Evaluation of the Safety, Pharmacokinetics and Efficacy of Four Doses of YN968D1 in Subjects With Solid Tumors
Part 1 will include a sequential evaluation of 3 subjects per cohort; cohort 1 at a dose of
100 mg YN968D1, followed by a cohorts 2, 3 and 4 at doses of 250 mg, 500 mg and 750 mg
respectively. Initially, each subject will receive one dose of YN968D1 followed by a 7-Day
observation period, during which single dose PK assessments and safety monitoring will be
performed. If the initial dose is well tolerated, the subject will return on Day 8 and
receive 28-Days of continuous YN968D1 oral administration daily. Each subject will
subsequently be assessed for safety and disease progression on Day 35±2 and steady state
pharmacokinetic sampling will be obtained. Patients may continue on therapy for an
additional 28-Day cycles without dose interruption if the therapy is well tolerated.
Efficacy assessments (biomarkers) and disease progression (RECIST imaging) will be assessed
every two 28-Day cycles. The subjects will be assessed for safety for at least 28-Days
after the last dose of YN968D1.
For Part 1 of this study, a Dose Limiting Toxicity (DLT) event is defined as any of the
following events that are assessed by the Investigator as probably or possibly related to
YN968D1 and occur during or after the initial dose on Day 1 through Day 35 of the first
cycle of therapy.
- CTCAE Grade 4 event
- Grade 3 febrile neutropenia (<1,000 neutrophils/mL)
- Grade 3 hematologic toxicity with duration > 7 days
- Grade 3 non-hematologic toxicity (except for nausea, vomiting, diarrhea that continues
despite optimal medical management)
If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If two
(2) DLTs are experienced in any cohort, the study will be paused until the safety events are
evaluated and discussed with the FDA to determine if the trial may continue.
Part 2 of this study will include up to 30 subjects. Each subject will receive a 750 mg
dose or the maximum tolerated dose of YN968D1 from part 1 of the study for continuous 28-Day
cycles of therapy. If a subject experiences an intolerable side effect a dose reduction or a
dose interruption for up to 7-Days is allowed at the discretion of the investigator.
Subjects will be evaluated for RECIST (version 1.1) response at the end of the second cycle
of therapy on Day 56±3 of the Part 2 study. Safety reporting will be continued for 28-Days
from the last dose of study medication.
All subjects in Part 1 and 2 of this trial will be eligible to continue therapy provided
they have a least stable disease or better and are, in the opinion of the investigator,
adequately tolerating treatment with YN968D1.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety in the first 28-Days of Therapy
The primary endpoint is evaluation of safety during the first 28-day cycle of therapy following the initiation of multiple dosing of YN968D1. The safety variables to be evaluated in this study are adverse events, physical examinations, vital signs (specifically including blood pressure), clinical laboratory evaluations including serum chemistry, hematology (including RBC morphology and reticulocyte count), and urinalysis (with detailed sediment analysis, proteinuria, and 24-hour urine for collection for creatinine clearance and protein), and electrocardiograms (ECGs) in triplicate.
28-Days after Discontinuation of YN968D1
Sunil Sharma, MD, FACP
Huntsman Cancer Institute
United States: Food and Drug Administration
|Huntsman Cancer Institute||Salt Lake City, Utah 84112|