A Study of Sacituzumab Govitecan (IMMU-132) in Endometrial Carcinoma

Inclusion Criteria:

• Patients must have radiologically confirmed (ie, CAT scan and/or MRI) persistent orrecurrent EC of epithelial origin that has progressed after prior platinum basedchemotherapy or is refractory to platinum-based chemotherapy.

• Must have availability of archival tumor tissue FFPE block for TROP-2 testing

• Note: The presence or absence of TROP-2 overexpression will NOT determineeligibility for study enrollment.

• The diagnosis must be histologically confirmed by a gynecologic pathologist.

• All patients must have measurable disease. Measurable disease is defined as lesionswhich can be measured by physical examination or by means of medical imagingtechniques. Measurable disease is defined as at least one lesion that can beaccurately measured in at least one dimension (longest dimension to be recorded).Each lesion must be ≥ 20 mm when measured by conventional techniques, includingpalpation or plain x-ray, or ≥ 10 mm when measured by spiral CT and/or MRI. Ascitesand pleural effusions are not to be considered measurable disease.

• Patients must have at least one "target lesion" to be used to assess response onthis protocol as defined by RECIST v1.1. Tumors within a previously irradiated fieldwill be designated as "non-target" lesions unless progression is documented or abiopsy is obtained to confirm persistence following completion of radiation therapy.

• After undergoing surgery, patients may be optimally or sub optimally debulked.

• Patients with measurable recurrent disease of any previous substage (I-IV) areeligible to enrollment.

• Patients must have adequate bone marrow function: WBC greater than or equal to 3,000/ul, Platelets greater than or equal to 75,000/ul, Neutrophils greater than orequal to 1500/ul.

• Patients must have adequate renal function: creatinine less than or equal to 2.0mg/dL.

• Patients must have adequate hepatic function: Bilirubin ≤ 1.5 X laboratory normal.SGOT/SGPT ≤ 3 X laboratory normal or ≤ 5 X laboratory normal if known livermetastases.

• Patients must have an ECOG performance status of 0 or 1.

• Patients must have signed an approved informed consent.

• Patients must be at least 2 weeks beyond prior treatment (chemotherapy,investigational drugs including small molecular inhibitors, endocrine therapy,immunotherapy and/or radiation therapy) or major surgery.

• Patients must be at least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids ≤ 20 mg prednisone or equivalent daily arepermitted).

• Patients must have recovered from all acute toxicities to Grade 1 or less fromadverse events due to a previously administered agent.

• Note: Patients with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exceptionto this criterion and may qualify for the study

• Note: If patients received major surgery, they must have recovered adequatelyfrom the toxicity and/or complications from the intervention prior to startingtherapy

• Patients with recurrent disease may have received multiple prior chemotherapies fortreatment of their endometrial cancer.

• Patients may have received prior immunotherapy therapy alone or in combination withchemotherapy.

• Patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the study entry and be practicing an effective form of contraceptionduring the study and until conclusion of 12-week post-treatment evaluation period.

• Patients must be at least 18 years of age.

Exclusion Criteria:

• Have an active second malignancy. Note: Patients with a history of malignancy thathas been completely treated, with no evidence of active cancer for 3 years prior toenrollment, or subjects with surgically-cured tumors with low risk of recurrence areallowed to enroll.

• Patients with a significant history of cardiac disease within 6 months, i.e.,uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure (NYHA classification III-IV) or clinically significant cardiac arrhythmia (otherthan stable atrial fibrillation) requiring antiarrhythmia therapy.

• Patients with known history of clinically significant active COPD, or othermoderate-to-severe chronic respiratory illness present within 6 months.

• Patients with any unstable medical issue (including cardiac issues as above, activetreatment for symptomatic pulmonary embolism, CVA, renal or hepatic insufficiency,and active infection/sepsis requiring IV antibiotics).

• Have known active CNS metastases and/or carcinomatous meningitis. Patients withpreviously treated brain metastases may participate provided they have stable CNSdisease for at least 4 weeks prior to the first dose of study drug and allneurologic symptoms have returned to baseline, have no evidence of new or enlargingbrain metastases, and are taking ≤ 20 mg/day of prednisone or its equivalent. Allpatients with carcinomatous meningitis are excluded regardless of clinicalstability.

• Patients who have an uncontrolled seizure disorder, or active neurological disease.

• Have a known history of HIV-1/2 with uncontrolled viral load and on medications thatmay interfere with SN-38 metabolism.

• Have active HBV or HCV. In subjects with a history of HBV or HCV, subjects with adetectable viral load will be excluded.

• Known hemorrhagic diathesis or active bleeding disorder.

• Patients with Gilbert's disease.

• Patients with active ≥ grade 2 anorexia, nausea or vomiting, diarrhea, and/or signsof intestinal obstruction.

• Prior history of clinically significant bleeding, intestinal obstruction, or GIperforation within 6 months of initiation of study treatment.

• Patients with a history of an anaphylactic reaction to irinotecan or ≥ Grade 3 GItoxicity to prior irinotecan.

• Patients who have previously received topoisomerase I inhibitors.