A Phase 2 Multicenter Study Evaluating the Efficacy and Safety of IPI-504 in Combination With Trastuzumab in Patients With Pretreated, Locally Advanced or Metastatic Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer

Inclusion Criteria:

- Locally advanced/metastatic breast cancer.

- HER2-expressing primary or metastatic tumor

- Two prior regimens with HER2. Trastuzumab must have been given. No limit to prior
therapies

- Measurable disease with RECIST 1.1

- Clinical progression

- LVEF WNL

- ECOG 0 or 1

- Last dose of chemotherapy, radiotherapy, surgery, ablative therapy, tyrosine kinase
inhibitor, ≥2 weeks

- Administration of biological therapy ≥4 weeks

- Last dose of trastuzumab must be ≥1, or ≥3 weeks prior to start, if previously
administered on an every 3 week schedule.

- Resolution of toxic effects to baseline or Grade 1, except alopecia (NCI CTCAE
Version 3.0

- Organ and marrow function:

- Hemoglobin ≥8.0 g/dL

- ANC ≥1200/µL

- Platelets ≥75,000 /µL

- ALT and AST ≤ 1.5 x ULN

- Alkaline phosphatase ≤2.5 x ULN, or ≤3.0 x ULN if secondary to liver metastases.

- Serum bilirubin WNL

- Serum albumin ≥3.0 g/dL

- PT, PTT ≤1.5 x ULN

- Serum creatinine ≤1.5 x ULN

- Negative pregnancy test

Exclusion Criteria:

- Prior treatment with Hsp90 inhibitor.

- Grade 4 AE secondary to trastuzumab. Grade 3/4 infusion reactions or Grade 3/4
symptomatic heart failure

- Medication/food that is a CYP3A inhibitor or inducer.

- Hx 6 months: cardiac disease - acute coronary syndrome or unstable angina,
symptomatic congestive heart failure, uncontrolled hypertension, cirrhotic liver
disease, cerebrovascular accident or significant co-morbid condition

- Grade 3 or 4 hemorrhagic event within 6 months.

- HIV positivity

- Baseline QT corrected, QTcF >470 ms

- Sinus bradycardia <50 bpm Secondary to pharmacologic therapy may enroll if stopping
therapy normalizes heart rate.

- Malignancies within 3 years other than non-melanomatous skin cancers,
non-muscle-invasive bladder cancer and carcinoma in situ of cervix.

- Active keratitis or keratoconjunctivitis

- Active brain metastasis (e.g., requiring therapy with steroids or radiation therapy;
or with intracranial progression 4 weeks after the completion of radiation therapy)
uncontrolled seizure disorder, ongoing spinal cord compression, or carcinomatous
meningitis. If clinically stable brain metastasis (previously treated or
untreated)are present pt is eligible.