ph 1 study of vs-4718, a fak inhibitor, in combination with nab-paclitaxel and gemcitabine in advanced cancer subjects

Conditions: Pancreatic Cancer

Summary: the purpose of this study is to evaluate increasing dose levels of vs-4718 administered in combination with gemcitabine and nab-paclitaxel in subjects with advanced cancer and to determine a recommended phase 2 dose (rp2d) for further development of this combination in subjects with untreated advanced pancreatic cancer.

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

Eligibility criteria:
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