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

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 that contained at least one of the following drug classes: proteasome inhibitor, an immune modulatory drug, alkylators, CD38 monoclonal antibody and glucocorticoids. Patients must be at 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 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 chemotherapy 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 \< or =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 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 plasma cells ≥ 50% of cellularity: ≥ 30,000/μL)
• •Patients of reproductive potential agree to use approved contraceptive methods per protocol