocarcinoma: disease progression following at least one standard ofcare systemic chemotherapy for metastatic or unresectable disease or beintolerant of these standard therapies
• TNBC: ER and/or PR < or =10%, HER2 negative and experienced disease progressionfollowing at least one prior systemic anti-cancer therapy regimen as part oftheir treatment for management of metastatic breast cancer or be intolerant tothese standard therapies
• Ovarian: platinum-resistant (progression of disease by either CA-125, clinical orradiographic assessment within 6 months of last platinum-based chemotherapy ) andmust have received at least two prior lines of therapy for metastatic ovariancancer, including at least one prior line of therapy including aplatinum-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 orarchival 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 inRenal Disease criteria
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x upperinstitutional limit of normal with the following exception: Patients with knownhepatic metastases, AST or ALT ≤ 3 x upper institutional limit of normal
• Serum total bilirubin < 1.5 mg/dL with the following exception: patients with knownGilbert's disease, serum total bilirubin < 3 mg/dL
• Serum albumin ≥ 3.0 g/dL (solid tumor patients in Arm 1 and Phase 1a only, notapplicable to patients with multiple myeloma)
• Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF assessment must have beenperformed within 6 months of treatment start
• Hemoglobin ≥ 8 g/dL
• Absolute neutrophil count ≥ 1000/μL
• Platelet count ≥ 75,000/μL (for Multiple Myeloma patients with bone marrow plasmacells ≥ 50% of cellularity: ≥ 30,000/μL)
• Patients of reproductive potential agree to use approved contraceptive methods perprotocol

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 greaterthan 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 severeautoimmune disease requiring prolonged immunosuppressive therapy (anyimmunosuppressive therapy should have been stopped within 6 weeks prior to screeningvisit)
• Current human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) infections
• Other active or uncontrolled medical or psychiatric condition that would precludeparticipation 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 receivingCART-TnMUC1 cells
• Active or recent (within the past 6 months prior to apheresis) cardiovascular 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 orsustained (> 30 second) ventricular tachyarrhythmias, or (4) cerebrovascular accident
• Have inadequate venous access for or contraindications for the apheresis procedure
• Pregnant or breastfeeding women