This is a Phase I/Ib, open-label, multicenter, dose-escalation trial of paclitaxel in combination with defactinib (VS-6063), a focal adhesion kinase inhibitor, in patients with advanced ovarian cancer. This clinical study is comprised of 2 parts: Phase I (Dose Escalation) and Phase Ib (Expansion). The purpose of this study is to assess assess the safety (including the recommended phase 2 dose), the pharmacokinetics, and the anti-cancer activity of defactinib (VS-6063) when administered in combination with paclitaxel. Pharmacodynamic effects will also be examined in tumor biopsies.

Inclusion Criteria:

1. Able to provide signed and dated informed consent prior to initiation of any study procedures.
2. Female subjects aged ≥ 18 years.
3. Advanced or refractory ovarian cancer, confirmed histologically.
4. Subjects may have received up to 4 prior lines of chemotherapy for their metastatic disease.
5. All persistent clinically significant toxicities from prior chemotherapy must be ≤ Grade 1.
6. ECOG performance status of 0 or 1 (refer to Appendix A), measured within 72 hours before the start of treatment.
7. Predicted life expectancy of ≥ 3 months.
8. Adequate renal function [creatinine ≤ 1.5x ULN (upper limit of normal)] or GFR of ≥ 50mL/min.
9. Adequate hepatic function (total bilirubin ≤ 1.5x ULN for the institution; AST [aspartate transaminase] and ALT [alanine transaminase] ≤ 3x ULN, or ≤ 5x ULN if due to liver involvement by tumor).
10. Adequate bone marrow function (hemoglobin ≥ 9.0 g/dL; platelets≥ 100 x109cells/L; absolute neutrophil count ≥ 1.5x109 cells/L).
11. Corrected QT interval (QTc) < 470 ms (as calculated by the Fridericia correction formula).
12. Negative pregnancy test for females of child-bearing potential; must be surgically sterile, postmenopausal, or willing and able to be compliant with a contraceptive regimen (double barrier birth control) during and for 3 months after the treatment period.
13. Willing and able to participate in the trial and comply with all trial requirements.

Exclusion Criteria:

1. Gastrointestinal (GI) condition which could interfere with the swallowing or absorption of study medication.
2. Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases). Stable brain metastases either treated or being treated with a stable dose of steroids/anticonvulsants, with no dose change within 28 days prior to the first dose of study drug, will be allowed.
3. History of upper gastrointestinal bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug.
4. Known history of Gilbert's Syndrome.
5. Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug.
6. Subjects with known infection with human immunodeficiency virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) (testing not required).
7. Subjects with Hepatitis A, B or C (testing not required).
8. Subjects being actively treated for a secondary malignancy.
9. Cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy, biologic or immunotherapy, etc.) within 28 days of the first dose of study drug or 5 half-lives, whichever is shorter.
10. Major surgery within 28 days prior to the first dose of study drug.
11. Use of an investigational drug within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug. A minimum of 10 days between termination of the investigational drug and administration of the study treatment is required. In addition, any drug-related toxicity except alopecia should have recovered to grade 1 or less.
12. Pregnant or breastfeeding.
13. Any evidence of serious active infections.
14. Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis.
15. Uncontrolled intercurrent illness including symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.