Clinical Trials

Inclusion Criteria:

1. Subjects must be aged ≥ 18 years of age inclusive, at the time of signing the informed
consent.

2. Histologically confirmed recurrent or persistent USC. Subjects with carcinosarcomas
are not eligible.

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.

Exclusion Criteria:

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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/27/22. Questions regarding updates should be directed to the study team contact.