Melanoma
Conditions
Interventions
All participant will be treated with :
Dabrafenib, oral, 150mg BID
Trametinib, oral, 2 mg QD
Biomarker part 
Combination with dabrafenib and trametinib and PDR001 infusion 400mg. Depending 
of the recommended dose in the safety part, it is expected that this infusion 
will be either once every 4 weeks, or once every 8 weeks.
randomized part 
Arm 1: PDR001 infusion in combination with trametinib and dabrafenib
>
Arm 2: placebo in combination with dabrafenib and trametinib
Sponsors
Novartis
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Part 1: Safety run-in • Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation • Aspartate transaminase (AST) < 2.5× ULN and Alanine transaminase (ALT) < 2.5× ULN • ECOG performance status <= 1 Part 2: Biomarker cohort • Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation • At least two cutaneous or subcutaneous or nodal lesions for tumor sample collection • ECOG performance status <= 2 Part 3: Double-blind, randomized, placebo-controlled part • Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation • ECOG performance status <= 2
Exclusion criteria
Exclusion criteria: Part 1: Safety run-in • Subjects with uveal or mucosal melanoma • Any history of CNS metastases • Prior systemic anti-cancer treatment for unresectable or metastatic melanoma • Prior loco-regional treatment for unresectable or metastatic melanoma in the last 6 month • Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months • Radiation therapy within 4 weeks prior to start of study treatment • Active, known, suspected or a documented history of autoimmune disease, Parts 2 & 3: Biomarker cohort & double-blind, randomized, placebocontrolled part • Subjects with uveal or mucosal melanoma •Clinically active cerebral melanoma metastasis • Prior systemic anti-cancer treatment for unresectable or metastatic melanoma • Prior loco-regional treatment for unresectable or metastatic melanoma in the last 6 month • Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months • Radiation therapy within 4 weeks prior to start of study treatment • Active, known, suspected or a documented history of autoimmune disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Run in Part • Incidence of DLTs during the first 8 weeks of treatment for each dose level associated with administration of PDR001 in combination of dabrafenib and trametinib. Biomarker: • Descriptive statistics of immune microvenvironment and biomarker modulation values and changes from baseline by visit Randomized part: • Investigator assessed PFS (according to RECIST 1.1) | — |
Secondary
| Measure | Time frame |
|---|---|
| part 1 • Safety: Incidence and severity of AEs and SAEs, including changes in laboratory values, ECOG PS, vital signs, liver and cardiac parameters. • Tolerability: Dose interruptions, reductions, and dose intensity • PFS, OS, ORR, DOR, DCR by investigator*s assessment according to RECIST 1.1 Part 2: none Part 3 • ORR, DOR and DCR by investigator*s assessment according to RECIST 1.1 • Safety: Incidence and severity of AEs and SAEs, including changes in laboratory values, ECOG PS, vital signs, liver assessments and cardiac assessments. • Tolerability: Dose interruptions, reductions, and dose intensity • Change from baseline in EORTC QLQ-C30, EQ-5D, and FACT-M melanoma subscale | — |
Countries
Netherlands
Outcome results
None listed