A Study of Adavosertib as Treatment for Uterine Serous Carcinoma

Inclusion Criteria

• Subjects must be aged ≥ 18 years of age inclusive, at the time of signing the informed consent.
• Histologically confirmed recurrent or persistent USC. Subjects with carcinosarcomas are not eligible.
• Evidence of measurable disease as per RECIST v1.1.
• 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.
• Eastern Cooperative Oncology Group performance (ECOG) status 0-1.
• Life expectancy ≥ 12 weeks.
• Subjects must have normal organ and marrow function at baseline, within 7 days prior to study drug administration.
• Consent to submit and provide a mandatory Formalin-fixed paraffin-embedded tumor sample for central testing.
• Female subjects who are not of childbearing potential and women of childbearing potential who agree to use adequate contraceptive measures.

Exclusion Criteria

• 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.
• 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.
• Unable to swallow oral medications.
• Spinal cord compression or metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
• Subjects with current signs or symptoms of bowel obstruction, including sub-occlusive disease, related to underlying disease.
• 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
• History of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected.
• a) Resting corrected QTc interval using the Fridericia formula (QTcF) > 480 msec, or b) congenital long QT syndrome.
• Immunocompromised subjects.
• Subjects with known active hepatitis (ie, hepatitis B or C).
• 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.
• 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.
• Major surgical procedures ≤ 28 days, or minor surgical procedures ≤ 7 days, prior to beginning study.
• Subjects with a known hypersensitivity or contraindication to adavosertib or any of the excipients of the product.
• Currently pregnant or breast-feeding.