A PHASE 2 STUDY OF ACR-368 THERAPY IN SUBJECTS WITH ENDOMETRIAL CANCER

This is an open label Phase 2 study to evaluate the efficacy and safety of ACR-368 as
monotherapy or with ultra-low dose gemcitabine (ULDG) sensitization in participants with
endometrial cancer.

Inclusion Criteria: General

1. Participant must be able to give signed, written informed consent.

2. Participant must have histologically documented, high-grade endometrial cancer.

3. Treatment History Requirements:

1. Subject must have received prior platinum-based chemotherapy

2. Subject must have received prior anti-PD-(L)1 therapy

4. Participant must have histologically confirmed metastatic cancer that has progressed
during or after at least 1 prior therapeutic regimen.

5. Participant must have at least 1 measurable lesion per RECIST v1.1 criteria (by
local Investigator) in a baseline tumor imaging that has been obtained within 28
days of the treatment start. Participant must have radiographic evidence of disease
progression based on RECIST v1.1 criteria following the most recent line of
treatment.

6. Arm 1 and 2 only: Participant must be willing to provide tissue from a newly
obtained tumor biopsy from an accessible tumor lesion not previously irradiated
after written informed consent.

Newly obtained is defined as a specimen taken after written informed consent is
obtained, during the 28-day Screening period.

7. Participant must be willing to provide an archival tumor tissue block or at least 20
unstained slides, if available.

8. Participant must have stabilized or recovered (Grade 1 or baseline) from all prior
therapy related toxicities, except as follows:

1. Alopecia is accepted.

2. Endocrine events from prior immunotherapy stabilized at ≤ Grade 2 due to need
for replacement therapy are accepted (including hypothyroidism, diabetes
mellitus, or adrenal insufficiency).

3. Neuropathy events from prior cytotoxic therapies stabilized at ≤ Grade 2 are
accepted.

9. Participant must have an Eastern Cooperative Oncology Group Performance Status 0 or
1.

10. Participant must have an estimated life expectancy of longer than 3 months.

11. Participant must have adequate organ function at Screening, defined as:

1. Absolute neutrophil count > 1500 cells/µL without growth factor support within
1 week prior to obtaining the hematology values at Screening.

2. Hemoglobin ≥ 9.0 g/dL.

3. Platelets ≥ 150,000 cells/µL without transfusion within 1 week prior to
obtaining the hematology values at Screening.

4. Calculated creatinine clearance (CrCl) ≥ 50 mL/min as calculated by the
Cockcroft-Gault formula.

5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper
limit of normal (ULN); ≤ 5 × ULN if liver metastases are present.

6. Total bilirubin ≤ 1.5 × ULN not associated with Gilbert's syndrome. If
associated with Gilbert's syndrome ≤ 3 x ULN is acceptable.

7. Serum albumin ≥ 3 g/dL.

12. Participant must have adequate coagulation profile as defined below if not on
anticoagulation. If subject is receiving anticoagulation therapy, then subject must
be on a stable dose of anticoagulation for ≥ 1 month:

1. Prothrombin time within 1.5 x ULN.

2. Activated partial thromboplastin time within 1.5 x ULN.

Exclusion Criteria: General

1. Participant with known symptomatic brain metastases requiring > 10 mg/day of
prednisolone (or its equivalent). Participants with previously diagnosed brain
metastases are eligible if they have completed their treatment, have recovered from
the acute effects of radiation therapy or surgery prior to the start of ACR-368
treatment, fulfill the steroid requirement for these metastases, and are
neurologically stable based on central nervous system imaging ≥ 4 weeks after
treatment.

2. Participant has mesenchymal tumors of the uterus.

3. Participant has a history of clinically meaningful ascites, defined as history of
paracentesis or thoracentesis with therapeutic intent, within 4 weeks of Screening.
Subjects with planned therapeutic paracentesis or thoracentesis between Screening
and Cycle 1 Day 1 dosing are excluded.

4. Participant had systemic therapy or radiation therapy within 3 weeks prior to the
first dose of study drug.

5. Participants has known human immunodeficiency virus (HIV), hepatitis B, or hepatitis
C infection that is considered uncontrolled based on the criteria included in
Appendix 2.

6. Participant has a history of clinically meaningful coagulopathy, bleeding diathesis.

7. Participant has cardiovascular disease, defined as:

1. Uncontrolled hypertension defined as blood pressure > 160/90 mmHg at Screening
confirmed by repeat (medication permitted).

2. History of torsades de pointes, significant Screening electrocardiogram (ECG)
abnormalities, including ventricular rhythm disturbances, unstable cardiac
arrhythmia requiring medication, pathologic symptomatic bradycardia, left
bundle branch block, second degree atrioventricular (AV) block type II, third
degree AV block, Grade ≥ 2 bradycardia, uncorrected hypokalemia not amenable to
correction, congenital long QT syndrome, prolonged QT interval due to
medications, corrected QT based on Fridericia's formula (QTcF) > 450 msec (for
men) or > 470 msec (for women).

3. Symptomatic heart failure (per New York Heart Association guidelines;
(Caraballo, 2019), unstable angina, myocardial infarction, severe
cardiovascular disease (ejection fraction < 20%, transient ischemic attack, or
cerebrovascular accident within 6 months of Day 1).

8. Participant has a history of major surgery within 4 weeks of Screening.

9. Participant has experienced bowel obstruction related to the current cancer within
the last 6 months or signs or symptoms of intestinal obstruction, which include
nausea, vomiting, or objective radiologic finding of bowel obstruction in the last 4
weeks before the start of the treatment.

10. Participant has taken a prior cell cycle CHK1 inhibitor, including ACR-368