A Phase 1 Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX7486 as a Single Agent and in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced Solid Tumors

Inclusion Criteria:

1. Male or female ≥18 years old

2. Patients with solid tumors who:

1. Part 1: have tumor progression following standard therapy, have
treatment-refractory disease, or for whom there is no effective standard of
therapy

2. Part 2a: have received ≤2 prior chemotherapy regimens for the treatment of their
primary malignancy and for whom gemcitabine and nab-paclitaxel would be
considered a reasonable chemotherapy option

3. Part 2b: have previously untreated locally advanced, non-resectable or
metastatic pancreatic adenocarcinoma, are not candidates for FOLFIRINOX
treatment(i.e., leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin.)
Patients who received prior neoadjuvant or adjuvant therapy with recurrent
disease ≥6 months following completion of the regimen are also eligible

3. Patients in Part 2b must have measurable disease by Response Evaluation Criteria for
Solid Tumors (i.e., RECIST) criteria v1.1

4. Women of child-bearing potential must have a negative pregnancy test within 7 days of
initiation of dosing and must agree to use an acceptable method of birth control from
the time of the negative pregnancy test up to 3 months after the last dose of study
drug. Women of non-childbearing potential may be included if they are either
surgically sterile or have been postmenopausal for ≥1 year. Fertile men must also
agree to use an acceptable method of birth control while on study drug and up to 3
months after the last dose of study drug.

5. All associated toxicity from previous or concurrent cancer therapy must be resolved
(to ≤ Grade 1 or Baseline) prior to study treatment administration.

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

7. Willing and able to provide written informed consent prior to any study related
procedures and to comply with all study requirements

8. Karnofsky performance score ≥ 70%

9. Life expectancy ≥3 months.

10. Adequate hematologic, hepatic, and renal function.

Exclusion Criteria:

1. Other than the primary malignancy, active cancer (either concurrent or within the
last 3 years) that requires non-surgical therapy (e.g. chemotherapy or radiation
therapy), with the exception of surgically treated basal or squamous cell carcinoma
of the skin, melanoma in-situ, or carcinoma in-situ of the cervix.

2. Chemotherapy within 28 days prior to Screening

3. Biological therapy within 5 half-lives of Screening

4. Radiation therapy within 14 days prior to Screening

5. Investigational drug use within 28 days or 5 half-lives, whichever is longer, prior
to Screening

6. Part 1 only: active or a history of glucose intolerance or diabetes mellitus

7. Part 2a and 2b only: known hypersensitivity to gemcitabine or nab-paclitaxel

8. Part 2a and 2b: uncontrolled diabetes. Patients with glucose intolerance or diabetes
whose blood glucose levels are consistently well-controlled with the use of oral
hypoglycemic agents and/or insulin are permitted.

9. Part 2b only: received radiotherapy, surgery, chemotherapy or investigational therapy
for the treatment of metastatic pancreatic adenocarcinoma. Prior treatment with
5-Fluorouracil or gemcitabine administered as a radiation sensitizer in the adjuvant
setting is allowed, provided at least 6 months have elapsed since last dose and no
lingering toxicities.

Patients having received cytotoxic doses of gemcitabine or any other chemotherapy in
the adjuvant setting are not eligible for this study

10. Hemoglobin A1c >8%

11. ≥ Grade 2 sensory neuropathy at baseline

12. Uncontrolled intercurrent illness (i.e., active infection) or concurrent condition
that, in the opinion of the Investigator, would interfere with the study endpoints or
the patient's ability to participate

13. Refractory nausea and vomiting, malabsorption, small bowel resection that, in the
opinion of the Investigator, would preclude adequate absorption

14. Mean corrected QT interval (QTcF) ≥450 msec (for males) or ≥470 msec (for females) at
Screening

15. 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