A phase Ib, open-label platform study of select drug combinations chosen in order to characterize safety and tolerability of each treatment arm tested and to identify recommended doses and regimens for future studies.
This is a phase Ib, multi-center, open-label study with multiple treatment arms in adult patients with advanced or metastatic BRAF V600 (E, D, or K) in order to characterize safety and tolerability of each treatment arm tested and to identify recommended doses and regimens for future studies. The open platform design of this study is adaptive to allow removal of combination treatment arm(s) based on emerging data and facilitate introduction of new candidate combinations. The study is comprised of a dose escalation part and may be followed by a dose expansion part for any combination treatment arm.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
122
University of California LA Santa Monica Location
Los Angeles, California, United States
Massachusetts General Hospital Massachusetts General Hospital
Boston, Massachusetts, United States
Incidence and nature of dose limiting toxicities (DLTs) in the first cycle
To characterize safety and tolerability of each treatment arm tested and identify recommended doses (RD) and regimens for future studies
Time frame: 30 months
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, and ECGs
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Time frame: 34 months
Frequency of dose interruptions
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Time frame: 30 months
Frequency of dose reductions
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Time frame: 30 months
Dose intensity
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Time frame: 30 months
AUClast derived from Serum/plasma concentration of individual investigational drugs within combination treatments
To characterize the PK of each investigational drug within each treatment arm
Time frame: 30 months
Best overall response (BOR)
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Tablet for oral use
Capsule for oral use
Liquid in vial (Concentrate for solution for infusion) for intravenous use
Liquid in vial (Concentrate for solution for infusion) for intravenous use
Sarah Cannon Research Institute SC
Nashville, Tennessee, United States
Uni Of TX MD Anderson Cancer Cntr
Houston, Texas, United States
Novartis Investigative Site
Westmead, New South Wales, Australia
Novartis Investigative Site
Brussels, Belgium
Novartis Investigative Site
Leuven, Belgium
Novartis Investigative Site
Toronto, Ontario, Canada
Novartis Investigative Site
Dresden, Germany
Novartis Investigative Site
Essen, Germany
...and 8 more locations
Time frame: 34 months
Progression free survival (PFS)
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Time frame: 34 months
Overall response rate (ORR)
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Time frame: 34 months
Duration of response (DOR)
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Time frame: 34 months
Disease control rate (DCR)
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Time frame: 34 months
Change from baseline of the PD marker DUSP6 in tumor tissue (dose escalation only)
To evaluate PD effect in their respective combinations in tumor
Time frame: 30 months
AUCtau derived from Serum/plasma concentration of individual investigational drugs within combination treatments
To characterize the PK of each investigational drug within each treatment arm
Time frame: 30 months
Cmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments
To characterize the PK of each investigational drug within each treatment arm
Time frame: 30 months
Tmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments
To characterize the PK of each investigational drug within each treatment arm
Time frame: 30 months