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
Part 1 of the study is an open label, sequential PLX7486-TsOH single-agent dose escalation
in patients with solid tumors. This part of the study will include approximately 50 solid
tumor patients from 3-6 treatment sites. The starting dose will be 30 mg. Each treatment
cycle will be 21 days. Cohorts of 3 patients will be enrolled in a standard '3+3' design.
In the absence of drug-related Grade 2 toxicity, the dose escalation will occur in 100%
increments. The dose escalation will be reduced in increments of approximately 50% or less
if there is either a dose-limiting toxicity (DLT) or at least 2 patients in one cohort
experience ≥ Grade 2 toxicities that are considered possibly or probably related to PLX7486.
In part 1, the secondary objective is efficacy, as measured by overall response rate,
clinical benefit response rate, duration of response, and progression-free survival.
Exploratory endpoints will include changes in pain severity scores and analgesic consumption
and investigation of peripheral blood biomarkers and archival tumor tissue.
Part 2a of the study is also an open-label, sequential dose escalation of PLX7486-TsOH with
fixed dose levels of gemcitabine + nab-paclitaxel in patients with solid tumors.
Approximately 30 solid tumor patients will be enrolled using the standard '3+3' design.
Part 2b extension cohort is planned at the recommended phase 2 dose (RP2D) of PLX7486-TsOH
in combination with fixed dose levels of gemcitabine and nab-paclitaxel in 28-day treatment
cycles. Approximately 50 patients with previously untreated pancreatic adenocarcinoma will
be enrolled to ensure 38 patients (28 patients with metastatic disease and 10 patients with
locally advanced disease)will be evaluable for response.
In parts 2a and 2b, secondary endpoints include best overall response rate, duration of
response, clinical benefit response rate, and pharmacokinetics. Exploratory endpoints for
both parts 2a and 2b will include changes in pain severity scores and analgesic consumption,
and investigation of biomarker data in peripheral blood and archival tumor tissue.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety of PLX7486 as single agent and in combination with gemcitabine and nab-paclitaxel
Adverse events, physical examinations, vital signs, clinical laboratory tests (hematology, chemistry, and urinalysis), ECGs, ophthalmic examinations, will all be evaluated to determine dose-limiting toxicities, i.e., any adverse event that is temporally related to the study drug administration and is not due to the patient's underlying malignancy and for which there is no clear evidence for an alternative etiology.
Measured from baseline and weekly for the duration of drug administration, estimated to be ≤1 year.
Mai H Le, MD
United States: Food and Drug Administration
|Sarah Cannon Research Institute (SCRI)||Nashville, Tennessee 37203|
|Translational Genomics Research Institute (TGen)||Scottsdale, Arizona 85258|
|University of California, Los Angeles Medical Center (UCLA)||Santa Monica, California 90404|
|Medical Universtiy of South Carolina (MUSC)||Charleston, South Carolina 29425|