Study of safety and efficacy of PDR001 in combination with dabrafenib and trametinib in patients with a genetically distinct subtype of unresectable or metastatic melanoma, which is characterised by a mutation in the BRAF gene

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

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-002794-35-DE

Enrollment

538

Registered

2016-11-29

Start date

2017-02-20

Completion date

Unknown

Last updated

2024-10-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Unresectable or metastatic BRAF V600 mutant melanoma MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864

Interventions

Trade Name: Mekinist Product Name: Mekinist Product Code: TMT212 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: trametinib CAS Number: 1187431-43-1 Current Sponsor code: TMT212 Other des

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Part 1: Safety run-in •Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation •Aspartate transaminase (AST) =65 years) yes F.1.3.1 Number of subjects for this age range 129

Exclusion criteria

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, 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 Other protocol-defined Exclusion may apply.

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 PD-L1 levels and CD8+ cells 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: Key secondary 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 Other secondary Part 1&2: Safety run-in and biomarker cohort •To evaluate preliminary anti-tumor activity of 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 ORR, DCR, DOR per investigator's assessment according to RECIST 1.1 • To evaluate patient reported outcomes of PDR001 in combination with dabrafenib and trametinib versus placebo plus dabrafenib and trametinib •To characterize the potential for PD-L1 expression to identify subjects with an enhanced response to PDR001 in combination with dabrafenib and trametinib versus placebo plus dabrafenib and trametinib;Primary end point(s): Part 1: Safety run-in; Incidence of dose limiting toxicities (DLTs) • Incidence of DLTs during the first 8 weeks of treatment with PDR001 in combination of dabrafenib and trametinib. Part 2: Biomarker cohort; Immune microenvironment and biomarker modulation • Changes in PD-L1 levels and CD8+ cells upon treatment with PDR001 in combination with dabrafenib and trametinib Part 3: Pro	—

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 PD-L1 levels and CD8+ cells 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: Key secondary 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 Other secondary Part 1&2: Safety run-in and biomarker cohort •To evaluate preliminary anti-tumor activity of 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 ORR, DCR, DOR per investigator's assessment according to RECIST 1.1 • To evaluate patient reported outcomes of PDR001 in combination with dabrafenib and trametinib versus placebo plus dabrafenib and trametinib •To characterize the potential for PD-L1 expression to identify subjects with an enhanced response to PDR001 in combination with dabrafenib and trametinib versus placebo plus dabrafenib and trametinib;Primary end point(s): Part 1: Safety run-in; Incidence of dose limiting toxicities (DLTs) • Incidence of DLTs during the first 8 weeks of treatment with PDR001 in combination of dabrafenib and trametinib. Part 2: Biomarker cohort; Immune microenvironment and biomarker modulation • Changes in PD-L1 levels and CD8+ cells upon treatment with PDR001 in combination with dabrafenib and trametinib Part 3: Pro

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Secondary

Measure	Time frame
Secondary end point(s): 1.Overall survival (OS) OS is defined as the time from date of randomization to date of death due to any cause 2.Overall response rate (ORR) 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 3.Duration of response (DOR) DOR 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 4.Disease control rate (DCR) DCR 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 5.Global health status/quality of life score of the EORTC QLQ-C30 Patient's health-related quality of life 6.Global health status/quality of life score of the FACT-M subscale Patient's health-related quality of life 7.Global health status/quality of life score of the EQ-5D-5L Patient's health-related quality of life 8.Time to 10 point definitive deterioration in overall quality of life score from EORTC QLQ-C30 Patient's health-related quality of life 9.PFS by PD-L1 expression 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. 10.OS by PD-L1 expression 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	—

Measure

Time frame

Secondary end point(s): 1.Overall survival (OS) OS is defined as the time from date of randomization to date of death due to any cause 2.Overall response rate (ORR) 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 3.Duration of response (DOR) DOR 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 4.Disease control rate (DCR) DCR 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 5.Global health status/quality of life score of the EORTC QLQ-C30 Patient's health-related quality of life 6.Global health status/quality of life score of the FACT-M subscale Patient's health-related quality of life 7.Global health status/quality of life score of the EQ-5D-5L Patient's health-related quality of life 8.Time to 10 point definitive deterioration in overall quality of life score from EORTC QLQ-C30 Patient's health-related quality of life 9.PFS by PD-L1 expression 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. 10.OS by PD-L1 expression 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

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Countries

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czechia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

Public ContactMedizinischer Infoservice (MCC)

Novartis Pharma GmbH

infoservice.novartis@novartis.com+4991127312100

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026