This is a non-randomized Phase 2 study of sacituzumab govitecan (IMMU-132) in subjects with
persistent or recurrent endometrial carcinoma.
- Patients must have radiologically confirmed (ie, CAT scan and/or MRI) persistent or
recurrent EC of epithelial origin that has progressed after prior platinum based
chemotherapy or is refractory to platinum-based chemotherapy and has at least 2+
staining for Trop-2.
- Must have availability of archival tumor tissue FFPE block for TROP-2 testing or
newly acquired biopsy (FFPE block) from a metastatic site. Bone biopsies are not
- The diagnosis must be histologically confirmed by a gynecologic pathologist.
- All patients must have measurable disease. Measurable disease is defined as lesions
which can be measured by physical examination or by means of medical imaging
techniques. Measurable disease is defined as at least one lesion that can be
accurately measured in at least one dimension (longest dimension to be recorded). Each
lesion must be ≥ 20 mm when measured by conventional techniques, including palpation
or plain x-ray, or ≥ 10 mm when measured by spiral CT and/or MRI. Ascites and pleural
effusions are not to be considered measurable disease.
- Patients must have at least one "target lesion" to be used to assess response on this
protocol as defined by RECIST v1.1. Tumors within a previously irradiated field will
be designated as "non-target" lesions unless progression is documented or a biopsy 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) are
eligible 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, Granulocytes greater than or
equal to 1500/ul.
- Patients must have adequate renal function: creatinine less than or equal to 2.0
- 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 liver
- 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 are permitted).
- Patients must have recovered from all acute toxicities to Grade 1 or less from adverse
events due to a previously administered agent.
- Note: Patients with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception
to this criterion and may qualify for the study
- Note: If patients received major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
- Patients with recurrent disease may have received multiple prior chemotherapies for
treatment of their endometrial cancer.
- Patients may have received prior immunotherapy therapy alone or in combination with
chemotherapy. A 4-week washout period is required between prior immunotherapy
treatment and first dose of sacituzumab govitecan.
- 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 contraception
during the study and until conclusion of 12-week post-treatment evaluation period.
- Patients must be at least 18 years of age.
- Have an active second malignancy. Note: Patients with a history of malignancy that has
been completely treated, with no evidence of active cancer for 3 years prior to
enrollment, or subjects with surgically-cured tumors with low risk of recurrence are
allowed 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 (other than
stable atrial fibrillation) requiring antiarrhythmia therapy.
- Patients with known history of clinically significant active COPD, or other
moderate-to-severe chronic respiratory illness present within 6 months.
- Patients with any unstable medical issue (including cardiac issues as above, active
treatment 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 with
previously treated brain metastases may participate provided they have stable CNS
disease for at least 4 weeks prior to the first dose of study drug and all neurologic
symptoms have returned to baseline, have no evidence of new or enlarging brain
metastases, and are taking ≤ 20 mg/day of prednisone or its equivalent. All patients
with carcinomatous meningitis are excluded regardless of clinical stability.
- 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 that
may interfere with SN-38 metabolism.
- Have active HBV or HCV. In subjects with a history of HBV or HCV, subjects with a
detectable viral load will be excluded.
- Known hemorrhagic diathesis or active bleeding disorder.
- Patients with Gilbert's disease.
- Presence of bulky disease (defined as any single mass >7 cm in its greatest
dimension). Patients with a mass over 7 cm, but otherwise eligible, may be considered
- Patients with active ≥ grade 2 anorexia, nausea or vomiting, diarrhea, and/or signs of
- Prior history of clinically significant bleeding, intestinal obstruction, or GI
perforation within 6 months of initiation of study treatment.
- Patients with a history of an anaphylactic reaction to irinotecan or ≥ Grade 3 GI
toxicity to prior irinotecan.
- Patients who have previously received topoisomerase I inhibitors.