A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Spartalizumab; Placebo; Dabrafenib; Trametinib
Intervention description: Spartalizumab powder for solution is used in Part 1 and Part 2, and as concentrate for solution for infusion for Part 3. Spartalizumab is administered via intravenous infusion over 30 minutes once every 4 weeks; Placebo is administered via intravenous infusion over 30 minutes once every 4 weeks; Dabrafenib 150 mg capsules BID is administered orally for Days 1-28 of a 28-day cycle, in fasting conditions.; Trametinib 2 mg tablets QD is administered orally for Days 1-28 of a 28-day cycle, in fasting conditions
Intervention MeSH terms: Trametinib; Dabrafenib; Spartalizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Part 1 and Part 2 are open- label. Part 3 is double-blind and randomized.
Enrollment: 568.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Spartalizumab (PDR001); dabrafenib; trametinib; melanoma; immunotherapy; PD 1 inhibitor; anti PD1; PD-1; anti-PD-1; combination treatment; malignant skin cancer; skin cancer; BRAF V600; unresectable BRAF V600 mutated melanoma; metastatic BRAF V600 mutated melanoma

Summary:

      To evaluate the safety and efficacy of the combination of an anti-PD-1 antibody
      (Spartalizumab (PDR001)), a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) in
      unresectable or metastatic BRAF V600 mutant melanoma
    

Eligibility 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

          -  Measurable disease according to RECIST 1.1

          -  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

          -  Measurable disease according to RECIST 1.1

          -  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

          -  Measurable disease according to RECIST 1.1

        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

          -  Neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months prior to
             enrollmen

          -  Radiation therapy within 4 weeks prior to start of study treatment

          -  Active autoimmune disease, and/or history of autoimmune disease(s) that required
             treatment

        Parts 2 & 3: Biomarker cohort & double-blind, randomized, placebo-controlled part

          -  Subjects with uveal or mucosal melanoma

          -  Prior systemic anti-cancer treatment for unresectable or metastatic melanoma

          -  Neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months prior to
             enrollment

          -  Radiation therapy within 4 weeks prior to start of study treatment

          -  Clinically active cerebral melanoma metastasis.

          -  Active autoimmune disease, and/or history of autoimmune disease(s) that required
             treatment

        Other protocol-defined Inclusion/Exclusion may apply.