Open-label Phase 1b Study of ARQ 092 in Combination With Anastrozole

This is an open-label Phase 1b, dose escalation study of oral ARQ 092 administered in
combination with carboplatin plus paclitaxel (Carboplatin Plus Paclitaxel Arm) or in
combination with paclitaxel alone (Paclitaxel Arm), in subjects with advanced, inoperable
metastatic and/or recurrent solid tumors, or in combination with anastrozole (Anastrozole
Arm) in subjects with ovarian or endometrial cancer.

Enrollment in the Carboplatin plus Paclitaxel Arm and Paclitaxel Alone Arm is now closed.
Enrollment in the Expansion Cohort for the Anastrozole Arm continues for patients with
Endometrial cancer.

Inclusion Criteria:

1. Signed written informed consent form

2. 18 years of age or older

3. Histologically or cytologically confirmed locally advanced, inoperable, or metastatic
tumors:

- Subjects with endometrial cancer with:

- Documented/locally determined AKT1, PIK3CA, or PIK3R1 mutations with or
without PTEN deficiency

- ER+ status

4. Female subjects of child-bearing potential must have a negative serum or urine
pregnancy test within 72 hours prior to administration of the first dose of study
drug. "Women of childbearing potential" is defined as sexually mature women who have
not undergone hysterectomy and/or bilateral oophorectomy, or who have not been
naturally postmenopausal for at least 12 consecutive months prior to administration of
the first dose of the study drug.

5. Measurable or evaluable disease

6. Subjects must agree to provide requested amount of archival and/or fresh tissue biopsy
samples at baseline for mutational analysis by the Sponsor's central laboratory.

7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

8. Life expectancy ≥ 12 weeks

9. Failure to respond to or refractory to approved/standard therapy; or for whom standard
therapy does not exist, or is not tolerable; or for whom approved/standard therapy is
not considered to be sufficient or appropriate by the Investigator.

10. Adequate organ function as indicated by the following laboratory values. All
laboratory tests must be obtained within 7 days prior to the first dose of study
treatment:

- Hematological

- Absolute neutrophil count (ANC) ≥ 1.0 x 109/L

- Platelet count (Plt) ≥ 100 x 109/L

- Hemoglobin (Hb) ≥ 8 g/dL

- Renal

- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or

- Calculated creatinine clearance ≥ 60 mL/min /1.73 m2 for subjects with serum
creatinine levels > 1.5 x institutional ULN

- Hepatic

- Total bilirubin ≤ 1.5 x ULN or

- Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN

- AST and ALT ≤ 3 x ULN or ≤ 5 x ULN for subjects with known liver metastases

- Metabolic - Glycated hemoglobin (HbA1c) ≤ 8%

11. If a subject is currently receiving bisphosphonates or denosumab, the subject must
have received the bisphosphonates or denosumab for at least four weeks before starting
study treatment. Initiation of bisphosphonates or denosumab during the study may be
allowed provided the subject completes the first cycle of treatment without any DLT
and the Investigator rules out tumor progression.

12. Male or female subjects of child-bearing potential must agree to use double-barrier
contraceptive measures, oral contraception, or avoidance of intercourse during and
after the study (3 months after the last dose of ARQ 092 or anastrozole, whichever is
longer)

Exclusion Criteria:

1. Anti-cancer therapy, such as chemotherapy, immunotherapy, targeted and
hormonal/endocrine therapy, or investigational agents within five half-lives or two
weeks (whichever is shorter) for oral drugs, five half-lives or four weeks (whichever
is shorter) for intravenous drugs, and six weeks for nitrosoureas, mitomycin C, or
bevacizumab prior to administration of the first dose of study drug

- To be eligible for study treatment, toxicity from prior treatment must recover to
Grade ≤ 1, except for alopecia

- Concurrent systemic high-dose corticosteroids when used intermittently in an
antiemetic regimen for central nervous system (CNS) metastases management or as a
part of the premedication regimen are allowed

- Prior hormonal therapy (including, but not limited to, tamoxifen, megestrol
acetate, fulvestrant, and GnRH analogs) for the treatment of recurrent/advanced
endometrial cancer are not allowed

2. Radiation therapy within four weeks prior to administration of the first dose of study
drug

• To be eligible for study treatment, radiation therapy-related toxicity must recover
to Grade ≤ 1 prior to administration of the first dose of study drug. Concurrent
palliative radiotherapy for local pain-control may be allowed, provided the subject
does not meet criteria of progressive disease and treated lesions will not be included
in the target/non-target lesion assessment.

3. Major surgical procedure within four weeks prior to administration of the first dose
of study drug

• To be eligible for study treatment, all surgical wounds must be fully healed and any
surgery-related adverse events (AE) must recover to Grade ≤ 1

4. Previous treatment with AKT inhibitors (e.g., MK-2206, GSK2141795, AZD5363)

5. Contraindications to treatment with anastrozole defined by the Investigator based on
institutional Standard of Care (SOC), scientific evidence, expert medical judgment, or
published literature

6. History of allergic reaction attributed to compound(s) of similar chemical or biologic
composition as ARQ 092 or anastrozole

7. Unable or unwilling to swallow ARQ 092 or anastrozole

8. Known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis

• To be eligible for the study treatment, subjects must have stable disease ≥ 3
months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT)
scan, and have CNS metastases well controlled by low-dose steroids, anti-epileptics,
or other symptom-relieving medications

9. History of myocardial infarction (MI) or congestive heart failure defined as Class II
to IV per the New York Heart Association (NYHA) classification within 6 months of the
first dose of ARQ 092 (MI that occurred > 6 months prior to the first dose of ARQ 092
will be permitted)

10. History of Type 1 or 2 diabetes mellitus requiring regular medication (other than oral
hypoglycemic agents including metformin) or fasting glucose ≥ 160 mg/dL

11. Significant gastrointestinal disorder(s), that could in the opinion of the
Investigator, interfere with the absorption, metabolism, or excretion of ARQ 092
(e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)

12. Previous malignancy within 2 years of the first dose of study drugs, except tumors
totally resected and/or not requiring therapy

13. Concurrent uncontrolled illness not related to cancer, including but not limited to:

• Ongoing or active infection, including human immunodeficiency virus (HIV), hepatitis
B (HBV) (hepatitis B surface antigen [HBsAg] positive; subjects with documented
laboratory evidence of HBV clearance may be enrolled) or hepatitis C (HCV) (positive
HCV antibody), or bleeding

14. Psychiatric illness, substance abuse, and/or social situation that would limit
compliance with study requirements

15. Blood transfusion within 5 days of the blood draw being used to confirm eligibility

16. Pregnant or breastfeeding