advanced or metastatic BRAF V600
Conditions
Interventions
Dabrafenib (DRB436), LTT462, trametinib (TMT212), LXH254, TNO155, spartalizumab
(PDR001), tislelizumab (VDT482) in various combinations.
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients must be >= 18 years of age. ECOG performance status
Exclusion criteria
Exclusion criteria: Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs Patients with CNS tumor involvement, unless > 2 weeks after completion of CNS-therapy, stable with respect to CNS-involvement, not receiving steroids or on stable dose of 1.5 x upper limit of normal (ULN), Asparate aminotransferase (AST) > 3 x ULN Alanine aminotransferase (ALT) > 3 x ULN Serum creatinine > 1.5 x ULN OR Creatinine Clearance
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, and ECGs Incidence and nature of DLTs in the first cycle (dose escalation only) Dose interruptions, reductions, and dose intensity | — |
Secondary
| Measure | Time frame |
|---|---|
| Tumor MAPK pathway suppression (change from baseline) within combination treatment arms Tumor mutational changes throughout treatment course Tumor immune phenotyping within combination treatment arms (e.g. CD8, PD-L1) BOR per RECIST v1.1 For individual investigational drug, compare the PK in combination regimen vs. as a single agent | — |
Countries
Netherlands
Outcome results
None listed