Methods of administering natural killer cells comprising an anti-human epidermal growth factor receptor 2 (her2) chimeric antigen receptor (car)

A method comprising administering NK cells to a patient in need thereof, wherein the NK cells comprise a polynucleotide comprising:

• a) a nucleic acid encoding an anti-human epidermal growth factor receptor 2 (HER2) chimeric antigen receptor (CAR) comprising an extracellular antigen binding domain comprising an anti-HER2 antibody or antigen binding fragment thereof;
• and
• b) a nucleic acid encoding an IL-15,
• wherein the NK cells are administered in a dose comprising 1×105 to 10×108 cells/kg.

A method comprising administering multiple doses of NK cells to a patient in need thereof, wherein the NK cells comprise a polynucleotide comprising:

• a) a nucleic acid encoding an anti-human epidermal growth factor receptor 2 (HER2) chimeric antigen receptor (CAR) comprising an extracellular antigen binding domain comprising an anti-HER2 antibody or antigen binding fragment thereof;
• and
• b) a nucleic acid encoding an IL-15, and
• wherein the doses are administered once every one to sixteen weeks.

A method comprising administering NK cells to a patient in need thereof, wherein the NK cells comprise a polynucleotide comprising:

• a) a nucleic acid encoding an anti-human epidermal growth factor receptor 2 (HER2) chimeric antigen receptor (CAR) comprising an extracellular antigen binding domain comprising an anti-HER2 antibody or antigen binding fragment thereof;
• and
• b) a nucleic acid encoding an IL-15,
• wherein the patient meets one or more of the following criteria:
• (i) the patient has an Eastern Cooperative Oncology Group (ECOG) performance status of from 0 to 4 at the time of treatment:
• (ii) the patient is refractory to or has a recurrence after receiving 1 or more prior systemic therapies:
• (iii) the patient has an oxygen saturation level measured via pulse oximeter of at least 92%:
• (iv) the patient has a left ventricular ejection fraction (LVEF) of at least 50%;
• (v) the patient has an absolute neutrophil count (ANC) of at least 1000/mm3 (1.0×109/L);
• (vi) the patient has a platelet count of at least 75000/mm3 (75×109 /L);
• (vii) the patient's hemoglobin level, with or without prior transfusion, is at least 8.0 g/dL:
• (viii) the patient's creatinine clearance is at least 45 mL/min using the Cockcraft-Gault equation, or mL/min/1.73 m2 as estimated glomerular filtration rate (eGFR) per Modification of Diet in Renal Disease (MDRD) equation:
• (ix) the patient's total serum bilirubin is less than 5 mg/dL:
• or
• (x) the patient's liver transaminases (aspartate aminotransferase/alanine amino transferase/alkaline phosphatase (AST/ALT/ALP)) is less than or equal to 5 times the upper limit of normal (ULN) for the test.

A method comprising administering NK cells to a patient in need thereof, wherein the NK cells comprise a polynucleotide comprising:

• a) a nucleic acid encoding an anti-human epidermal growth factor receptor 2 (HER2) chimeric antigen receptor (CAR) comprising an extracellular antigen binding domain comprising an anti-HER2 antibody or antigen binding fragment thereof;
• and
• b) a nucleic acid encoding an IL-15,
• wherein the patient meets one or more of the following criteria:
• (i) the patient does not have active nervous system metastases:
• (ii) the patient does not have a history or presence of a clinically relevant CNS disorder such as a seizure disorder (e.g., epilepsy), cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome (PRES), or any autoimmune disease with CNS involvement:
• (iii) the patient does not have active human immunodeficiency virus (HIV) infection, e.g., as evidenced by a positive HIV polymerase chain reaction (PCR) test;
• (iv) the patient does not have active HBV or hepatitis C virus (HCV) infection, e.g., based on laboratory testing:
• (v) the patient has a viral HBV load below the institutional limit of quantification (LOQ) and the subject is on stable viral suppressive therapy:
• or
• (vi) the patient has a HCV RNA viral load below the institutional LOQ and has completed curative antiviral treatment.

A method comprising administering NK cells to a patient in need thereof, wherein the NK cells comprise a polynucleotide comprising:

• a) a nucleic acid encoding an anti-human epidermal growth factor receptor 2 (HER2) chimeric antigen receptor (CAR) comprising an extracellular antigen binding domain comprising an anti-HER2 antibody or antigen binding fragment thereof;
• and
• b) a nucleic acid encoding an IL-15,
• wherein the patient meets one or more of the following criteria:
• (i) the patient is diagnosed with or has been diagnosed with a HER2+ cancer with an IHC score of 2+;
• (ii) the patient has a cancer that is not HER2-addicted, but shows some degree of HER2-expression:
• (iii) the patient is diagnosed with or has been diagnosed with a HER2-low cancer:
• (iv) the patient is diagnosed with or has been diagnosed with a HER2-low cancer with a HER2 expression classification of score 1+ or 2+;
• (v) the patient is diagnosed with or has been diagnosed with a HER2-low cancer without HER2 amplification;
• (vi) the patient has a cancer comprising a HER2 activating mutation;
• or
• (vii) the patient has been diagnosed with a HER2 expressing cancer that is IHC 1+ or IHC 2+/ISH− and is refractory to or has a recurrence after receiving previous treatment.