A randomized, double-blind, placebo-controlled, phase III study comparing the combination of PDR001, dabrafenib and trametinib versus placebo, dabrafenib and trametinib in previously untreated patients with unresectable or metastatic BRAF V600 mutant melanoma
- Conditions
- Melanoma1002765610040900
- Registration Number
- NL-OMON54792
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety Run in Part<br /><br>• Incidence of DLTs during the first 8 weeks of treatment for each dose level<br /><br>associated with administration of PDR001 in combination of dabrafenib and<br /><br>trametinib.<br /><br><br /><br><br /><br>Biomarker:<br /><br>• Descriptive statistics of immune microvenvironment and biomarker modulation<br /><br>values and changes from baseline by visit<br /><br><br /><br>Randomized part:<br /><br>• Investigator assessed PFS (according to RECIST 1.1)</p><br>
- Secondary Outcome Measures
Name Time Method <p>part 1<br /><br>• Safety: Incidence and severity of AEs and SAEs, including changes in<br /><br>laboratory values, ECOG PS, vital signs, liver and cardiac parameters.<br /><br>• Tolerability: Dose interruptions, reductions, and dose intensity<br /><br>• PFS, OS, ORR, DOR, DCR by investigator*s assessment according to RECIST 1.1<br /><br><br /><br>Part 2:<br /><br>none<br /><br><br /><br>Part 3<br /><br>• ORR, DOR and DCR by investigator*s assessment according to RECIST 1.1<br /><br>• Safety: Incidence and severity of AEs and SAEs, including changes in<br /><br>laboratory values, ECOG PS, vital signs, liver assessments and cardiac<br /><br>assessments.<br /><br>• Tolerability: Dose interruptions, reductions, and dose intensity<br /><br>• Change from baseline in EORTC QLQ-C30, EQ-5D, and FACT-M melanoma subscale</p><br>