search
Back to results

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

Primary Purpose

Melanoma

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Spartalizumab
Placebo
Dabrafenib
Trametinib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • California Cancer Associates for Research and Excellence SC-2
  • UC Irvine Medical Center SC
  • California Pacific Medical Center
  • Stanford Cancer Center SC-2
  • University of Kansas Cancer Center SC
  • Johns Hopkins U SC
  • Nebraska Cancer Specialists
  • NYU Laura and Isaac Perlmutter Cancer Center SC
  • University of Pittsburgh Medical Center SC
  • University of Tennessee Medical Center SC
  • University of TX MD Anderson Cancer Center SC-2
  • Utah Cancer Specialists SC 2
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Kyushu University Hospital
  • Kyoto University Hospital
  • Osaka International Cancer Institute
  • Tokyo Metropolitan Komagome Hospital
  • National Cancer Hospital
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Part 1: Safety run-in Cohort

Part 2: Biomarker cohort

Part 3- Arm 1: Spartalizumab in combination with dabrafenib and trametinib

Part 3- Arm 2: Placebo in combination with dabrafenib and trametinib

Arm Description

In Part 1, participants are treated at different dose levels to determine the recommended Phase 3 regimen of spartalizumab in combination with dabrafenib and trametinib. The starting dose of spartalizumab is 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).

In Part 2, participants are treated with spartalizumab 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).

In Part 3, participants are randomized to receive spartalizumab at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD)

In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD)

Outcomes

Primary Outcome Measures

Safety Run-In (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was defined as an adverse event or abnormal laboratory value that was unrelated to disease, disease progression, inter-current illness, or concomitant medications and occured within 8 weeks of treatment with spartalizumab in combination with dabrafenib and trametinib. The DLT criteria included Grade 4 hematological adverse events, Grade 4 bilirubin elevation, specific gastrointestinal adverse events, symptomatic serum amylase or lipase elevation, Grade 3 or higher hypertension, Grade 3 or higher cardiac events, Grade 2 or higher pneumonitis, Grade 3 or higher immune-related toxicities, infusion-related reactions, other clinically significant adverse events, and toxicities leading to a dosing delay of over 12 weeks. NCI CTCAE v4.03 was used for grading DLTs
Biomarker Cohort (Part 2): Change From Baseline in Programmed Cell Death-ligand 1 (PD-L1) Expression Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib
Change from baseline in PD-L1 expression (as determined by immunohistochemistry in tissue samples) upon treatment with spartalizumab in combination with dabrafenib and trametinib in participants from Part 2
Biomarker Cohort (Part 2): Change From Baseline in CD8+ Cells Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib
Change from baseline in CD8+ cells (as determined by flow cytometry in blood samples) upon treatment with spartalizumab in combination with dabrafenib and trametinib in participants from Part 2
Randomized (Part 3): Progression-Free Survival (PFS) as Per Investigator's Assessment by RECIST 1.1
Progression-free survival was defined as the time from the date of first dose to the date of the first documented radiological progression per investigator's assessment according to RECIST 1.1 or death due to any cause. The distribution of PFS was estimated using the Kaplan-Meier (KM) method. If a patient had not had an event at the time of data cut-off, progression-free survival was censored at the date of last adequate tumor assessment.

Secondary Outcome Measures

Overall Survival (OS)
Overall survival is defined as the time from date of randomization to date of death due to any cause
Overall Response Rate (ORR) as Per Investigator's Assessment by RECIST 1.1
ORR was defined as the percentage of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters
Duration of Response (DOR) as Per Investigator's Assessment by RECIST 1.1
DOR was 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. The distribution of DOR was estimated using the KM method. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters
Disease Control Rate (DCR) as Per Investigator's Assessment by RECIST 1.1
DCR was defined as the percentage of participants with CR or PR or subjects with stable disease (SD) lasting for a duration of at least 24 weeks as per local review according to RECIST 1.1 criteria. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Global Health Status Scores
The EORTC QLQ-C30 was a 30-item questionnaire that patients complete, consisting of both multi-item scales and single-item measures. It included five functional scales, three symptom scales, six single items, and a Global Health Status/Quality of Life (GHS/QoL) scale. The GHS/QoL scale had seven possible response scores ranging from 1 (very poor) to 7 (excellent), which were averaged and transformed to a 0-100 scale. A higher score on this scale indicated a better quality of life. The change from baseline in GHS/QoL scores was calculated. A positive change from baseline indicated improvement in the patient's quality of life.
Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Physical Functioning Scale Scores
The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The EORTC QLQ-C30 physical functioning scale measured a patient's ability to carry out daily activities and tasks requiring physical exertion. It consisted of five questions asking patients to rate their level of physical functioning, with response options ranging from 1="not at all" to 4="very much". The scores for each item were summed and transformed to a 0 to 100 scale, with higher scores indicating better physical functioning. The change from baseline in physical functioning scale scores was calculated. A positive change from baseline indicated improvement in physical functioning.
Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Pain Symptom Scale Scores
The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The EORTC QLQ-C30 pain symptom scale was one of the symptom scales in the questionnaire, which measured the severity of pain experienced by the patient. The pain symptom scale consisted of two items, one measuring the severity of pain and the other measuring the use of painkillers. The items were rated on a 4-point scale ranging from 1="not at all" to 4="very much". The scores for each item were summed and transformed to a 0 to 100 scale, with higher scores indicating more severe pain. The change from baseline in pain symptom scale scores was calculated. A negative change from baseline indicated improvement.
Randomized (Part 3): Time to 10 Point Definitive Deterioration in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Global Health Status
The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The GHS/QoL scale had seven possible response scores ranging from 1 (very poor) to 7 (excellent), which were averaged and transformed to a 0-100 scale. A higher score on this scale indicated a better quality of life. The time to definitive 10 point deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the GHS/QoL score or death due to any cause. If a subject had not had an event, the time to deterioration was censored at the date of the last adequate assessment. The distribution was estimated using KM method.
Randomized (Part 3): Change From Baseline in Function Assessment Cancer Therapy-melanoma (FACT-M) Melanoma Subscale Score
The Functional Assessment of Cancer Therapy-Melanoma (FACT-M) quality of life questionnaire was composed of the FACT-General (FACT-G) plus the Melanoma Subscale and the Melanoma Surgery Subscale, which complemented the general scale with items specific to quality of life (QoL) in melanoma. The Melanoma Subscale of FACT-M included 16 questions, with response options of 0= "Not at all", 1= "a little bit", 2= "somewhat", 3= "quite a bit" and 4= "very much". The FACT-M melanoma subscale score ranged from 0 to 64, with higher scores indicating a higher quality of life in relation to melanoma. The change from baseline in melanoma subscale scores was calculated. A positive change from baseline indicated improvement.
Randomized (Part 3): Change From Baseline in EuroQoL 5-level Instrument (EQ-5D-5L)- Visual Analog Scale (VAS) Score
The EQ-5D-5L is a standardized questionnaire used to assess health-related quality of life, and it includes a Visual Analog Scale (VAS). The VAS score is obtained by asking the individual to rate their current health status on a scale from 0 to 100, where 0 represents the worst possible health state and 100 represents the best possible health state. The change from baseline in EQ-5D-5L VAS score was calculated. A positive change from baseline indicates improvement in the health status.
Randomized (Part 3): PFS as Per Investigator's Assessment by RECIST 1.1 by PD-L1 Expression
PFS was defined as the time from the date of first dose to the date of the first documented radiological progression as per investigator's assessment using RECIST 1.1 response criteria or death due to any cause. The distribution of PFS was estimated using the KM method. If a patient had not had an event at the time of data cut-off, progression-free survival was censored at the date of last adequate tumor assessment. PFS analysis was performed by PD-L1 status (positive, negative) where a positive status was defined as having ≥ 1% expression and a negative status was defined as having < 1% expression.
Randomized (Part 3): OS by PD-L1 Expression
OS is defined as the time from date of randomization to date of death due to any cause. 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.
Spartalizumab Anti-drug Antibody (ADA) Prevalence at Baseline
Spartalizumab ADA prevalence at baseline was calculated as the percentage of participants who had an spartalizumab ADA positive result at baseline.
Spartalizumab ADA Incidence
Spartalizumab ADA incidence was calculated as the percentage of participants who were treatment-induced spartalizumab ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted spartalizumab ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
Trough Concentration (Ctrough) for Spartalizumab
Ctrough for spartalizumab refers to the serum concentration of spartalizumab immediately prior to the administration of a dose of spartalizumab on Day 1 of Cycle 2 and later cycles.
Pre-dose Plasma Concentration for Dabrafenib
Plasma concentration of dabrafenib immediately prior to the administration of a dose of dabrafenib.
Pre-dose Plasma Concentration for Trametinib
Plasma concentration of trametinib immediately prior to the administration of a dose of trametinib.
Number of Participants With Dose Interruptions
Number of participants with dose interruptions for spartalizumab, dabrafenib and trametinib
Number of Participants With Dose Reductions
Number of patients with dose reductions for spartalizumab, dabrafenib and trametinib
Relative Dose Intensity
Relative dose intensity for spartalizumab, dabrafenib and trametinib computed as the ratio of dose intensity and planned dose intensity

Full Information

First Posted
November 16, 2016
Last Updated
October 2, 2023
Sponsor
Novartis Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT02967692
Brief Title
A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma
Acronym
COMBI-i
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 17, 2017 (Actual)
Primary Completion Date
August 11, 2020 (Actual)
Study Completion Date
March 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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
Detailed Description
This study is designed as a Phase III, multi-center study consisting of three parts: Part 1, known as the Safety Run-in, is an open-label part aimed at determining the recommended Phase III regimen (RP3R) of spartalizumab in combination with dabrafenib and trametinib for previously untreated subjects with BRAF V600 mutant unresectable or metastatic melanoma (Stage IIIC/IV per AJCC edition 7). In Part 1, spartalizumab was administered at a starting dose level (DL1) of 400 mg every 4 weeks (Q4W), along with fixed doses of dabrafenib (150 mg twice daily) and trametinib (2 mg once daily). The RP3R for Part 3 was determined using the Bayesian Logistic Regression Model (BLRM) with escalation with overdose control (EWOC) criteria. Part 2, referred to as the Biomarker Cohort, is an open-label section focused on characterizing the kinetics of immune biomarkers and potential immune resistance mechanisms. Part 2 started when the fourth subject in dose level 1 (DL1) of Part 1 completed approximately 4 weeks of study treatment, and fewer than 3 dose-limiting toxicities (DLTs) were observed. Participants in Part 2 receive PDR001 (spartalizumab) at a dosage of 400 mg Q4W, in combination with dabrafenib (150 mg BID) and trametinib (2 mg QD). Part 3 is a double-blind, randomized, placebo-controlled phase that compares the efficacy and safety of spartalizumab in combination with dabrafenib and trametinib to placebo in combination with dabrafenib and trametinib. Part 3 was initiated after determining the RP3R for the combination of spartalizumab with dabrafenib and trametinib in Part 1. Subjects were randomized in a 1:1 ratio to receive either the RP3R dose of spartalizumab identified in Part 1 or placebo, along with dabrafenib (150 mg BID) and trametinib (2 mg QD). For all parts of the study, the treatment is continued until the subject experiences any of the following events: disease progression according to RECIST 1.1 as determined by the Investigator, unacceptable toxicity, initiation of a new anti-neoplastic therapy, pregnancy, withdrawal of consent, physician's decision, loss to follow-up, death, or termination of the study by the Sponsor. Safety evaluations are conducted for all subjects for up to 150 days after the last dose of spartalizumab/placebo (safety follow-up period). Subjects who discontinue study treatment without disease progression as per RECIST 1.1 continue with tumor assessments according to the protocol until documented disease progression, withdrawal of consent, loss to follow-up, or death, regardless of the initiation of new anti-neoplastic therapy (efficacy follow-up period). Subjects enter the survival follow-up period after completing the safety follow-up period or experiencing disease progression as per RECIST 1.1 or response criteria for immunotherapy, whichever period is longer (survival follow-up period).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Part 1 and Part 2 are open- label. Part 3 is double-blind and randomized.
Allocation
Randomized
Enrollment
569 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Safety run-in Cohort
Arm Type
Experimental
Arm Description
In Part 1, participants are treated at different dose levels to determine the recommended Phase 3 regimen of spartalizumab in combination with dabrafenib and trametinib. The starting dose of spartalizumab is 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).
Arm Title
Part 2: Biomarker cohort
Arm Type
Experimental
Arm Description
In Part 2, participants are treated with spartalizumab 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).
Arm Title
Part 3- Arm 1: Spartalizumab in combination with dabrafenib and trametinib
Arm Type
Experimental
Arm Description
In Part 3, participants are randomized to receive spartalizumab at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD)
Arm Title
Part 3- Arm 2: Placebo in combination with dabrafenib and trametinib
Arm Type
Placebo Comparator
Arm Description
In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD)
Intervention Type
Biological
Intervention Name(s)
Spartalizumab
Other Intervention Name(s)
PDR001
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
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo is administered via intravenous infusion over 30 minutes once every 4 weeks
Intervention Type
Drug
Intervention Name(s)
Dabrafenib
Intervention Description
Dabrafenib 150 mg capsules BID is administered orally for Days 1-28 of a 28-day cycle, in fasting conditions.
Intervention Type
Drug
Intervention Name(s)
Trametinib
Intervention Description
Trametinib 2 mg tablets QD is administered orally for Days 1-28 of a 28-day cycle, in fasting conditions
Primary Outcome Measure Information:
Title
Safety Run-In (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs)
Description
DLT was defined as an adverse event or abnormal laboratory value that was unrelated to disease, disease progression, inter-current illness, or concomitant medications and occured within 8 weeks of treatment with spartalizumab in combination with dabrafenib and trametinib. The DLT criteria included Grade 4 hematological adverse events, Grade 4 bilirubin elevation, specific gastrointestinal adverse events, symptomatic serum amylase or lipase elevation, Grade 3 or higher hypertension, Grade 3 or higher cardiac events, Grade 2 or higher pneumonitis, Grade 3 or higher immune-related toxicities, infusion-related reactions, other clinically significant adverse events, and toxicities leading to a dosing delay of over 12 weeks. NCI CTCAE v4.03 was used for grading DLTs
Time Frame
Up to 8 weeks (Part 1)
Title
Biomarker Cohort (Part 2): Change From Baseline in Programmed Cell Death-ligand 1 (PD-L1) Expression Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib
Description
Change from baseline in PD-L1 expression (as determined by immunohistochemistry in tissue samples) upon treatment with spartalizumab in combination with dabrafenib and trametinib in participants from Part 2
Time Frame
Baseline, Cycle 1 Day 15 and Cycle 3 Day 1 (Part 2). Each cycle is 28 days
Title
Biomarker Cohort (Part 2): Change From Baseline in CD8+ Cells Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib
Description
Change from baseline in CD8+ cells (as determined by flow cytometry in blood samples) upon treatment with spartalizumab in combination with dabrafenib and trametinib in participants from Part 2
Time Frame
Baseline, Cycle 1 Day 15 and Cycle 3 Day 1 (Part 2). Each cycle is 28 days
Title
Randomized (Part 3): Progression-Free Survival (PFS) as Per Investigator's Assessment by RECIST 1.1
Description
Progression-free survival was defined as the time from the date of first dose to the date of the first documented radiological progression per investigator's assessment according to RECIST 1.1 or death due to any cause. The distribution of PFS was estimated using the Kaplan-Meier (KM) method. If a patient had not had an event at the time of data cut-off, progression-free survival was censored at the date of last adequate tumor assessment.
Time Frame
Up to disease progression or death due to any cause, whichever occurs first, assessed up to 2.8 years (Part 3)
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall survival is defined as the time from date of randomization to date of death due to any cause
Time Frame
Up to death due to any cause, assessed up to approximately 5 years
Title
Overall Response Rate (ORR) as Per Investigator's Assessment by RECIST 1.1
Description
ORR was defined as the percentage of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters
Time Frame
Part 1: Up to 3.3 years. Part 2: Up to 3 years. Part 3: Up to 2.8 years
Title
Duration of Response (DOR) as Per Investigator's Assessment by RECIST 1.1
Description
DOR was 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. The distribution of DOR was estimated using the KM method. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters
Time Frame
From first documented response to date of first documented progression or death, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3)
Title
Disease Control Rate (DCR) as Per Investigator's Assessment by RECIST 1.1
Description
DCR was defined as the percentage of participants with CR or PR or subjects with stable disease (SD) lasting for a duration of at least 24 weeks as per local review according to RECIST 1.1 criteria. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Time Frame
Part 1: Up to 3.3 years. Part 2: Up to 3 years. Part 3: Up to 2.8 year
Title
Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Global Health Status Scores
Description
The EORTC QLQ-C30 was a 30-item questionnaire that patients complete, consisting of both multi-item scales and single-item measures. It included five functional scales, three symptom scales, six single items, and a Global Health Status/Quality of Life (GHS/QoL) scale. The GHS/QoL scale had seven possible response scores ranging from 1 (very poor) to 7 (excellent), which were averaged and transformed to a 0-100 scale. A higher score on this scale indicated a better quality of life. The change from baseline in GHS/QoL scores was calculated. A positive change from baseline indicated improvement in the patient's quality of life.
Time Frame
From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
Title
Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Physical Functioning Scale Scores
Description
The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The EORTC QLQ-C30 physical functioning scale measured a patient's ability to carry out daily activities and tasks requiring physical exertion. It consisted of five questions asking patients to rate their level of physical functioning, with response options ranging from 1="not at all" to 4="very much". The scores for each item were summed and transformed to a 0 to 100 scale, with higher scores indicating better physical functioning. The change from baseline in physical functioning scale scores was calculated. A positive change from baseline indicated improvement in physical functioning.
Time Frame
From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
Title
Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Pain Symptom Scale Scores
Description
The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The EORTC QLQ-C30 pain symptom scale was one of the symptom scales in the questionnaire, which measured the severity of pain experienced by the patient. The pain symptom scale consisted of two items, one measuring the severity of pain and the other measuring the use of painkillers. The items were rated on a 4-point scale ranging from 1="not at all" to 4="very much". The scores for each item were summed and transformed to a 0 to 100 scale, with higher scores indicating more severe pain. The change from baseline in pain symptom scale scores was calculated. A negative change from baseline indicated improvement.
Time Frame
From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
Title
Randomized (Part 3): Time to 10 Point Definitive Deterioration in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Global Health Status
Description
The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The GHS/QoL scale had seven possible response scores ranging from 1 (very poor) to 7 (excellent), which were averaged and transformed to a 0-100 scale. A higher score on this scale indicated a better quality of life. The time to definitive 10 point deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the GHS/QoL score or death due to any cause. If a subject had not had an event, the time to deterioration was censored at the date of the last adequate assessment. The distribution was estimated using KM method.
Time Frame
From baseline to date of at least 10 points relative to baseline worsening of the global health status score or death due to any cause, up to 2.8 years (Part 3)
Title
Randomized (Part 3): Change From Baseline in Function Assessment Cancer Therapy-melanoma (FACT-M) Melanoma Subscale Score
Description
The Functional Assessment of Cancer Therapy-Melanoma (FACT-M) quality of life questionnaire was composed of the FACT-General (FACT-G) plus the Melanoma Subscale and the Melanoma Surgery Subscale, which complemented the general scale with items specific to quality of life (QoL) in melanoma. The Melanoma Subscale of FACT-M included 16 questions, with response options of 0= "Not at all", 1= "a little bit", 2= "somewhat", 3= "quite a bit" and 4= "very much". The FACT-M melanoma subscale score ranged from 0 to 64, with higher scores indicating a higher quality of life in relation to melanoma. The change from baseline in melanoma subscale scores was calculated. A positive change from baseline indicated improvement.
Time Frame
From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
Title
Randomized (Part 3): Change From Baseline in EuroQoL 5-level Instrument (EQ-5D-5L)- Visual Analog Scale (VAS) Score
Description
The EQ-5D-5L is a standardized questionnaire used to assess health-related quality of life, and it includes a Visual Analog Scale (VAS). The VAS score is obtained by asking the individual to rate their current health status on a scale from 0 to 100, where 0 represents the worst possible health state and 100 represents the best possible health state. The change from baseline in EQ-5D-5L VAS score was calculated. A positive change from baseline indicates improvement in the health status.
Time Frame
From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
Title
Randomized (Part 3): PFS as Per Investigator's Assessment by RECIST 1.1 by PD-L1 Expression
Description
PFS was defined as the time from the date of first dose to the date of the first documented radiological progression as per investigator's assessment using RECIST 1.1 response criteria or death due to any cause. The distribution of PFS was estimated using the KM method. If a patient had not had an event at the time of data cut-off, progression-free survival was censored at the date of last adequate tumor assessment. PFS analysis was performed by PD-L1 status (positive, negative) where a positive status was defined as having ≥ 1% expression and a negative status was defined as having < 1% expression.
Time Frame
Up to disease progression or death due to any cause, up to 2.8 years (Part 3)
Title
Randomized (Part 3): OS by PD-L1 Expression
Description
OS is defined as the time from date of randomization to date of death due to any cause. 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.
Time Frame
Up to death due to any cause, up to 5 years
Title
Spartalizumab Anti-drug Antibody (ADA) Prevalence at Baseline
Description
Spartalizumab ADA prevalence at baseline was calculated as the percentage of participants who had an spartalizumab ADA positive result at baseline.
Time Frame
Baseline
Title
Spartalizumab ADA Incidence
Description
Spartalizumab ADA incidence was calculated as the percentage of participants who were treatment-induced spartalizumab ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted spartalizumab ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
Time Frame
Throughout study until 150 days after the last dose of spartalizumab, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3).
Title
Trough Concentration (Ctrough) for Spartalizumab
Description
Ctrough for spartalizumab refers to the serum concentration of spartalizumab immediately prior to the administration of a dose of spartalizumab on Day 1 of Cycle 2 and later cycles.
Time Frame
Pre-infusion on Day 1 of each Cycle starting from Cycle 2, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days
Title
Pre-dose Plasma Concentration for Dabrafenib
Description
Plasma concentration of dabrafenib immediately prior to the administration of a dose of dabrafenib.
Time Frame
Pre-infusion on Day 1 of every cycle from Cycle 2 to 12, and then every 6 cycles from Cycle 18 to 36, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days
Title
Pre-dose Plasma Concentration for Trametinib
Description
Plasma concentration of trametinib immediately prior to the administration of a dose of trametinib.
Time Frame
Pre-infusion on Day 1 of every cycle from Cycle 2 to 12, and then every 6 cycles from Cycle 18 to 36, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days
Title
Number of Participants With Dose Interruptions
Description
Number of participants with dose interruptions for spartalizumab, dabrafenib and trametinib
Time Frame
From baseline to end of treatment, up to 5 years
Title
Number of Participants With Dose Reductions
Description
Number of patients with dose reductions for spartalizumab, dabrafenib and trametinib
Time Frame
From baseline to end of treatment, up to 5 years
Title
Relative Dose Intensity
Description
Relative dose intensity for spartalizumab, dabrafenib and trametinib computed as the ratio of dose intensity and planned dose intensity
Time Frame
From baseline to end of treatment, up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
California Cancer Associates for Research and Excellence SC-2
City
Encinitas
State/Province
California
ZIP/Postal Code
92024
Country
United States
Facility Name
UC Irvine Medical Center SC
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Stanford Cancer Center SC-2
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Kansas Cancer Center SC
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Johns Hopkins U SC
City
Lutherville
State/Province
Maryland
ZIP/Postal Code
21093
Country
United States
Facility Name
Nebraska Cancer Specialists
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68130
Country
United States
Facility Name
NYU Laura and Isaac Perlmutter Cancer Center SC
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
University of Pittsburgh Medical Center SC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Tennessee Medical Center SC
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
University of TX MD Anderson Cancer Center SC-2
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Utah Cancer Specialists SC 2
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Facility Name
Novartis Investigative Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1125ABD
Country
Argentina
Facility Name
Novartis Investigative Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1426ANZ
Country
Argentina
Facility Name
Novartis Investigative Site
City
Rosario
State/Province
Santa Fe
ZIP/Postal Code
S2000KZE
Country
Argentina
Facility Name
Novartis Investigative Site
City
Buenos Aires
ZIP/Postal Code
C1431FWO
Country
Argentina
Facility Name
Novartis Investigative Site
City
Gateshead
State/Province
New South Wales
ZIP/Postal Code
2290
Country
Australia
Facility Name
Novartis Investigative Site
City
North Sydney
State/Province
New South Wales
ZIP/Postal Code
2060
Country
Australia
Facility Name
Novartis Investigative Site
City
Greenslopes
State/Province
Queensland
ZIP/Postal Code
4120
Country
Australia
Facility Name
Novartis Investigative Site
City
Prahran
State/Province
Victoria
ZIP/Postal Code
3181
Country
Australia
Facility Name
Novartis Investigative Site
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Novartis Investigative Site
City
Innsbruck
State/Province
Tyrol
ZIP/Postal Code
6020
Country
Austria
Facility Name
Novartis Investigative Site
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Novartis Investigative Site
City
Linz
ZIP/Postal Code
4020
Country
Austria
Facility Name
Novartis Investigative Site
City
Salzburg
ZIP/Postal Code
A-5020
Country
Austria
Facility Name
Novartis Investigative Site
City
St Poelten
ZIP/Postal Code
3100
Country
Austria
Facility Name
Novartis Investigative Site
City
Jette
State/Province
Brussel
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Curitiba
State/Province
PR
ZIP/Postal Code
80530 010
Country
Brazil
Facility Name
Novartis Investigative Site
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90035-003
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
01246 000
Country
Brazil
Facility Name
Novartis Investigative Site
City
Rio de Janeiro
ZIP/Postal Code
20560-120
Country
Brazil
Facility Name
Novartis Investigative Site
City
Plovdiv
ZIP/Postal Code
4004
Country
Bulgaria
Facility Name
Novartis Investigative Site
City
Sofia
ZIP/Postal Code
1303
Country
Bulgaria
Facility Name
Novartis Investigative Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Novartis Investigative Site
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
Novartis Investigative Site
City
Temuco
State/Province
Araucania
ZIP/Postal Code
4810469
Country
Chile
Facility Name
Novartis Investigative Site
City
Santiago
ZIP/Postal Code
7500921
Country
Chile
Facility Name
Novartis Investigative Site
City
Santiago
ZIP/Postal Code
8420383
Country
Chile
Facility Name
Novartis Investigative Site
City
Zlin
State/Province
Czech Republic
ZIP/Postal Code
762 75
Country
Czechia
Facility Name
Novartis Investigative Site
City
Hradec Kralove
State/Province
CZE
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Novartis Investigative Site
City
Olomouc
State/Province
CZE
ZIP/Postal Code
779 00
Country
Czechia
Facility Name
Novartis Investigative Site
City
Ostrava
State/Province
Poruba
ZIP/Postal Code
708 52
Country
Czechia
Facility Name
Novartis Investigative Site
City
Brno
ZIP/Postal Code
65653
Country
Czechia
Facility Name
Novartis Investigative Site
City
Praha 10
ZIP/Postal Code
100 34
Country
Czechia
Facility Name
Novartis Investigative Site
City
Praha
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Novartis Investigative Site
City
Aarhus
ZIP/Postal Code
8000 C
Country
Denmark
Facility Name
Novartis Investigative Site
City
Le Mans
State/Province
Cedex 09
ZIP/Postal Code
72037
Country
France
Facility Name
Novartis Investigative Site
City
Limoges
State/Province
Haute Vienne
ZIP/Postal Code
87000
Country
France
Facility Name
Novartis Investigative Site
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
Novartis Investigative Site
City
Besancon Cedex
ZIP/Postal Code
25030
Country
France
Facility Name
Novartis Investigative Site
City
Bobigny Cedex
ZIP/Postal Code
93009
Country
France
Facility Name
Novartis Investigative Site
City
Bordeaux Cedex
ZIP/Postal Code
33075
Country
France
Facility Name
Novartis Investigative Site
City
Boulogne Billancourt
ZIP/Postal Code
92104
Country
France
Facility Name
Novartis Investigative Site
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
Novartis Investigative Site
City
Clermont Ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
Novartis Investigative Site
City
Dijon
ZIP/Postal Code
21000
Country
France
Facility Name
Novartis Investigative Site
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Novartis Investigative Site
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Novartis Investigative Site
City
Lorient
ZIP/Postal Code
56322
Country
France
Facility Name
Novartis Investigative Site
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
Novartis Investigative Site
City
Marseille Cedex 05
ZIP/Postal Code
13885
Country
France
Facility Name
Novartis Investigative Site
City
Mulhouse cedex
ZIP/Postal Code
68070
Country
France
Facility Name
Novartis Investigative Site
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
Novartis Investigative Site
City
Paris 10
ZIP/Postal Code
75475
Country
France
Facility Name
Novartis Investigative Site
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
Novartis Investigative Site
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Novartis Investigative Site
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
Novartis Investigative Site
City
Rouen Cedex
ZIP/Postal Code
76031
Country
France
Facility Name
Novartis Investigative Site
City
Strasbourg Cedex
ZIP/Postal Code
67091
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Novartis Investigative Site
City
Vandoeuvre-les-Nancy
ZIP/Postal Code
54519
Country
France
Facility Name
Novartis Investigative Site
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
Novartis Investigative Site
City
Mannheim
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
68305
Country
Germany
Facility Name
Novartis Investigative Site
City
Regensburg
State/Province
Bavaria
ZIP/Postal Code
93053
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13578
Country
Germany
Facility Name
Novartis Investigative Site
City
Bonn
ZIP/Postal Code
53105
Country
Germany
Facility Name
Novartis Investigative Site
City
Chemnitz
ZIP/Postal Code
09117
Country
Germany
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Novartis Investigative Site
City
Duesseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Novartis Investigative Site
City
Erfurt
ZIP/Postal Code
99089
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Novartis Investigative Site
City
Gera
ZIP/Postal Code
07548
Country
Germany
Facility Name
Novartis Investigative Site
City
Halle Saale
ZIP/Postal Code
06120
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Novartis Investigative Site
City
Homburg
ZIP/Postal Code
66421
Country
Germany
Facility Name
Novartis Investigative Site
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Novartis Investigative Site
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Novartis Investigative Site
City
Marburg
ZIP/Postal Code
35039
Country
Germany
Facility Name
Novartis Investigative Site
City
Minden
ZIP/Postal Code
32429
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenchen
ZIP/Postal Code
81377
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenster
ZIP/Postal Code
48157
Country
Germany
Facility Name
Novartis Investigative Site
City
Stade
ZIP/Postal Code
21682
Country
Germany
Facility Name
Novartis Investigative Site
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
115 27
Country
Greece
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
18547
Country
Greece
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
H 1122
Country
Hungary
Facility Name
Novartis Investigative Site
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Novartis Investigative Site
City
Szeged
ZIP/Postal Code
H 6725
Country
Hungary
Facility Name
Novartis Investigative Site
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Novartis Investigative Site
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Novartis Investigative Site
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Novartis Investigative Site
City
Bari
State/Province
BA
ZIP/Postal Code
70124
Country
Italy
Facility Name
Novartis Investigative Site
City
Bergamo
State/Province
BG
ZIP/Postal Code
24127
Country
Italy
Facility Name
Novartis Investigative Site
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Facility Name
Novartis Investigative Site
City
Brescia
State/Province
BS
ZIP/Postal Code
25123
Country
Italy
Facility Name
Novartis Investigative Site
City
Meldola
State/Province
FC
ZIP/Postal Code
47014
Country
Italy
Facility Name
Novartis Investigative Site
City
Genova
State/Province
GE
ZIP/Postal Code
16132
Country
Italy
Facility Name
Novartis Investigative Site
City
Monza
State/Province
MB
ZIP/Postal Code
20900
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20141
Country
Italy
Facility Name
Novartis Investigative Site
City
Modena
State/Province
MO
ZIP/Postal Code
41124
Country
Italy
Facility Name
Novartis Investigative Site
City
Padova
State/Province
PD
ZIP/Postal Code
35100
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00167
Country
Italy
Facility Name
Novartis Investigative Site
City
Siena
State/Province
SI
ZIP/Postal Code
53100
Country
Italy
Facility Name
Novartis Investigative Site
City
Candiolo
State/Province
TO
ZIP/Postal Code
10060
Country
Italy
Facility Name
Novartis Investigative Site
City
Torino
State/Province
TO
ZIP/Postal Code
10126
Country
Italy
Facility Name
Novartis Investigative Site
City
Verona
State/Province
VR
ZIP/Postal Code
37126
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Kyushu University Hospital
City
Fukuoka city
State/Province
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Kyoto University Hospital
City
Sakyo Ku
State/Province
Kyoto
ZIP/Postal Code
606 8507
Country
Japan
Facility Name
Osaka International Cancer Institute
City
Osaka-city
State/Province
Osaka
ZIP/Postal Code
541-8567
Country
Japan
Facility Name
Tokyo Metropolitan Komagome Hospital
City
Bunkyo ku
State/Province
Tokyo
ZIP/Postal Code
113-8677
Country
Japan
Facility Name
National Cancer Hospital
City
Chuo ku
State/Province
Tokyo
ZIP/Postal Code
104 0045
Country
Japan
Facility Name
Novartis Investigative Site
City
Mexico
State/Province
Distrito Federal
ZIP/Postal Code
14080
Country
Mexico
Facility Name
Novartis Investigative Site
City
Leon
State/Province
Guanajuato
ZIP/Postal Code
37178
Country
Mexico
Facility Name
Novartis Investigative Site
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44100
Country
Mexico
Facility Name
Novartis Investigative Site
City
Breda
ZIP/Postal Code
4819 EV
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Leiden
ZIP/Postal Code
2300 RC
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Oslo
ZIP/Postal Code
0379
Country
Norway
Facility Name
Novartis Investigative Site
City
Gdansk
ZIP/Postal Code
80 952
Country
Poland
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
02 781
Country
Poland
Facility Name
Novartis Investigative Site
City
Lisboa
ZIP/Postal Code
1099 023
Country
Portugal
Facility Name
Novartis Investigative Site
City
Porto
ZIP/Postal Code
4200-072
Country
Portugal
Facility Name
Novartis Investigative Site
City
Chelyabinsk
ZIP/Postal Code
454048
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Moscow
ZIP/Postal Code
143423
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Nizhny Novgorod
ZIP/Postal Code
603137
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Omsk
ZIP/Postal Code
644013
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Saint Petersburg
ZIP/Postal Code
198255
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Samara
ZIP/Postal Code
443011
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
St Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Malaga
State/Province
Andalucia
ZIP/Postal Code
29010
Country
Spain
Facility Name
Novartis Investigative Site
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41009
Country
Spain
Facility Name
Novartis Investigative Site
City
Oviedo
State/Province
Asturias
ZIP/Postal Code
33011
Country
Spain
Facility Name
Novartis Investigative Site
City
Jerez
State/Province
Cadiz
ZIP/Postal Code
11407
Country
Spain
Facility Name
Novartis Investigative Site
City
Badalona
State/Province
Catalunya
ZIP/Postal Code
08916
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46014
Country
Spain
Facility Name
Novartis Investigative Site
City
La Coruna
State/Province
Galicia
ZIP/Postal Code
15006
Country
Spain
Facility Name
Novartis Investigative Site
City
Las Palmas De Gran Canarias
State/Province
Las Palmas De Gran Canaria
ZIP/Postal Code
35016
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Novartis Investigative Site
City
Goteborg
ZIP/Postal Code
SE-413 45
Country
Sweden
Facility Name
Novartis Investigative Site
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
Novartis Investigative Site
City
Stockholm
ZIP/Postal Code
SE 171 76
Country
Sweden
Facility Name
Novartis Investigative Site
City
Aarau
ZIP/Postal Code
5001
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Zuerich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Songkhla
State/Province
Hat Yai
ZIP/Postal Code
90110
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Novartis Investigative Site
City
Truro
State/Province
Cornwall
ZIP/Postal Code
TR1 3LJ
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Surrey
State/Province
England
ZIP/Postal Code
GU2 7XX
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Northwood
State/Province
Middlesex
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Sutton
State/Province
Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Leicester
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Middlesbrough
ZIP/Postal Code
TS4 3BW
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Preston
ZIP/Postal Code
PR2 9HT
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Citations:
PubMed Identifier
35728875
Citation
Tawbi HA, Robert C, Brase JC, Gusenleitner D, Gasal E, Garrett J, Savchenko A, Gorgun G, Flaherty KT, Ribas A, Dummer R, Schadendorf D, Long GV, Nathan PD, Ascierto PA. Spartalizumab or placebo in combination with dabrafenib and trametinib in patients with BRAF V600-mutant melanoma: exploratory biomarker analyses from a randomized phase 3 trial (COMBI-i). J Immunother Cancer. 2022 Jun;10(6):e004226. doi: 10.1136/jitc-2021-004226.
Results Reference
derived
PubMed Identifier
35030011
Citation
Dummer R, Long GV, Robert C, Tawbi HA, Flaherty KT, Ascierto PA, Nathan PD, Rutkowski P, Leonov O, Dutriaux C, Mandala M, Lorigan P, Ferrucci PF, Grob JJ, Meyer N, Gogas H, Stroyakovskiy D, Arance A, Brase JC, Green S, Haas T, Masood A, Gasal E, Ribas A, Schadendorf D. Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600-Mutant Unresectable or Metastatic Melanoma. J Clin Oncol. 2022 May 1;40(13):1428-1438. doi: 10.1200/JCO.21.01601. Epub 2022 Jan 14.
Results Reference
derived
PubMed Identifier
33020648
Citation
Dummer R, Lebbe C, Atkinson V, Mandala M, Nathan PD, Arance A, Richtig E, Yamazaki N, Robert C, Schadendorf D, Tawbi HA, Ascierto PA, Ribas A, Flaherty KT, Pakhle N, Campbell CD, Gusenleitner D, Masood A, Brase JC, Gasal E, Long GV. Combined PD-1, BRAF and MEK inhibition in advanced BRAF-mutant melanoma: safety run-in and biomarker cohorts of COMBI-i. Nat Med. 2020 Oct;26(10):1557-1563. doi: 10.1038/s41591-020-1082-2. Epub 2020 Oct 5.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs