Unresectable or metastatic BRAF V600 mutant melanoma MedDRA version: 19.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation • Measurable disease according to RECIST 1.1 • ECOG performance status = 1 (part 1: safety run-in), = 2 (part 2: biomarker cohort and part 3: randomized part) • Left ventricular ejection fraction (LVEF) = lower limit of institutional normal (LLN) • At least two cutaneous or subcutaneous lesions or nodal lesions for tumor sample collection (part 2: biomarker cohort ) • Adequate bone marrow and organ function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 409 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 129
Exclusion criteria
Exclusion criteria: • Any history of CNS metastases (part 1: safety run-in) • Clinically active cerebral melanoma metastasis (part 2: biomarker cohort and part 3: randomized part) • Subjects with uveal or mucosal melanoma • Prior systemic anticancer therapy for unresectable or metastatic melanoma • Neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months prior to enrollment • Radiotherapy within 4 weeks prior to the first dose of study treatment • Uncontrolled infections • Active autoimmune disease, and/or history of autoimmune disease(s) that required treatment • Known history of prior or current retinal vein occlusion (RVO)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: Safety run-in To determine the recommended regimen of PDR001 in combination with dabrafenib and trametinib for the randomized part (part 3) Part 2: Biomarker cohort To evaluate changes in the immune microenvironment and biomarker modulations upon treatment with PDR001 in combination with dabrafenib and trametinib Part 3: Double-blind, randomized, placebo-controlled part To compare the anti-tumor activity of PDR001 in combination with dabrafenib and trametinib versus placebo plus dabrafenib and trametinib as measured by PFS per investigator’s assessment according to RECIST 1.1;Secondary Objective: Part 1: Safety run-in To determine safety and tolerability of PDR001 in combination with dabrafenib and trametinib To evaluate preliminary anti-tumor activity of PDR001 in combination with dabrafenib and trametinib To characterize pharmacokinetics (PK) of PDR001, dabrafenib and trametinib when administered in combination To evaluate the prevalence and incidence of immunogenicity Part 3: Double-blind, randomized, placebo-controlled part To compare overall survival of PDR001 in combination with dabrafenib and trametinib versus placebo plus dabrafenib and trametinib To compare the anti-tumor activity of PDR001 in combination with dabrafenib and trametinib versus placebo plus dabrafenib and trametinib as measured by ORR, DCR, DOR per investigator’s assessment according to RECIST 1.1 To evaluate safety and tolerability of PDR001 in combination with dabrafenib and trametinib versus placebo plus dabrafenib and trametinib;Primary end point(s): Part 1: Safety run-in • 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. Part 2: Biomarker cohort • Descriptive statistics of biomarker values and changes from baseline by visit Part 3: Double-blind, randomized, placebo-controlled part • Investigator assessed PFS according to RECIST 1.1;Timepoint(s | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: Safety run-in 1) Safety and tolerability: Incidence and severity of AEs and SAEs, including changes in laboratory values, ECOG PS, vital signs, liver and cardiac parameters, Dose interruptions, reductions, and dose intensity 2) OS PFS, ORR, DOR, DCR by investigator’s assessment according to RECIST 1.1 please refer to protocol for other secondary endpoints Part 3: Double-blind, randomized, placebo-controlled part 1) OS (key secondary), ORR, DOR and DCR by investigator’s assessment according to RECIST 1.1 2) Safety and tolerability: Incidence and severity of AEs and SAEs, including changes in laboratory values, ECOG PS, vital signs, liver and cardiac parameters, dose interruptions, reductions, and dose intensity 3) Change from baseline in EORTC QLQ-C30, EQ-5D, and FACT-M melanoma subscale please refer to protocol for other secondary endpoints;Timepoint(s) of evaluation of this end point: Part 1 Safety Run-in 1) Every study visit and safety FU on days 30, 60, 90, 120 and 150 2) at Cycle 4 Day 1 (± 7 days), then every 8 weeks, until Cycle 22 Day 1 (± 7 days) when frequency will switch to every 12 weeks Part 3: Double-blind, randomized, placebo-controlled part 1) at Cycle 4 Day 1 (± 7 days), then every 8 weeks, until Cycle 22 Day 1 (± 7 days) when frequency will switch to every 12 weeks and Survival FU until Death or lost to FU 2) Every study visit and safety FU on days 30, 60, 90, 120 and 150 3) Baseline, Cycle 3 Day 1, every 8 weeks for the first 12 cycles and every 12 weeks thereafter until confirmed PD, 30 days post PD and 60 days post PD | — |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Colombia, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactDepartamento Médico Oncología (GMO)
Novartis Farmacéutica, S.A.
Outcome results
None listed