ZW25 in Women With Endometrial Cancers

Inclusion Criteria

• Patients must be enrolled or agree to consent to the companion genomic profiling study MSKCC IRB# 12-245 Part A. Results are not required prior to initiating treatment on protocol, unless patients do not have other test results by IHC or FISH confirming HER2 overexpression.
• Patients must have recurrent or persistent HER2 overexpressing endometrial cancer or endometrial carcinosarcoma. HER2 overexpression is defined as 3+ by IHC or 2+ with gene amplification by FISH (HER2/CEP17 ratio ≥ 2) or HER2 amplified (fold change ≥ 2) on MSK IMPACT.
• Histologic documentation of diagnosis of endometrial carcinoma or carcinosarcoma is required.
• Age ≥ 18 years
• Patients must have had at least one but no more than two prior chemotherapeutic regimens for management of endometrial carcinoma (including neo-adjuvant and/or adjuvant chemotherapy). Initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen. Prior hormonal therapy will not count as a prior regimen. Prior treatment with trastuzumab is allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• LVEF ≥ 50% on baseline screening ECHO.
• Resolution of adverse effects of recent surgery, radiotherapy, or chemotherapy to Grade ≤ 1 prior to first study treatment (with the exception of alopecia or clinically insignificant laboratory values).
• Patients must have measurable disease. Measurable disease is defined by RECIST (version 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each non-nodal lesion must be 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or 20 mm when measured by chest x-ray. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI.
• No active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection).
• All patients must consent to mandatory pre-treatment and post-treatment core needle biopsies.
• Patients must have adequate hematological, liver, cardiac and kidney function within 14 days prior to first treatment:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)
• Platelet ≥ 100 X 109/L (>100, 000 per mm^3)
• Hemoglobin ≥ 8.0 g/dL
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). (Unless Gilbert's Syndrome, for which Bilirubin ≤ 3 x institutional upper limit of normal (ULN), without concurrent clinically significant liver disease) AST (SGOT)/ALT (SGPT) ≤ 3 x institutional upper limit of normal (ULN) unless liver metastases are present, in which case it must be ≤ 5x ULN.
• Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN).
• For patients of childbearing potential, agreement to use two effective forms of contraception (e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants) and to continue its use for the duration of the study and for 12 weeks after the last ZW25 dose.
• Agree to practice total abstinence when this is in line with the preferred and usual lifestyle of the subject.
• A woman is considered to be of childbearing potential unless 1 of the following applies: She is considered to be permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, tubal ligation, and bilateral oophorectomy.
• She is postmenopausal, defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 mIU/mL or higher) may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is ins