This study was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of LXS196 as a single agent and in combination with HDM201 in patients with metastatic uveal melanoma.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
107
LXS196 as a single agent
LXS196 in combination with HDM201
Columbia University Medical Center
New York, New York, United States
Novartis Investigative Site
Westmead, New South Wales, Australia
Novartis Investigative Site
Paris, France
Novartis Investigative Site
Leiden, Netherlands
Incidence of dose limiting toxicities (DLTs) (Dose escalation only)
cycle = 28 days
Time frame: Cycle 1 in dose escalation
Incidence and severity of adverse events and serious adverse events, including changes in laboratory parameters, vital signs and ECGs graded as per NCI CTCAE version 4.03 (All patients)
Time frame: Continuously throughout the study until 30 days after treatment discontinuation
Dose interruptions, reductions and dose intensity
Time frame: Continuously throughout the study until 30 days after treatment discontinuation
Overall response rate (ORR) per RECIST version 1.1 criteria
Time frame: From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months
Plasma LXS196 concentration-time profiles as a single agent
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Modulation of signaling molecules downstream of PKC
Time frame: Baseline and Cycle 1 Day 15
Progression free survival (PFS) per RECIST version 1.1 criteria
Time frame: From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months
Plasma PK parameters of LXS196 as a single agent:AUC
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: Cmax
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Novartis Investigative Site
Oslo, Norway
Novartis Investigative Site
Madrid, Spain
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: Tmax
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: t1/2
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: Racc
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma HDM201 concentration-time profiles
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: AUC
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: Cmax
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: Tmax
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: t1/2
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma LXS196 concentration-time profiles in combination with HDM201
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201:AUC
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: Cmax
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: Tmax
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: t1/2
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: Racc
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
LXS196 plasma protein binding as a single agent
Time frame: Cycle 1 Day 1, 2, 15, 16
LXS196 plasma protein content as a single agent
Time frame: Cycle 1, 2, 3 and 4 Day 1