Ensayos clínicos

Inclusion Criteria:

• Patients must be adults at least 18 years of age and sign the main study informed consent form.
• Patients must have a confirmed diagnosis of metastatic treatment-resistant epithelial 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.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
• Patients must have received or be intolerant to the following prior therapy(ies):
  • NSCLC
  • Patients without driver mutations (e.g., EGFR, ALK, ROS, BRAF, RET) must have received standard therapy, including both checkpoint inhibition (PD-1/PD-L1 directed therapy) 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 chemotherapy classes described above;
  • Pancreatic adenocarcinoma: Patients must have experienced disease progression following at least one standard of care systemic chemotherapy for metastatic or unresectable disease or be intolerant of these standard therapies;
  • Triple-negative Breast cancer (TNBC): Patients must have 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 of these standard therapies;
  • Ovarian cancer: Patients are eligible if considered 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;
  • Multiple myeloma: relapsed or refractory disease previously treated with or be intolerant to at least three different lines of therapy that contained at least one of the following drug classes: proteasome inhibitor, immune modulatory drug (IMiD), alkylators, CD38 monoclonal antibodies and glucocorticoids. Patients must be at least 90 days since autologous stem cell transplant, if performed.
• Patients must have evaluable disease, qualified as to the following:
  • Solid tumors: Patients must have measurable disease as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v.1.1, [Eisenhauer et al, 2009]).
  • Multiple Myeloma i. Patients must have measurable disease per IMWG criteria on study entry, which must include at least one of the following:
  • Serum M spike ≥ 0.5 g/dL;
  • 24-hour urine M-spike ≥ 200 mg 3. Involved serum free light chain (FLC) ≥ 50 mg/L with abnormal ratio.
  • Note: Patients with IgA myeloma in whom serum protein electrophoresis is deemed unreliable, due to co-migration of normal serum proteins with the paraprotein in the beta region, may be considered eligible as long as total serum IgA level is elevated above normal range.
• All patients must have TnMUC1+ disease, determined by centrally tested TnMUC1 expression in a prior or archival tumor biopsy. If an archival tumor biopsy sample is not available, then the patient may undergo a biopsy for the purposes of screening eligibility with only non-significant risk biopsy procedures.
• Toxicities from any previous therapy must have recovered to grade 1 or baseline. (Exceptions include stable toxicities as a result of previous therapy such as alopecia, well controlled electrolyte or endocrine abnormalities, peripheral neuropathy, and vitiligo).
• Adequate vital organ function as defined by:
  • estimated Glomerular Filtration Rate (eGFR) ≥ 60 ml/min by Modification of Diet in Renal Disease criteria;
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 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;
  • Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF assessment must have been performed within 6 months of treatment start.
• Adequate hematologic reserve as defined by:
  • Hemoglobin ≥ 8 g/dL;
  • Absolute neutrophil count ≥ 1000/μL;
  • Platelet count ≥ 75,000/μL (≥ 30,000/μL if bone marrow plasma cells are ≥ 50% of cellularity for myeloma patients).
  • Note: Patients must not have had transfusion (pRBC or PLTs) to maintain hematologic parameters or received growth factors within 2 weeks prior to screening labs.
• 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). Low-dose physiologic replacement therapy with corticosteroids equivalent to prednisone 10 mg/day or lower is acceptable.
• 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 HIV, HCV, HBV infections. Viral testing at Screening is required in all patients to rule out subclinical 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.
• 7. Active and untreated central nervous system (CNS) malignancy. Treated lesions may be considered inactive if they are stable for at least 1 month following definitive treatment. Patient must not require corticosteroid therapy or anti-epileptic medications for the management of brain metastases. Prophylactic epileptic medications are permitted.
• History of severe infusion reaction to monoclonal antibodies or biological therapies, or to study product excipients (e.g., human serum albumin, dimethyl sulfoxide (DMSO), dextran 40) that would preclude the patient safely receiving CARTTnMUC1 cells.
• Active or recent (within the past 6 months prior to apheresis) cardiovascular disease, defined as:
  • New York Heart Association (NYHA) Class III or IV heart failure;
  • unstable angina;
  • a history of recent (within 6 months) myocardial infarction or sustained (> 30 second) ventricular tachyarrhythmias; or
  • cerebrovascular accident.
• Have inadequate venous access for or contraindications for the apheresis procedure. Central venous access is acceptable.
• Pregnant or breastfeeding women.