Clinical Trial 19474

Cancer Type:
Interventions:GSK1120212 (Trametinib); GSK2118436 (dabrafenib); PDR001; Placebo; Trametinib; dabrafenib

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Nikhil Khushalani

Overview

Study Title

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

Summary

The purpose of this study is to evaluate the safety and efficacy of the combination of an anti-PD-1 antibody (PDR001), a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) in unresectable or metastatic BRAF V600 mutant melanoma.

Objective

To determine the recommended regimen of PDR001 in combination with dabrafenib and trametinib for the randomized part. To evaluate changes in PD-L1 levels and CD8+ cells upon treatment with PDR001 in combination with 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 PFS per investigators assessment according to RECIST 1.1.

Inclusion Criteria

  • PART 1 - SAFETY RUN-IN: Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation; Aspartate transaminase (AST) less than 2.5× upper limit of normal (ULN) and Alanine transaminase (ALT) less than 2.5× ULN; Eastern Cooperative Oncology Group (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

  • PART 1 - SAFETY RUN-IN: Uveal or mucosal melanoma; Any history of central nervous system (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 months; 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 AND 3 - BIOMARKER COHORT AND DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PART: 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 months; 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.
  • Other protocol-defined Inclusion/Exclusion may apply.