The HEROINE-Breast01 study is a Phase I/II clinical study of a new investigational agent,
AIP-303 to help patients with metastatic or unresectable HER2-positive breast cancer and for
women with previously treated HER2 positive breast cancer who have gone through at least two
prior lines of treatment and received other HER-2-targeted drugs, Trastuzumab or
Ado-Trastuzumab and chemotherapy as part of earlier treatments and who have progressed on one
or more available therapies. AIP-303 may help slow down tumor growth and this might improve
outcomes and quality-of-life for these patients.
This is a prospective, Phase I/II, multi-center, open-label study in a total of 150 subjects
with HER2 Positive Breast cancer tumors. Eligible participants will undergo baseline
assessments at enrollment. Study participants be administered therapeutic doses of AIP-303 up
to four treatments spaced 8 weeks apart and a CT scan immediately after. An AIP 301 Ga-68
PET/CT scan will be performed four weeks before and four weeks after the initial dose of the
AIP-303. An IEC will review the protocol and any amendments and advertisements used for
recruitment. The IEC will review the patient information sheet and the informed consent form,
their updates (if any), and any written materials given to the patients. A list of all IECs
to which the protocol has been submitted and the name of the committee chairmen will be
included in the clinical trial report.
- • Patients with HER2+ metastatic solid tumors (may be 3+ by immunohistochemistry or
with evidence of gene amplification (>2.0) by fluorescence in situ hybridization
- 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
- Able to provide informed consent. Karnofsky score greater than 50
- Females of childbearing potential must have a negative pregnancy test at
- 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
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
- • Must not have HER2+ Brain Mets
- Serious underlying disease other than HER2+ breast cancer in the opinion of the
- 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
- 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
- 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
- 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