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A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma

NCT02967692

Description:

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

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: CPDR001F2301
  • SECONDARY ID: 2016-002794-35
  • NCT ID: NCT02967692

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
Spartalizumab (PDR001)Investigational treatment arm
DabrafenibTafinlar®Investigational treatment arm
TrametinibMekinist®Investigational treatment arm

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Investigational treatment armExperimentalPart 1: Safety run-in Up to 18 evaluable patients with previously untreated unresectable or metastatic BRAF V600 mutated melanoma will be enrolled and treated at different dose levels to determine the recommended Phase 3 regimen of PDR001 in combination with dabrafenib and trametinib. Part 2: Biomarker cohort Approximately 20 patients with previously unresectable or metastatic BRAF V600 mutated melanoma will be enrolled to describe changes in the immune microenvironment and biomarker modulations Part 3: Randomized double blind Approximately 500 patients with previously untreated unresectable and metastatic BRAF V600 mutated melanoma will be enrolled to compare the anti-tumor activity of PDR001 in combination with dabrafenib and trametinib versus placebo plus dabrafenib and trametinib.
  • Spartalizumab (PDR001)
  • Dabrafenib
  • Trametinib
Placebo comparator armPlacebo ComparatorMatching placebo in combination with dabrafenib and trametinib
  • Dabrafenib
  • Trametinib

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

          -  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

          -  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, placebo-controlled 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

        Other protocol-defined Inclusion/Exclusion may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety Run-In (Part 1): Incidence of dose limiting toxicities (DLTs)
Time Frame:8 weeks
Safety Issue:
Description:Incidence of DLTs during the first 8 weeks of treatment with Spartalizumab (PDR001) in combination of dabrafenib and trametinib

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Up to death due to any cause (5 years)
Safety Issue:
Description:Overall survival is defined as the time from date of randomization to date of death due to any cause
Measure:Overall response rate
Time Frame:Up to disease progression or death due to any cause, whichever occurs first (5 years)
Safety Issue:
Description:ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1
Measure:Duration of response
Time Frame:Up to disease progression or death due to any cause, whichever occurs first (5 years)
Safety Issue:
Description:Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death, according to RECIST 1.1 criteria
Measure:Disease control rate
Time Frame:Up to disease progression or death due to any cause, whichever occurs first (5 years)
Safety Issue:
Description:Disease control rate is defined as the proportion of patients with CR or PR or subjects with SD lasting for a duration of at least 24 weeks as per local review according to RECIST 1.1 criteria
Measure:Global health status/quality of life score of the EORTC QLQ-C30
Time Frame:Up to 60 days post progression (5 years)
Safety Issue:
Description:Patient's health-related quality of life
Measure:Global health status/quality of life score of the FACT-M subscale
Time Frame:Up to 60 days post progression (5 years)
Safety Issue:
Description:Patient's health-related quality of life
Measure:Global health status/quality of life score of the EQ-5D-5L
Time Frame:Up to 60 days post progression (5 years)
Safety Issue:
Description:Patient's health-related quality of life
Measure:Time to 10 point definitive deterioration in overall quality of life score from EORTC QLQ-C30
Time Frame:Up to 60 days post progression (5 years)
Safety Issue:
Description:Patient's health-related quality of life
Measure:PFS by PD-L1 expression
Time Frame:Up to disease progression or death due to any cause, whichever occurs first (5 years)
Safety Issue:
Description:PFS analysis will be performed by PD-L1 subgroup (positive, negative) where a positive status is defined as having ≥ 1% expression and a negative status is defined as having < 1% expression. Additionally PD-L1 subgroups will also be assessed using defined by a PD-L1 expression level cut-off of 10%, where a positive status is defined as having ≥ 10% expression and a negative status is defined as having < 10% expression.
Measure:OS by PD-L1 expression
Time Frame:Up to disease progression or death due to any cause, whichever occurs first (5 years)
Safety Issue:
Description:OS analysis will be performed by PD-L1 subgroup (positive, negative) where a positive status is defined as having ≥ 1% expression and a negative status is defined as having < 1% expression. Additionally PD-L1 subgroups will also be assessed using defined by a PD-L1 expression level cut-off of 10%, where a positive status is defined as having ≥ 10% expression and a negative status is defined as having < 10% expression.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial 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

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