A Study of Adavosertib as Treatment for Uterine Serous Carcinoma

Exclusion Criteria

• •3. Evidence of measurable disease as per RECIST v1.1.
• •4. At least 1 prior platinum-based chemotherapy regimen for the management of USC. Prior receipt of immune checkpoint inhibitors, vascular endothelial growth factor (VEGF) inhibitors and human epidermal growth factor receptor 2 (HER2) targeted therapy is allowed. There is no restriction on the number of prior lines of systemic therapy.
• •5. Eastern Cooperative Oncology Group performance (ECOG) status 0-1.
• •6. Life expectancy ≥ 12 weeks.
• •7. Subjects must have normal organ and marrow function at baseline, within 7 days prior to study drug administration.
• •8. Consent to submit and provide a mandatory Formalin-fixed paraffin-embedded tumor sample for central testing.
• •9. Female subjects who are not of childbearing potential and women of childbearing potential who agree to use adequate contraceptive measures.
• •1. Any underlying medical condition and uncontrolled intercurrent illness that would impair the ability of the subject to receive study treatment, as judged by the investigator.
• •2. With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment.
• •3. Unable to swallow oral medications.
• •4. Spinal cord compression or metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
• •5. Subjects with current signs or symptoms of bowel obstruction, including sub-occlusive disease, related to underlying disease.
• •6. Any of the following cardiac diseases currently or within the last 6 months:
• •* Unstable angina pectoris
• •* Acute myocardial infarction
• •* Congestive heart failure
• •* Conduction abnormality not controlled with pacemaker or medication
• •* Significant ventricular or supraventricular arrhythmias
• •7. History of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected.
• •8. a) Resting corrected QTc interval using the Fridericia formula (QTcF) \> 480 msec, or b) congenital long QT syndrome.
• •9. Immunocompromised subjects.
• •10. Subjects with known active hepatitis (ie, hepatitis B or C).
• •11. Prior treatment with any of the following:
• •* Cell cycle checkpoint inhibitor.
• •* Anticancer treatment drug ≤ 21 days (≤ 6 weeks for nitrosoureas or mitomycin C) or use of an investigational product within 5 half-lives prior to the first dose of adavosertib. For Programmed cell death-1 receptor (PD-1) /Programmed death-ligand 1 (PD-L1) inhibitors, a minimum of 28 days since last dose is required.
• •* Prescription or non-prescription drugs known as moderate to strong inhibitors / inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment.
• •* Herbal medications 7 days prior to first dose of study treatment.
• •12. Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation within 4 weeks prior to the first dose of study intervention.
• •13. Major surgical procedures ≤ 28 days, or minor surgical procedures ≤ 7 days, prior to beginning study.
• •14. Subjects with a known hypersensitivity or contraindication to adavosertib or any of the excipients of the product.
• •15. Currently pregnant or breast-feeding.