Safety Study of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors

Inclusion Criteria:

- Patients with:

- Part 1 (enrollment closed): an advanced, incurable solid tumor

- Part 2 (enrollment closed): an advanced, incurable solid tumor for whom a taxane
would be considered a reasonable chemotherapy option

- Part 3 (enrollment closed): advanced, metastatic or non-resectable epithelial
ovarian cancer, primary peritoneal cancer or fallopian tube cancer with

- platinum-resistant cancer, defined as disease that responded to a
platinum-containing chemotherapy regimen, but demonstrated recurrence within
six months following the completion of that platinum-containing regimen, OR

- platinum-refractory cancer, defined as disease failed to achieve at least a
partial response to a platinum-containing regimen (i.e., stable disease or
actual disease progression), AND

- have not been treated with a taxane within six months of C1D1, AND

- have not been treated with weekly paclitaxel after first-line treatment in
which weekly paclitaxel plus a platinum is permitted

- Part 3: Patients must have target (≥2 cm diameter) or non-target lesion cancer that is
accessible for core biopsies before starting on study and after one cycle of
treatment.

- Patients with stable brain metastases are eligible for this trial. However, patients
must not have required steroid treatment for their brain metastases within 30 days of
Screening.

- Bone-directed therapy (e.g., bisphosphonates or denosumab) is permitted.

- Washout from any prior investigational therapy of at least five times the T1/2 prior
to C1D1

- Washout from any prior biologic or targeted therapy at least 4 weeks or five times the
T1/2 (whichever is shorter) prior to C1D1

- Washout from prior chemotherapy of at least 2 weeks or 1 elimination half-life,
whichever is longer, prior to C1D1

- Washout from prior hormonal therapy of at least 2 weeks prior to C1D1

- Washout of at least 2 weeks from the most recent radiation treatment prior to C1D1

- Resolution of all prior treatment-related toxicities to Grade 1 or less, except for
Grade 2 fatigue or alopecia prior to C1D1

- Age eighteen years or older

- ECOG performance status 0-2, inclusive

- Anticipated life expectancy of at least 12 weeks

- Adequate bone marrow reserve: ANC ≥1500/mm3, platelets ≥100,000/mm3

- Adequate renal function: serum creatinine <1.5 x ULN or calculated CrCl >60 mL/min
using Cockcroft-Gault formula

- Adequate hepatic function: AST and ALT <2.5 x ULN, Total and Direct Bilirubin <1.5 x
ULN. However, in the presence of liver metastases, AST and ALT must be <5 x ULN

- Cardiac ejection fraction ≥50%, and QTcF<450 ms (males) or <470 ms (females) on ECG at
Baseline.

- Able to swallow capsules and maintain adequate hydration

- Ability to give written informed consent and willing to comply with the requirements
of the protocol; and for Part 3, to give written informed consent for 2 cancer biopsy
procedures

- Women of child-bearing potential must agree to use an effective method of birth
control during treatment and for three months after receiving their last dose of study
drug. Fertile men must also agree to use an acceptable method of birth control while
on study drug and for at least 3 months after last dose.

Exclusion Criteria:

- Presence of an active secondary malignancy.

- Patients with a non-melanomatous, in situ malignancy or disease that is
completely resectable with surgery may be considered after discussion with the
Medical Monitor

- Patients with a completely treated prior malignancy with no evidence of disease
for ≥3 years are eligible

- Refractory nausea and vomiting, malabsorption, external biliary shunt or significant
small bowel resection that would preclude adequate absorption of PLX3397

- Ongoing treatment with any other investigational therapy

- Prior anaphylactic or severe hypersensitivity reaction to paclitaxel or
Cremophor-containing agent.

- Persistent grade 2 fatigue at Baseline.

- Severe, concurrent illness including congestive heart failure, significant cardiac
disease and uncontrolled hypertension, that would likely prevent the patient from
being able to comply with the study protocol

- Active untreated infection

- Known chronic active Hepatitis B or C, or HIV infection

- The presence of a medical or psychiatric condition that, in the opinion of the
Principal Investigator, makes the patient inappropriate for inclusion in this study.