Dose-escalation, Safety and Pharmacokinetic Study of Briciclib in Advanced Solid Tumors

This will be a Phase I, 2-stage, open-label, dose-escalating, multicenter study of the
2-hour, once-a-week intravenous (IV) administration of briciclib in 3-week cycles, in up to
54 adult patients with advanced cancer and solid tumors. The study will be conducted in 2
stages: a dose-escalation stage to determine the Maximum Tolerated Dose (MTD) and a
Recommended Phase 2 Dose (RPTD) confirmation stage. Patients with stable disease (SD) or
response may remain treated on study until progression.

Inclusion Criteria:

1. Histologically confirmed solid tumor (leukemia and lymphoma are excluded)

2. Malignancy that is incurable and for which standard (FDA approved or established
standard clinical practice) curative, or palliative measures do not exist or are no
longer effective

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

4. Minimum expected life expectancy > 6 months

5. One or more measurable lesion(s) ("target lesion[s]") that can be accurately measured
in at least 1 dimension

6. Willing to adhere to the prohibitions and restrictions specified in the protocol

7. The patient must sign an informed consent form (ICF)

Exclusion Criteria:

1. Recent major surgery (within the past 14 days)

2. Chemotherapy or dose of other potentially myelosuppressive treatment within 3 weeks
prior to Screening (6 weeks for nitrosoureas or mitomycin C)

3. No more than a total cumulative dose of 450 mg/m^2 of prior doxorubicin chemotherapy

4. Definitive radiotherapy (> 10 fractions and maximal area of hematopoietic active Bone
Marrow treated greater than 25%) within 4 weeks prior to Screening

5. Palliative radiotherapy (≤ 10 fractions) within 2 weeks prior to Screening

6. Known brain metastases, except brain metastases that have been previously removed or
irradiated and currently have no clinical impact

7. Residual adverse events due to previously administered agents (except alopecia, stable
residual neuropathy, and residual hand, foot syndrome) that have not recovered to
Grade 1 or below in severity level (based on NCI CTCAE) before Screening

8. Ascites requiring active medical management, including paracentesis

9. Pleural effusion requiring active medical management

10. Peripheral bilateral edema requiring active medical management

11. Hyponatremia (serum sodium value less than 130 mEq/L)

12. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to briciclib

13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, bleeding, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements

14. History of myocardial infarction

15. Any other concurrent investigational agent or chemotherapy, radiotherapy,
hormonotherapy, or immunotherapy. Exceptions are long-term hormonals for prostate (eg,
goserelin) and octreotide for neuroendocrine malignancies

16. Patients who are positive for human immunodeficiency virus type 1 (HIV-1) and are
receiving combination anti-retroviral therapy

17. Hemoglobin (Hgb) < 9 g/dL

18. White Blood Cell count (WBC) < 4,000/µL

19. Absolute Neutrophil Count (ANC) < 1,500/µL

20. Platelet (PLT) count ≤ 100,000/µL

21. Total bilirubin greater than 1.5 x the institutional upper limit of normal (ULN)

22. Aspartate transaminase (AST) or alanine transaminase (ALT) ≥ 2.5 x institutional ULN.
If liver function abnormalities are due to metastatic disease, patients are eligible
provided the ALT and AST are < 5 x ULN

23. Serum creatinine > 2 x ULN