ABT-348 as Monotherapy or Combination With Carboplatin or Docetaxel to Treat Advanced Solid Tumors

The primary purpose of this study is to determine the safety, pharmacokinetics and maximum
tolerated dose of ABT-348 as monotherapy and when given in combination with carboplatin or
docetaxel. The secondary purpose of this study is to evaluate safety at the recommended
Phase 2 dose and evaluate preliminary efficacy data regarding objective response rate time
to progression, duration of overall response, and ECOG performance status of ABT-348 as
monotherapy and when given in combination with carboplatin or docetaxel.

Inclusion Criteria:

1. Histological confirmation of locally advanced or metastatic solid tumor.

- That is either refractory after standard of care therapy for the disease for
which standard of care therapy is not reliably effective or does not exists, or

- For which carboplatin has been determined to be an appropriate therapy, per the
investigator, or

- For which docetaxel has been determined to be an appropriate therapy, per the
investigator.

2. Eastern Cooperative Oncology Group Status of 0-2

3. Serum creatinine value of ≤ 1.5 times the upper limit of normal (ULN) and either an
estimated creatinine clearance value as determined by the Cockcroft-Gault formula or
based on a 24 hour urine collection creatinine clearance value of ≥ 50 mL/min

4. Adequate liver function as demonstrated by serum bilirubin < 2 x ULN and AST and ALT
≤ 2.5 x ULN

5. Adequate bone marrow as demonstrated by absolute neutrophil count (ANC) ≥ 1,500/mm2
(1.5 x 109/L); Platelets ≥ 100,000/mm2 (100 x 109/L); Hemoglobin ≥ 9.0 g/dL (1.4
mmol/L)

6. QTc interval < 500 msec

7. Left Ventricular Ejection Fraction > 50%

8. Women of child-bearing potential and men must agree to use adequate contraception
(one of the following listed below) prior to the study entry, for the duration of
study participation and up to 3 months following completion of therapy.

9. Capable of understanding and complying with parameters as outlined in the protocol
and able to sign informed consent, approved by an Institutional Review Board (IRB)
prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

1. Subject has known active CNS involvement. The subject has untreated brain or
meningeal metastases.

2. Subject has received anti-cancer therapy within a period of 21 days or 5 half lives
(whichever is shorter) prior to Study Day 1

3. Subject has unresolved toxicities from prior anti-cancer therapy, grade 2 or higher
clinically significant toxicity (excluding alopecia)

4. Subject has had major surgery within 28 days prior to Study Day 1

5. Subject currently exhibits symptomatic or persistent, uncontrolled hypertension
defined as diastolic blood pressure > 90 mmHg or systolic blood pressure > 140 mmHg

6. Subject has proteinuria grade > 1

7. Subject is receiving therapeutic anticoagulation therapy. Low dose anti coagulation
(e.g., low dose heparin or warfarin) for catheter prophylaxis will be permitted.

8. Clinically significant uncontrolled condition(s)

9. Psychiatric illness/social situation that would limit compliance with study
requirements

10. Subject has a known infection with HIV, Hepatitis B or Hepatitis C

11. Subject with poorly controlled diabetes mellitus

12. Subject enrolled in Arm A, B, C and D is unable to swallow or absorb oral tablets
normally

13. Any medical condition which in the opinion of the study investigator places the
subject at an unacceptably high risk for toxicities

14. Female subjects who are lactating or pregnant

15. Subject enrolled in Arm E has hypersensitivity to drugs formulated with
polyethoxylated castor oli (Cremophor)