This is an open-label, non-controlled study conducted in two parts - Part A (dose escalation) followed by Part B (dose expansion).
Patients in Part A will have previously treated progressive or metastatic NSCLC, pancreatic, or colorectal cancer, with or without KRAS mutation. Five dose levels will be explored. In dose level 5, only patients with previously-treated NSCLC with KRAS mutation will be included. Patients in Part B must have previously treated NSCLC with confirmed KRAS mutation. Two dose levels will be explored further in Part B. Twenty (20) patients will be enrolled in Part B, with 10 patients enrolled in each of the two cohorts. Once dose level 5 has been confirmed to be safe in Part A (i.e. 0-1 DLT in 6 patients), an additional 4 patients will then be enrolled for a planned total of 24 patients in Part B.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
49
Intravenous infusion, once-weekly x 4 consecutive weeks, every 6 weeks
Beverly Hills Cancer Center
Beverly Hills, California, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
Moffitt Cancer Center
Tampa, Florida, United States
University of Toledo, Eleanor N. Dana Cancer Center
Number of patients with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: Change in the incidence and severity of adverse events related to study treatment from baseline to 4 weeks following last dose
Best Overall Response per RECIST 1.1
The rate of complete remission (CR) + partial remission (PR) + stable disease (SD)
Time frame: Number of days from date of first dose to 30 days after last treatment
Pharmacokinetic parameters for siRNA
Peak Plasma Concentration (Cmax)
Time frame: Up to 72 hours from start of infusion on Cycle 1, Day 1 and Day 22 and prior to infusion Cycle 1, Day 8 and Cycle 2, Day 1
Additional pharmacokinetic parameters for siRNA
Area under the plasma concentration versus time curve (AUC)
Time frame: Up to 72 hours from start of infusion on Cycle 1, Day 1 and Day 22 and prior to infusion Cycle 1, Day 8 and Cycle 2, Day 1
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