A Phase 1 Study Evaluating CB-5083 in Patients With Advanced Solid Tumors

The objectives of the Dose Escalation Phase are to determine the safety, tolerability, PK
and pharmacodynamic profiles as well as the MTD and RP2D of orally administered CB-5083. The
objectives of the dose expansion phase are to confirm the safety and tolerability of the
RP2D, to further assess the PK and pharmacodynamic profiles and to evaluate the preliminary
anti-tumor activity of CB-5083 in patients with tumors for which there is biologic
plausibility of unique sensitivity to CB-5083 mechanism of action (MOA) based on
pre-clinical data.

Inclusion Criteria:

For both Escalation and Expansion arms:

1. Males and females ≥18 years of age;

2. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1

3. Acceptable bone marrow and organ function at screening

4. Left ventricular ejection fraction informed (LVEF) ≥ 55%;

5. Ability to swallow and retain oral medications;

6. Negative serum beta-human Chorionic Gonadotropin (β-hCG) test in women of
childbearing potential (WOCBP); and

7. Willing and able to provide written informed consent and comply with the requirements
of the study.

8. Dose Escalation arm, only - Histologically confirmed advanced solid tumor for which
standard therapy does not exist or is no longer effective

9. Dose Expansion arm, pNET Cohort only - Histologically confirmed low-grade or
intermediate-grade, unresectable or metastatic pNET tumor with radiological
documentation of disease progression < 12 months prior to enrollment for which
standard therapy does not exist or is no longer effective. Functional and
non-functional tumors can be included;

10. Dose Expansion arm, K-RAS Cohort only - Histologically confirmed malignancy with a
K-RAS mutation that is metastatic or unresectable and for which standard therapy does
not exist or is no longer effective.

Exclusion Criteria:

Both arms

1. Any prior treatment (with the exception of somatostatin analogues, which are allowed
before and during the study in pNET patients at the investigator discretion in pNET
patients) such as chemotherapy, immunomodulatory drug therapy, anti-neoplastic
hormonal therapy (unless dose has been stable for 3 months prior to Baseline and will
remain stable during the study), immunosuppressive therapy, or corticosteroids
(unless administered to prevent contrast material reactions during radiographic
procedures) received within the past 28 days or 5 half-lives, whichever is shorter.

2. Presence of an acute or chronic toxicity resulting from prior chemotherapy, with the
exception of alopecia, that has not resolved to ≤ grade 1;

3. Received radiotherapy within the last 21 days (limited palliative radiation is
allowed if ≥ 14 days prior);

4. Patient with primary brain tumors or known central nervous system (CNS) metastases;

5. Major surgery < 28 days from the start of treatment (major surgery is defined as a
procedure requiring general anesthesia);

6. Minor surgery <14 days from the start of treatment (insertion of a vascular access
device is not considered major or minor surgery);

7. Active infection requiring systemic therapy;

8. Known to be human immunodeficiency virus (HIV) positive or have an acquired
immunodeficiency syndrome-related illness;

9. Uncontrolled congestive heart failure, angina, myocardial infarction, cerebrovascular
accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack,
or pulmonary embolism within 3 months prior to initiation of study drug;

10. History of or ongoing cardiac dysrhythmias requiring treatment, atrial fibrillation
of any grade, or persistent prolongation of the QTc;

11. History of esophageal bleeding due to varices;

12. Gastrointestinal disease that may interfere with the absorption of
orally-administered drugs;

13. History of inflammatory bowel disease or other illness resulting in chronic diarrhea;

14. Known achlorhydria or history of gastrointestinal surgery that could reduce the
acidity of the stomach;

15. Acute pancreatitis or cholecystitis within 6 months prior to Baseline;

16. Cirrhosis with severe liver dysfunction;

17. Previous malignancy, except for basal-cell or squamous cell carcinoma of the skin or
carcinoma-in-situ of the uterine cervix. Patients with other malignancies are
eligible if they have remained disease free for at least 2 years prior to study
entry;

18. Any severe, acute, or chronic medical or psychiatric condition, or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, may interfere with the informed consent process and/or with
compliance with the requirements of the study, or may interfere with the
interpretation of the study results and, in the Investigator's opinion, would make
the patient inappropriate for entry into this study;

19. Use of any investigational agents within 28 days or 5 half-lives (whichever is
shorter) prior to Baseline;

20. Concomitant treatment with pharmaceutical or herbal agents, which are potent
inhibitors or inducers of cytochrome P450 (CYP) enzymes 2C9, 2C19, and 3A4 or are
primarily metabolized by CYP 2C8 and 2C9. In addition, concomitant treatment with
agents known to be substrates of the breast cancer resistance protein (BCRP) efflux
pump is also excluded;

21. Concomitant use of drugs with a risk of causing prolonged QTc and/or Torsades de
Pointes or a history of risk factors for Torsades de Pointes;

22. Concomitant use of any medication that alters stomach pH;

23. Pregnant or lactating female; and

24. Women of childbearing potential, or men who partner with a woman of childbearing
potential, unless they agree to use dual barrier contraceptive methods which, in the
Investigator's opinion, are effective and adequate for that patient's circumstances
while on study drug and for 3 months afterward.