A Phase 3 interventional study of Spartalizumab and Placebo in Melanoma, sponsored by Novartis Pharmaceuticals. Terminated at 179 sites in 29 countries. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2025-09-18.
Sponsored by Novartis Pharmaceuticals · Phase 3, Interventional, and Treatment
The purpose of this study was to evaluate safety and efficacy of the combination of an anti-PD-1 antibody (PDR001), a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) in patients with BRAF V600 mutant, unresectable and metastatic melanoma.
This study was designed as a phase III, multi-center study consisting of 3 parts:
For all parts of the study, the treatment 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 discontinued study treatment without disease progression as per RECIST 1.1 continued 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 entered 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).
3,006 studies on the registry are indexed under Melanoma; 520 are open to participants now.
This study's enrollment of 568 is above the median of 38 across 2,351 interventional studies indexed under Melanoma.
Browse Melanoma studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.
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Inclusion criteria Part 1: Safety run-in
Part 2: Biomarker cohort
Part 3: Double-blind, randomized, placebo-controlled part
Exclusion Criteria:
Part 1: Safety run-in
Parts 2 \& 3: Biomarker cohort \& double-blind, randomized, placebo-controlled part
Other protocol-defined Inclusion/Exclusion may apply.
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).
Biological: Spartalizumab · Drug: Dabrafenib · Drug: Trametinib
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).
Biological: Spartalizumab · Drug: Dabrafenib · Drug: Trametinib
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)
Biological: Spartalizumab · Drug: Dabrafenib · Drug: Trametinib
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)
Other: Placebo · Drug: Dabrafenib · Drug: Trametinib
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
Also known as: PDR001
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
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
Time frame: Up to 8 weeks (Part 1)
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
Time frame: Baseline, Cycle 1 Day 15 and Cycle 3 Day 1 (Part 2). Each cycle is 28 days
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
Time frame: Baseline, Cycle 1 Day 15 and Cycle 3 Day 1 (Part 2). Each cycle is 28 days
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.
Time frame: Up to disease progression or death due to any cause, whichever occurs first, assessed up to 2.8 years (Part 3)
Overall Survival (OS)
Overall survival was 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 7 years
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
Time frame: Part 1: Up to 3.3 years. Part 2: Up to 3 years. Part 3: Up to 2.8 years
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
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)
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.
Time frame: Part 1: Up to 3.3 years. Part 2: Up to 3 years. Part 3: Up to 2.8 year
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.
Time frame: From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
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.
Time frame: From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
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.
Time frame: From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
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.
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)
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.
Time frame: From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
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.
Time frame: From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
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.
Time frame: Up to disease progression or death due to any cause, up to 2.8 years (Part 3)
Randomized (Part 3): OS by PD-L1 Expression
Overall survival was defined as the time from date of randomization to date of death due to any cause. OS analysis was performed by PD-L1 subgroup (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 death due to any cause, assessed up to approximately 7 years
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.
Time frame: 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)
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).
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.
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
Pre-dose Plasma Concentration for Dabrafenib
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
Pre-dose Plasma Concentration for Trametinib
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
Number of Participants With Dose Interruptions
Number of participants with dose interruptions for spartalizumab, dabrafenib and trametinib
Time frame: From baseline to end of treatment, assessed up to approximately 7 years
Number of Participants With Dose Reductions
Number of patients with dose reductions for spartalizumab, dabrafenib and trametinib
Time frame: From baseline to end of treatment, assessed up to approximately 7 years
Relative Dose Intensity
Relative dose intensity for spartalizumab, dabrafenib and trametinib computed as the ratio (expressed as percentage) of dose intensity and planned dose intensity: * Spartalizumab (PDR001) = \[Dose intensity (mg/4W) / planned dose intensity (mg/4W)\]\*100. * Trametinib and Dabrafenib = \[Dose intensity (mg/day) / planned dose intensity (mg/day)\]\*100.
Time frame: From baseline to end of treatment, assessed up to approximately 7 years
Part 1 and 2 were conducted in 18 centers across 12 countries. Part 3 is conducted in 190 centers across 29 countries
| Milestone | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|---|
| Started | 9 | 27 | 267 | 265 |
| Treated | 9 | 27 | 267 | 264 |
| Completed | 0 | 0 | 0 | 0 |
| Not completed | 9 | 27 | 267 | 265 |
| Withdrew: Progressive disease | 3 | 15 | 114 | 151 |
| Withdrew: Subject/guardian decision | 1 | 1 | 14 | 22 |
| Withdrew: Death | 0 | 1 | 13 | 13 |
| Withdrew: Protocol deviation | 1 | 0 | 1 | 1 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 | 0 |
| Withdrew: Physician decision | 0 | 0 | 22 | 13 |
| Withdrew: Adverse event | 2 | 9 | 60 | 28 |
| Withdrew: Study terminated by sponsor | 2 | 1 | 42 | 37 |
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
| Participants | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|
| Safety Run-In (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs) | 1 |
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
| Percentage of positive tumor cells | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|
| Cycle 1 Day 15 | 1.7 ± 13.05 |
| Cycle 3 Day 1 | 2.7 ± 7.63 |
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
| Percentage Marker Area | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|
| Cycle 1 Day 15 | 0.4 ± 3.22 |
| Cycle 3 Day 1 | 1.2 ± 2.43 |
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.
| Months | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|
| Randomized (Part 3): Progression-Free Survival (PFS) as Per Investigator's Assessment by RECIST 1.1 | 16.2 (12.7 to 23.9) | 12.0 (10.2 to 15.4) |
Overall survival was defined as the time from date of randomization to date of death due to any cause
| Months | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|---|
| Overall Survival (OS) | NA (12.2 to NA) | 30.7 (21.3 to 67.4) | 61.5 (41.6 to NA) | 41.6 (30.6 to 56.9) |
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
| Percentage of participants | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|---|
| Overall Response Rate (ORR) as Per Investigator's Assessment by RECIST 1.1 | 100.0 (66.4 to 100.0) | 70.4 (49.8 to 86.2) | 68.5 (62.6 to 74.1) | 64.2 (58.1 to 69.9) |
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
| Months | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|---|
| Duration of Response (DOR) as Per Investigator's Assessment by RECIST 1.1 | NA (8.3 to NA) | 20.0 (9.4 to NA) | NA (18.6 to NA) | 20.7 (13.0 to NA) |
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.
| Percentage of participants | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|---|
| Disease Control Rate (DCR) as Per Investigator's Assessment by RECIST 1.1 | 100.0 (66.4 to 100.0) | 92.6 (75.7 to 99.1) | 84.3 (79.3 to 88.4) | 86.4 (81.7 to 90.3) |
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.
| Score on a Scale | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|
| Cycle 4 Day 1 | 0.81 ± 19.300 | 2.20 ± 24.918 |
| Cycle 6 Day 1 | 1.22 ± 25.050 | 1.90 ± 21.197 |
| Cycle 8 Day 1 | 0.00 ± 24.526 | 0.50 ± 19.608 |
| Cycle 10 Day 1 | 1.88 ± 23.088 | 0.27 ± 18.752 |
| Cycle 12 Day 1 | 0.61 ± 25.906 | 0.00 ± 24.541 |
| Cycle 14 Day 1 | 0.65 ± 23.561 | -0.89 ± 23.306 |
| Cycle 16 Day 1 | 0.82 ± 25.186 | 1.76 ± 24.142 |
| Cycle 18 Day 1 | -0.46 ± 24.106 | -0.10 ± 19.193 |
| Cycle 20 Day 1 | 1.93 ± 21.766 | -1.02 ± 23.144 |
| Cycle 22 Day 1 | 0.95 ± 22.047 | 2.29 ± 21.947 |
| Cycle 25 Day 1 | 3.57 ± 23.981 | -0.24 ± 25.497 |
| Cycle 28 Day 1 | 4.50 ± 19.793 | 1.06 ± 22.513 |
| Cycle 31 Day 1 | 11.59 ± 24.967 | 6.73 ± 21.084 |
| Cycle 34 Day 1 | 16.67 ± 47.140 | 13.89 ± 20.184 |
| 30 days post-progression | -11.59 ± 24.967 | -7.78 ± 29.274 |
| 60 days post-progression | -11.54 ± 16.506 | -17.19 ± 24.050 |
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.
| Score on a Scale | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|
| Cycle 4 Day 1 | -1.52 ± 16.243 | -0.70 ± 17.618 |
| Cycle 6 Day 1 | -2.38 ± 16.121 | -0.60 ± 14.824 |
| Cycle 8 Day 1 | -1.29 ± 18.350 | -0.59 ± 15.687 |
| Cycle 10 Day 1 | -0.18 ± 17.985 | -1.11 ± 13.736 |
| Cycle 12 Day 1 | -1.39 ± 18.108 | -0.85 ± 10.652 |
| Cycle 14 Day 1 | -2.42 ± 16.720 | -2.61 ± 12.320 |
| Cycle 16 Day 1 | -4.19 ± 20.301 | -2.24 ± 13.331 |
| Cycle 18 Day 1 | -3.48 ± 18.862 | -3.55 ± 13.474 |
| Cycle 20 Day 1 | -4.07 ± 15.316 | -1.73 ± 11.536 |
| Cycle 22 Day 1 | -3.21 ± 15.538 | -0.85 ± 11.157 |
| Cycle 25 Day 1 | -1.35 ± 16.510 | -2.67 ± 13.158 |
| Cycle 28 Day 1 | -0.80 ± 13.843 | -2.67 ± 15.953 |
| Cycle 31 Day 1 | -2.03 ± 10.719 | -1.79 ± 9.533 |
| Cycle 34 Day 1 | 0.00 ± 0.000 | -3.33 ± 5.578 |
| 30 days post-progression | -6.67 ± 18.641 | -8.67 ± 19.973 |
| 60 days post-progression | -13.85 ± 15.977 | -21.25 ± 27.991 |
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.
| Score on a Scale | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|
| Cycle 4 Day 1 | -5.24 ± 26.434 | -5.29 ± 24.881 |
| Cycle 6 Day 1 | -6.43 ± 28.820 | -7.49 ± 23.611 |
| Cycle 8 Day 1 | -4.91 ± 29.176 | -4.11 ± 24.420 |
| Cycle 10 Day 1 | -7.95 ± 28.346 | -4.76 ± 23.557 |
| Cycle 12 Day 1 | -8.33 ± 28.890 | -5.26 ± 22.646 |
| Cycle 14 Day 1 | -5.50 ± 28.140 | -3.56 ± 23.062 |
| Cycle 16 Day 1 | -5.86 ± 26.220 | -4.44 ± 25.820 |
| Cycle 18 Day 1 | -3.15 ± 30.178 | -3.21 ± 20.898 |
| Cycle 20 Day 1 | -4.47 ± 30.659 | -2.85 ± 23.249 |
| Cycle 22 Day 1 | -5.49 ± 27.049 | -3.54 ± 23.969 |
| Cycle 25 Day 1 | -6.25 ± 28.868 | -4.76 ± 20.685 |
| Cycle 28 Day 1 | -3.00 ± 26.872 | -3.03 ± 22.701 |
| Cycle 31 Day 1 | -10.14 ± 24.995 | -7.05 ± 34.696 |
| Cycle 34 Day 1 | -8.33 ± 11.785 | -5.56 ± 8.607 |
| 30 days post-progression | 9.42 ± 28.791 | 0.56 ± 28.190 |
| 60 days post-progression | 15.38 ± 19.792 | 11.46 ± 24.884 |
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.
| Months | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|
| 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 | 19.4 (15.7 to 24.9) | 22.1 (17.5 to NA) |
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.
| Score on a scale | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|
| Cycle 4 Day 1 | 0.83 ± 6.600 | 0.87 ± 6.185 |
| Cycle 6 Day 1 | 1.01 ± 7.370 | 1.18 ± 6.219 |
| Cycle 8 Day 1 | 1.14 ± 7.284 | 1.09 ± 5.742 |
| Cycle 10 Day 1 | 1.52 ± 7.314 | 0.54 ± 6.492 |
| Cycle 12 Day 1 | 1.21 ± 7.515 | 0.47 ± 5.974 |
| Cycle 14 Day 1 | 0.77 ± 7.071 | 0.65 ± 6.681 |
| Cycle 16 Day 1 | 0.93 ± 6.451 | 0.71 ± 6.374 |
| Cycle 18 Day 1 | 1.23 ± 7.095 | 0.47 ± 6.152 |
| Cycle 20 Day 1 | 1.28 ± 6.634 | 0.53 ± 5.875 |
| Cycle 22 Day 1 | 1.87 ± 6.215 | 0.79 ± 5.970 |
| Cycle 25 Day 1 | 2.73 ± 5.950 | 0.74 ± 6.792 |
| Cycle 28 Day 1 | 2.46 ± 5.195 | 0.61 ± 8.020 |
| Cycle 31 Day 1 | 3.29 ± 5.702 | 1.88 ± 6.154 |
| Cycle 34 Day 1 | -0.50 ± 2.121 | 4.60 ± 3.578 |
| 30 days post-progression | 0.33 ± 7.620 | -1.07 ± 8.590 |
| 60 days post-progression | -2.60 ± 5.734 | -3.06 ± 8.948 |
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.
| Score on a Scale | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|
| Cycle 4 Day 1 | 1.85 ± 16.567 | 2.16 ± 19.733 |
| Cycle 6 Day 1 | 1.55 ± 20.751 | 3.10 ± 16.095 |
| Cycle 8 Day 1 | 0.39 ± 20.246 | 2.60 ± 15.200 |
| Cycle 10 Day 1 | 2.45 ± 19.050 | 2.52 ± 16.144 |
| Cycle 12 Day 1 | 1.88 ± 24.653 | 1.42 ± 15.695 |
| Cycle 14 Day 1 | 2.62 ± 19.455 | 1.71 ± 14.337 |
| Cycle 16 Day 1 | 1.30 ± 18.640 | 2.79 ± 16.996 |
| Cycle 18 Day 1 | 2.16 ± 20.762 | 1.91 ± 16.743 |
| Cycle 20 Day 1 | 1.34 ± 17.831 | 1.28 ± 16.108 |
| Cycle 22 Day 1 | 3.01 ± 19.102 | 1.55 ± 14.973 |
| Cycle 25 Day 1 | 4.47 ± 19.489 | 0.26 ± 14.784 |
| Cycle 28 Day 1 | 4.20 ± 17.545 | -0.39 ± 18.529 |
| Cycle 31 Day 1 | 6.45 ± 19.561 | -0.08 ± 16.747 |
| Cycle 34 Day 1 | -9.50 ± 14.849 | 5.60 ± 19.008 |
| 30 days post-progression | -4.04 ± 22.033 | -10.24 ± 23.532 |
| 60 days post-progression | -19.25 ± 19.923 | -8.19 ± 21.192 |
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.
| Months | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|
| PD-L1 negative (<1%) | 12.0 (10.1 to 15.7) | 10.3 (7.5 to 13.0) |
| PD-L1 positive (>=1%) | 26.6 (17.4 to NA) | 15.4 (10.2 to 25.3) |
Overall survival was defined as the time from date of randomization to date of death due to any cause. OS analysis was performed by PD-L1 subgroup (positive, negative) where a positive status was defined as having ≥ 1% expression and a negative status was defined as having \< 1% expression.
| Months | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|
| PD-L1 negative (<1%) | 41.6 (27.6 to NA) | 21.0 (16.9 to 33.4) |
| PD-L1 positive (>=1%) | NA (45.4 to NA) | 61.3 (41.2 to NA) |
Spartalizumab ADA prevalence at baseline was calculated as the percentage of participants who had an spartalizumab ADA positive result at baseline.
| Participants | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|
| Spartalizumab Anti-drug Antibody (ADA) Prevalence at Baseline | 0 | 0 | 4 |
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)
| Participants | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|
| Spartalizumab ADA Incidence | 0 | 5 | 55 |
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.
| microgram (μg)/miliLiter (mL) | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|
| Cycle 2 | 31.9 ± 4.59 | 31.5 ± 20.3 | 28.4 ± 13.4 |
| Cycle 3 | 41.1 ± 7.07 | 56.1 ± 34.2 | 43.5 ± 19.1 |
| Cycle 4 | 47.8 | 46.9 ± 18.8 | 50.5 ± 24.2 |
| Cycle 5 | 46.3 | 56.7 ± 19.5 | 56.4 ± 24.5 |
| Cycle 6 | 53.8 ± 16.9 | 60.9 ± 23.6 | 58.8 ± 26.5 |
| Cycle 7 | 56.1 ± 12.1 | 62.2 ± 33.3 | 63.7 ± 29.6 |
| Cycle 8 | 57.9 ± 12.7 | 65.8 ± 32.8 | 64.1 ± 29.9 |
| Cycle 9 | 60.2 ± 30.9 | 69.5 ± 25.2 | 67.8 ± 33.5 |
| Cycle 10 | 62.1 ± 22.5 | 68.4 ± 33.2 | 63.8 ± 28.4 |
| Cycle 11 | 66.9 ± 15.8 | 63.2 ± 35.8 | 62.1 ± 27.9 |
| Cycle 12 | 67.0 ± 16.5 | 61.6 ± 29.3 | 60.7 ± 27.2 |
Plasma concentration of dabrafenib immediately prior to the administration of a dose of dabrafenib.
| nanogram (ng)/ miliLiter (mL) | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|---|
| Cycle 2 | 33.7 ± 27.4 | 149 ± 391 | 208 ± 473 | 234 ± 475 |
| Cycle 3 | 25.5 ± 10.4 | 183 ± 469 | 192 ± 607 | 135 ± 266 |
| Cycle 4 | 23.0 ± 15.8 | 372 ± 811 | 169 ± 404 | 167 ± 328 |
| Cycle 5 | 28.8 ± 30.6 | 152 ± 293 | 130 ± 317 | 152 ± 363 |
| Cycle 6 | 15.1 ± 16.3 | 73.7 ± 131 | 198 ± 521 | 94.6 ± 186 |
| Cycle 7 | 20.9 ± 13.9 | 40.0 ± 20.0 | 180 ± 510 | 121 ± 279 |
| Cycle 8 | 22.9 ± 16.8 | 28.0 ± 10.4 | 173 ± 532 | 97.2 ± 177 |
| Cycle 9 | 22.3 ± 7.59 | 43.3 ± 40.6 | 143 ± 394 | 133 ± 259 |
| Cycle 10 | 24.5 ± 9.19 | 60.0 ± 28.3 | 167 ± 472 | 122 ± 266 |
| Cycle 11 | 154 ± 250 | 33.8 ± 22.6 | 174 ± 667 | 119 ± 238 |
| Cycle 12 | 10.9 ± 10.3 | 41.3 ± 37.2 | 148 ± 396 | 146 ± 295 |
| Cycle 18 | 19.0 | 50.6 ± 49.7 | 180 ± 618 | 167 ± 385 |
| Cycle 24 | — | 91.5 ± 98.3 | 147 ± 344 | 60.2 ± 67.9 |
| Cycle 30 | 40.2 | — | 226 ± 488 | 47.6 ± 23.2 |
| Cycle 36 | 47.6 | — | — | — |
Plasma concentration of trametinib immediately prior to the administration of a dose of trametinib.
| ng/mL | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|---|
| Cycle 2 | 11.7 ± 4.09 | 11.2 ± 3.4 | 11.5 ± 4.73 | 13.9 ± 9.36 |
| Cycle 3 | 8.34 ± 0.354 | 12.2 ± 2.55 | 11.4 ± 5.98 | 12.3 ± 5.59 |
| Cycle 4 | 10.7 ± 1.64 | 12.5 ± 4.84 | 11.7 ± 4.62 | 11.9 ± 5.04 |
| Cycle 5 | 10.1 | 12.6 ± 5.03 | 11.3 ± 4.91 | 11.6 ± 4.49 |
| Cycle 6 | 10.0 ± 1.38 | 11.8 ± 3.73 | 11.6 ± 5.12 | 10.9 ± 3.52 |
| Cycle 7 | 11.6 ± 3.8 | 11.8 ± 5.24 | 12.0 ± 4.86 | 11.0 ± 4.26 |
| Cycle 8 | 9.24 ± 3.06 | 10.2 ± 4.13 | 10.3 ± 3.92 | 11.3 ± 4.08 |
| Cycle 9 | 8.73 ± 3.35 | 10.5 ± 4.43 | 10.9 ± 4.57 | 11.6 ± 4.22 |
| Cycle 10 | 8.24 | 10.5 ± 4.02 | 10.9 ± 4.47 | 11.8 ± 4.26 |
| Cycle 11 | 10.7 | 11.6 ± 4.69 | 10.3 ± 3.67 | 11.4 ± 3.57 |
| Cycle 12 | 10.6 ± 3.92 | 11.0 ± 4.53 | 10.6 ± 4.31 | 11.2 ± 3.82 |
| Cycle 18 | 10.1 | 13.0 ± 4.6 | 9.66 ± 3.49 | 12.1 ± 5.13 |
| Cycle 24 | — | 13.4 ± 8.03 | 10.7 ± 4.89 | 10.7 ± 2.21 |
| Cycle 30 | 10.8 | — | 9.34 ± 7.56 | 10.1 ± 2.76 |
| Cycle 36 | 8.97 | — | — | — |
Number of participants with dose interruptions for spartalizumab, dabrafenib and trametinib
| Participants | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|---|
| Spartalizumab (PDR001) — With no dose interruption | 4 | 11 | 120 | 170 |
| Spartalizumab (PDR001) — With at least one dose interruption | 5 | 16 | 147 | 94 |
| Dabrafenib — With no dose interruption | 0 | 2 | 29 | 74 |
| Dabrafenib — With at least one dose interruption | 9 | 25 | 238 | 190 |
| Trametinib — With no dose interruption | 0 | 1 | 29 | 64 |
| Trametinib — With at least one dose interruption | 9 | 26 | 238 | 200 |
Number of patients with dose reductions for spartalizumab, dabrafenib and trametinib
| Participants | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|---|
| Dabrafenib — With neither dose reduction nor interruption | 0 | 2 | 25 | 68 |
| Dabrafenib — With at least one dose reduction and/or interruption | 9 | 25 | 242 | 196 |
| Trametinib — With neither dose reduction nor interruption | 0 | 1 | 28 | 63 |
| Trametinib — With at least one dose reduction and/or interruption | 9 | 26 | 239 | 201 |
Relative dose intensity for spartalizumab, dabrafenib and trametinib computed as the ratio (expressed as percentage) of dose intensity and planned dose intensity: * Spartalizumab (PDR001) = \[Dose intensity (mg/4W) / planned dose intensity (mg/4W)\]\*100. * Trametinib and Dabrafenib = \[Dose intensity (mg/day) / planned dose intensity (mg/day)\]\*100.
| Percentage of planned dose intensity | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD |
|---|---|---|---|---|
| Spartalizumab (PDR001) | 90.7 ± 16.83 | 91.7 ± 10.41 | 94.4 ± 9.21 | 97.5 ± 5.33 |
| Dabrafenib | 62.2 ± 26.36 | 71.3 ± 21.13 | 78.1 ± 21.21 | 89.6 ± 15.10 |
| Trametinib | 65.9 ± 16.90 | 76.2 ± 17.19 | 79.8 ± 19.58 | 89.5 ± 14.86 |
Collected over Adverse Events (AEs) were collected from first dose of study medication until the last dose plus 30 days safety follow-up, assessed up to approximately 86 months. Deaths were recorded from study start date until end of extended follow-up phase (end of study), assessed up to approximately 90 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | 2/9 (22.2%) | 7/9 (77.8%) | 9/9 (100%) |
| Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | 3/27 (11.1%) | 18/27 (66.7%) | 27/27 (100%) |
| Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | 28/267 (10.5%) | 150/267 (56.2%) | 262/267 (98.1%) |
| Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | 33/265 (12.5%) | 123/264 (46.6%) | 250/264 (94.7%) |
| Part 1- Safety run-in: PDR001 400 mg Q4W+Dabrafenib 150 mg BID+Trametinib 2 mg QD (Extended F/Up) | 1/7 (14.3%) | — | — |
| Part 2- Biomarker Cohort: PDR001 400 mg Q4W+Dabrafenib 150 mg BID+Trametinib 2 mg QD(Extended F/Up) | 15/24 (62.5%) | — | — |
| Part 3- Arm 1: PDR001 400 mg Q4W+Dabrafenib 150 mg BID+Trametinib 2 mg QD (Extended F/Up) | 99/239 (41.4%) | — | — |
| Part 3- Arm 2: Placebo+Dabrafenib 150 mg BID+Trametinib 2 mg QD (Extended F/Up) | 117/232 (50.4%) | — | — |
| Event | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 1- Safety run-in: PDR001 400 mg Q4W+Dabrafenib 150 mg BID+Trametinib 2 mg QD (Extended F/Up) | Part 2- Biomarker Cohort: PDR001 400 mg Q4W+Dabrafenib 150 mg BID+Trametinib 2 mg QD(Extended F/Up) | Part 3- Arm 1: PDR001 400 mg Q4W+Dabrafenib 150 mg BID+Trametinib 2 mg QD (Extended F/Up) | Part 3- Arm 2: Placebo+Dabrafenib 150 mg BID+Trametinib 2 mg QD (Extended F/Up) |
|---|---|---|---|---|---|---|---|---|
| PyrexiaGeneral disorders | 4/9 | 4/27 | 46/267 | 16/264 | — | — | — | — |
| HypophysitisEndocrine disorders | 1/9 | 0/27 | 1/267 | 0/264 | — | — | — | — |
| DiarrhoeaGastrointestinal disorders | 1/9 | 0/27 | 3/267 | 2/264 | — | — | — | — |
| Umbilical herniaGastrointestinal disorders | 1/9 | 0/27 | 0/267 | 0/264 | — | — | — | — |
| CholelithiasisHepatobiliary disorders | 1/9 | 0/27 | 1/267 | 0/264 | — | — | — | — |
| HepatitisHepatobiliary disorders | 1/9 | 0/27 | 0/267 | 0/264 | — | — | — | — |
| HypertransaminasaemiaHepatobiliary disorders | 1/9 | 0/27 | 1/267 | 0/264 | — | — | — | — |
| CellulitisInfections and infestations | 1/9 | 1/27 | 5/267 | 1/264 | — | — | — | — |
| PneumoniaInfections and infestations | 1/9 | 1/27 | 5/267 | 3/264 | — | — | — | — |
| Hip fractureInjury, poisoning and procedural complications | 1/9 | 0/27 | 1/267 | 0/264 | — | — | — | — |
| Event | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 1- Safety run-in: PDR001 400 mg Q4W+Dabrafenib 150 mg BID+Trametinib 2 mg QD (Extended F/Up) | Part 2- Biomarker Cohort: PDR001 400 mg Q4W+Dabrafenib 150 mg BID+Trametinib 2 mg QD(Extended F/Up) | Part 3- Arm 1: PDR001 400 mg Q4W+Dabrafenib 150 mg BID+Trametinib 2 mg QD (Extended F/Up) | Part 3- Arm 2: Placebo+Dabrafenib 150 mg BID+Trametinib 2 mg QD (Extended F/Up) |
|---|---|---|---|---|---|---|---|---|
| PyrexiaGeneral disorders | 9/9 | 23/27 | 189/267 | 145/264 | — | — | — | — |
| ChillsGeneral disorders | 8/9 | 9/27 | 86/267 | 63/264 | — | — | — | — |
| FatigueGeneral disorders | 7/9 | 11/27 | 71/267 | 69/264 | — | — | — | — |
| ArthralgiaMusculoskeletal and connective tissue disorders | 6/9 | 15/27 | 87/267 | 80/264 | — | — | — | — |
| CoughRespiratory, thoracic and mediastinal disorders | 6/9 | 12/27 | 63/267 | 49/264 | — | — | — | — |
| Lipase increasedInvestigations | 5/9 | 5/27 | 66/267 | 38/264 | — | — | — | — |
| HeadacheNervous system disorders | 5/9 | 8/27 | 80/267 | 74/264 | — | — | — | — |
| RashSkin and subcutaneous tissue disorders | 4/9 | 13/27 | 76/267 | 68/264 | — | — | — | — |
| AnaemiaBlood and lymphatic system disorders | 4/9 | 10/27 | 49/267 | 31/264 | — | — | — | — |
| NeutropeniaBlood and lymphatic system disorders | 4/9 | 3/27 | 44/267 | 37/264 | — | — | — | — |
| Age, Categorical(Participants) | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 7 | 18 | 189 | 195 | 409 |
| >=65 years | 2 | 9 | 78 | 70 | 159 |
| Sex: Female, Male(Participants) | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Total |
|---|---|---|---|---|---|
| Female | 2 | 12 | 119 | 106 | 239 |
| Male | 7 | 15 | 148 | 159 | 329 |
| Race/Ethnicity, Customized(Participants) | Part 1- Safety run-in: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 2- Biomarker Cohort: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 1: PDR001 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD | Total |
|---|---|---|---|---|---|
| White | 9 | 24 | 225 | 227 | 485 |
| Asian | 0 | 2 | 5 | 5 | 12 |
| Other | 0 | 1 | 15 | 14 | 30 |
| Unknown | 0 | 0 | 22 | 19 | 41 |
Showing the first 100 of 179 sites across 29 countries.
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Plan to share: Yes — 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
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