A Study of AIP-303 in HER2 Positive Breast Cancer and/or Metastatic Breast Cancer Patients (Heroine01)

Inclusion Criteria:

• • Patients with HER2+ metastatic solid tumors (may be 3+ by immunohistochemistry or with evidence of gene amplification (>2.0) by fluorescence in situ hybridization (FISH))

  • Currently experiencing tumor progression on active Trastuzumab, Ado-Trastuzumab/Taxane and/or standard of care.
  • At least 18 years of age
  • The patient is able and willing to comply with the requirements of this trial protocol.
  • Able to provide informed consent. Karnofsky score greater than 50
  • Females of childbearing potential must have a negative pregnancy test at screening/ baseline
  • AIP 301 positive scan define by SUV greater than 10.

  • Adequate organ function, defined as:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
    2. Hemoglobin (Hb) ≥9 g/dl (transfusion or use of EPO is permitted).
    3. Platelets > 100,000/mm3
    4. Creatinine ≤ 1.5 x normal value
    5. AST or ALT ≤ 2.5 x ULN (or ≤5 x ULN in case of liver metastasis)
    6. Alkaline phosphatase ≤2.5 x ULN. Alkaline phosphatase may be more than 2.5 x ULN only in the case of bone metastases, and AST and ALT less than 1.5 x ULN.
    7. Total bilirubin ≤1.5 mg/dl (higher bilirubin levels are permitted if the patient has Gilbert's syndrome).
  • Baseline LVEF ≥50% measured using echocardiogram or equilibrium isotopic ventriculography (MUGA).

Exclusion Criteria:

• • Must not have HER2+ Brain Mets

  • Serious underlying disease other than HER2+ breast cancer in the opinion of the investigator.
  • History of drug addiction within the last 1 year or current drug addiction or use of illicit drugs.
  • Any indication of the regular use of more than 40 grams of alcohol every day.
  • Smokers who smoke more than 10 cigarettes per day.
  • Known concurrent acute or chronic viral hepatitis B or C infection or human immunodeficiency virus (HIV) infection.
  • Presence or history of active tuberculosis (TB) or latent TB infection, defined as 1) a positive QuantiFERON-TB Gold test at Screening, or 2) a positive T-spot test within 4 weeks of visit 3 and evidence of current or previous pulmonary tuberculosis by chest X-ray within 12 weeks of Visit 3.
  • Positive immunoglobulin M antibody titers in the presence of negative immunoglobulin G titers to Epstein-Barr virus (EBV).
  • If clinical suspicion of cytomegalovirus (CMV), cytomegalovirus testing should be undertaken. Subjects with intestinal mucosa biopsy positive for cytomegalovirus at screening are to be excluded.
  • Currently taking any medications other than those allowed per protocol guidelines.
  • Infections (including diverticulitis) requiring treatment with antibiotics, antivirals, or antifungals within 14 days prior to Visit.
  • Serum creatinine >3.0 mg/dL (270 μM/L)
  • Known severe allergy or hypersensitivity to IV radiographic contrast.
  • Use of any other investigational product or device within 30 days prior to dosing or known requirement for any other investigational agent prior to completion of all scheduled study assessments.
  • Patients with a body weight of 400 pounds or more or not able to enter the bore of the PET/CT scanner due to BMI, because of the compromise in image quality
  • Inability to complete the needed investigational and standard-of-care imaging examinations due to other reasons (severe claustrophobia, radiation phobia, etc.)
  • Recognized concurrent active infection
  • Previous Grade 3 or higher allergic reaction to Trastuzumab or Ado-Trastuzumab that resulted in discontinuation of Trastuzumab or Ado-Trastuzumab therapy. Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance.
  • Moderate to severe anemia (hemoglobin <9 g/dL), or thrombocytopenia (platelet count <75,000/μL), or serum creatinine >2 mg/dL.
  • Primary or secondary immunodeficiency including neutropenia (absolute neutrophil count <1500/μL); or lymphopenia (absolute lymphocyte count <500/μL).
  • Hepatic enzyme levels more than 5 times upper limit of normal: Known clinically relevant chronic liver disease.

Impaired hepatic function in the absence of a diagnosis of primary sclerosing cholangitis (serum transaminases >2.5 x upper limit of normal [ULN], alkaline phosphatase >2.5 x ULN, or abnormalities in synthetic liver function tests judged by the investigator to be clinically significant), or a diagnosis of primary sclerosing cholangitis, serum transaminases >3 x ULN, alkaline phosphatase >3 x ULN, or abnormalities in synthetic liver function tests (total bilirubin >1.5 x ULN) judged by the investigator to be clinically significant.

• Received any live (attenuated) vaccines within 30 days prior to Visit.
• Recent treatment with medium-to-high-dose intravenous corticosteroids (methylprednisolone 60 mg/day or hydrocortisone 300 mg/day) within 8 weeks prior to Visit or oral corticosteroids of more than 20 mg prednisone (or equivalent) within 30 days prior to Visit.
• Peptide receptor radionuclide therapy (PRRT) at any time prior to enrolment in the study.
• Receipt of cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 30 days prior to Visit.
• Treatment with therapeutic enema or suppository, other than required for endoscopy preparation, within 14 days prior to the screening endoscopy and during the remainder of the trial.
• Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study