Primary Outcome Measures
Safety and tolerability as assessed by incidence and severity of adverse events (AEs), dose interruptions, reductions, and dose intensity. [Time Frame: From Cycle 1 Day 1 until 30 days for LXH254 single agent and 150 days for LXH254 in combination with PDR001 post study treatment (expected duration approximately 12 months)] [Designated as safety issue: ]
Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 single agent only) [Time Frame: 28 days] [Designated as safety issue: ]
Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 in combination with PDR001 only) [Time Frame: 56 days] [Designated as safety issue: ]
Secondary Outcome Measures
Overall response rate (ORR) [Time Frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months] [Designated as safety issue: ]
Disease control rate (DCR) [Time Frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months] [Designated as safety issue: ]
Duration of response (DoR) [Time Frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months] [Designated as safety issue: ]
Progression-free survival (PFS) [Time Frame: Every 2 cycles after starting study treatment until disease progression; expected duration approximately 12 months] [Designated as safety issue: ]
Overall survival (OS) - only for dose expansion [Time Frame: From time of start treatment until the date of death; expected duration approximately 12 months] [Designated as safety issue: ]
Plasma concentrations of LXH254 [Time Frame: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1] [Designated as safety issue: ]
Derived PK parameters of LXH254: Area Under the Curve (AUC) [Time Frame: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1] [Designated as safety issue: ]
Derived PK parameters of LXH254: Peak Plasma Concentration (Cmax) [Time Frame: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1] [Designated as safety issue: ]
Derived PK parameters of LXH254: Time to Peak Plasma Concentration (Tmax) [Time Frame: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1] [Designated as safety issue: ]
Derived PK parameters of LXH254: half-life (T1/2) [Time Frame: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1] [Designated as safety issue: ]
Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor tissue and in blood [Time Frame: Cycle 1 day 1, 2, 3, 15, and 16; upon disease progression (expected duration approximately 12 months)] [Designated as safety issue: ]
Plasma concentrations of PDR001 [Time Frame: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1] [Designated as safety issue: ]
Derived PK parameters of PDR001: Area Under the Curve (AUC) [Time Frame: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1] [Designated as safety issue: ]
Derived PK parameters of PDR001: Peak Plasma Concentration (Cmax) [Time Frame: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1] [Designated as safety issue: ]
Derived PK parameters of PDR001: Time to Peak Plasma Concentration (Tmax) [Time Frame: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1] [Designated as safety issue: ]
Derived PK parameters of PDR001: half-life (T1/2) [Time Frame: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1] [Designated as safety issue: ]