Ph 1 Study of VS-4718, a FAK Inhibitor, in Combination With Nab-paclitaxel and Gemcitabine in Advanced Cancer Subjects

The study is comprised of 2 sequential parts: Part A (Dose Escalation of VS-4718) in
subjects with advanced cancer and Part B (Expansion) in subjects with untreated advanced
pancreatic cancer.

Up to 60 evaluable subjects (i.e., subjects who complete at least 1 cycle (28 days) of
therapy) will be enrolled, assuming that:

1. Part A: The maximum sample size will be 6 subjects up to 4 dose levels (exclusive of
replacement subjects). However, additional subjects may be added if exploration of
intermediate dose level(s) of VS 4718 is warranted. The starting dose of VS-4718 will
be 200mg BID.

2. Part B: Up to 36 additional subjects may be enrolled at the RP2D. These subjects will
be randomized at a 1:1 ratio to 1 of 2 treatment cohorts:

- Cohort 1: IV treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes
on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8,
and 15) and oral VS 4718 BID continuously starting on Day 1 of Cycle 1

- Cohort 2: IV treatment for the first 2 cycles, followed by IV treatment and oral
VS-4718 BID continuously starting on Day 1 of Cycle 3

Inclusion Criteria:

- Age ≥ 18 years

- Histologically or cytologically confirmed diagnosis of an advanced nonhematological
malignancy (Part A) or advanced pancreatic adenocarcinoma (Part B) that is not
surgically resectable

- Eligible for treatment with nab-paclitaxel and gemcitabine on Days 1, 8, and 15 in
28-day cycles as standard therapy

- Evaluable or measurable disease, as assessed by RECIST v1.1

- ECOG performance status of ≤ 1

- Adequate renal function (creatinine ≤ 1.5×ULN [upper limit of normal]) or glomerular
filtration rate of ≥ 60 mL/min

- Adequate hepatic function (total bilirubin ≤ 1.5×ULN for the institution; aspartate
transaminase and alanine transaminase ≤ 2.5×ULN, or ≤ 5×ULN if due to liver
involvement by tumor; albumin ≥ 3 g/dL)

- Adequate bone marrow function (hemoglobin ≥ 9.0 g/dL; unsupported platelets ≥ 100×109
cells/L; absolute neutrophil count [ANC] ≥ 1.5×109 cells/L without the use of
hematopoietic growth factors)

- Corrected QT interval (QTc) < 470 ms

- Willing and able to participate in the trial and comply with all trial requirements

Exclusion Criteria:

- Gastrointestinal (GI) condition that could interfere with the swallowing or
absorption of study medication

- Uncontrolled or severe concurrent medical condition (including uncontrolled brain
metastases).

- History of upper gastrointestinal bleeding, ulceration, or perforation within 6
months prior to the first dose of protocol therapy

- Known history of stroke or cerebrovascular accident within 6 months prior to the
first dose of protocol therapy.

- Part B only: Prior therapy (including investigational agents) for pancreatic cancer

- Chemotherapy or radiotherapy within 14 days prior to first dose of protocol therapy

- Active treatment for a secondary malignancy