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Safety and Efficacy Study of PDR001 in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02605967
Recruitment Status : Completed
First Posted : November 17, 2015
Results First Posted : August 12, 2021
Last Update Posted : February 10, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Nasopharyngeal Carcinoma
Interventions Drug: Spartalizumab
Drug: Investigator choice of chemotherapy
Enrollment 122
Recruitment Details Participants took part in 19 investigative sites in 7 countries.
Pre-assignment Details The screening period began once patients had signed the study informed consent. All screening evaluations were performed as closely as possible to the beginning of treatment and never more than 4 weeks before the beginning of the study treatment. After screening, the treatment period started on Cycle 1 Day 1.
Arm/Group Title Spartalizumab 400 mg Q4W Chemotherapy
Hide Arm/Group Description anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab Commonly used chemotherapy as per investigator's choice
Period Title: Overall Study
Started [1] 82 40
Safety Set [2] 82 39
Crossover to Spartalizumab [3] 0 27
Completed 0 0
Not Completed 82 40
Reason Not Completed
subject / guardian decision             1             2
Physician Decision             10             1
Death             4             2
Adverse Event             1             0
progressive disease             66             35
[1]
All participants to whom study treatment was assigned by randomization
[2]
All participants who received at least one dose of study medication and had at least one valid post-screening/post-baseline safety assessment.
[3]
Participants in Chemotherapy arm were allowed to crossover to spartalizumab treatment if they had radiological progression as per RECIST v1.1 by independent central review.
Arm/Group Title Spartalizumab 400 mg Q4W Chemotherapy Total
Hide Arm/Group Description anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab Commonly used chemotherapy as per investigator's choice Total of all reporting groups
Overall Number of Baseline Participants 82 40 122
Hide Baseline Analysis Population Description
There were 122 participants in this trial. Of the 40 subjects from the chemotherapy arm, 25 subjects crossed over to receive spartalizumab.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 82 participants 40 participants 122 participants
51.1  (11.54) 50.5  (12.32) 50.9  (11.75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants 40 participants 122 participants
Female
14
  17.1%
7
  17.5%
21
  17.2%
Male
68
  82.9%
33
  82.5%
101
  82.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants 40 participants 122 participants
Caucasian
12
  14.6%
2
   5.0%
14
  11.5%
Black
0
   0.0%
1
   2.5%
1
   0.8%
Asian
70
  85.4%
37
  92.5%
107
  87.7%
1.Primary Outcome
Title Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment - Number of Participants With Progression or Death
Hide Description

PFS is the time from the date of randomization to the date of event defined as the first documented confirmed progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.

Tumor response was based on central review of tumor scan and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive disease is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. Number of participants in each category (progression, death, censored) is reported in this record.

Time Frame From randomization up to maximum 3.3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W Chemotherapy
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Commonly used chemotherapy as per investigator's choice
Overall Number of Participants Analyzed 82 40
Measure Type: Count of Participants
Unit of Measure: Participants
number of progression
62
  75.6%
32
  80.0%
number of deaths
3
   3.7%
1
   2.5%
number of censored
17
  20.7%
7
  17.5%
2.Primary Outcome
Title Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment - Median PFS
Hide Description

PFS is the time from the date of randomization to the date of event defined as the first documented confirmed progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.

Tumor response was based on central review of tumor scan and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive disease is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.

Time Frame From randomization up to maximum 3.3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W Chemotherapy
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Commonly used chemotherapy as per investigator's choice
Overall Number of Participants Analyzed 82 40
Median (95% Confidence Interval)
Unit of Measure: months
1.9
(1.8 to 2.9)
5.6
(3.7 to 9.2)
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient is not known to have died, survival is censored at the date of last known date the patient was alive.
Time Frame From randomization up to maximum 4.8 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W Chemotherapy
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Commonly used chemotherapy as per investigator's choice
Overall Number of Participants Analyzed 82 40
Median (95% Confidence Interval)
Unit of Measure: months
20.1
(13.6 to 25.5)
16.0
(8.8 to 22.5)
4.Secondary Outcome
Title Overall Response Rate (ORR) as Per RECIST v 1.1
Hide Description

ORR is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). Tumor response was based on central review of overall lesion response according to RECIST 1.1.

For RECIST v1.1, 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 From randomization up to maximum 3.3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W Chemotherapy
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Commonly used chemotherapy as per investigator's choice
Overall Number of Participants Analyzed 82 40
Measure Type: Count of Participants
Unit of Measure: Participants
15
  18.3%
13
  32.5%
5.Secondary Outcome
Title Duration of Response (DOR) as Per RECIST v 1.1
Hide Description DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR) based on central review of overall lesion response according to RECIST 1.1. DOR is defined as the time between the date of first documented response (confirmed CR or confirmed PR) and the date of first documented disease progression or death due to underlying cancer. If a patient not had an event, duration was censored at the date of last adequate tumor assessment.
Time Frame From randomization up to maximum 3.3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants for whom best overall response is complete response (CR) or partial response (PR) as per RECIST 1.1 based on central review.
Arm/Group Title Spartalizumab 400 mg Q4W Chemotherapy
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Commonly used chemotherapy as per investigator's choice
Overall Number of Participants Analyzed 15 13
Median (95% Confidence Interval)
Unit of Measure: months
10.2 [1] 
(7.4 to NA)
5.7
(3.7 to 7.4)
[1]
Not estimable due to insufficient number of participants with events.
6.Secondary Outcome
Title Time to Progression (TTP) as Per RECIST v 1.1
Hide Description

TTP is defined as time from date of randomization to the date of event defined as the first documented progression or death due to underlying cancer. If a subject did not had an event, TTP was censored at the date of last adequate tumor assessment.

Tumor response was based on central review of tumor scan and the assessment criteria was RECIST v1.1. Progressive disease is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.

Time Frame From randomization up to maximum 3.3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W Chemotherapy
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Commonly used chemotherapy as per investigator's choice
Overall Number of Participants Analyzed 82 40
Median (95% Confidence Interval)
Unit of Measure: months
1.9
(1.8 to 2.9)
5.6
(3.7 to 9.3)
7.Secondary Outcome
Title Immune-related Progression-free Survival (irPFS) as Per irRC
Hide Description

irPFS is the time from the date of randomization to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.

Tumor response was based on central review of tumor scan and the assessment criteria was immune-related Response Criteria (irRC). Immune-related progressive disease is at least a 20% increase in the sum of diameters of all measured target lesions including new measurable lesions.

Time Frame From randomization up to maximum 3.3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization to spartalizumab. For the chemotherapy arm, tumor scans for efficacy assessment as per irRC were not planned.
Arm/Group Title Spartalizumab 400 mg Q4W Chemotherapy
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Commonly used chemotherapy as per investigator's choice
Overall Number of Participants Analyzed 82 0
Median (95% Confidence Interval)
Unit of Measure: months
1.9
(1.8 to 3.6)
8.Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) of Spartalizumab
Hide Description Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
Time Frame pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had at least one dose of spartalizumab and had at least one evaluable concentration measurement of spartalizumab. PK samples were only collected in participants to whom spartalizumab was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 82
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ug/mL
Cycle 1 Number Analyzed 78 participants
116
(21.9%)
Cycle 3 Number Analyzed 47 participants
149
(25.8%)
9.Secondary Outcome
Title Time to Reach Maximum Serum Concentration (Tmax) of Spartalizumab
Hide Description Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
Time Frame pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had at least one dose of spartalizumab and had at least one evaluable concentration measurement of spartalizumab. PK samples were only collected in participants to whom spartalizumab was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 82
Median (Full Range)
Unit of Measure: hours
Cycle 1 Number Analyzed 78 participants
1.57
(0.58 to 3.17)
Cycle 3 Number Analyzed 47 participants
1.57
(1.00 to 14.9)
10.Secondary Outcome
Title Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) of Spartalizumab
Hide Description Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation. The duration of the dosing interval (tau) was 28 days.
Time Frame pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had at least one dose of spartalizumab and had at least one evaluable concentration measurement of spartalizumab. PK samples were only collected in participants to whom spartalizumab was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 82
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: day*ug/mL
Cycle 1 Number Analyzed 73 participants
1340
(25.8%)
Cycle 3 Number Analyzed 39 participants
2260
(30.6%)
11.Secondary Outcome
Title Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) of Spartalizumab
Hide Description Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation. The extrapolation of AUC to infinity could be calculated if the percentage of area extrapolated was less than 20% and the regression analysis of the terminal serum elimination phase met a pre-defined criteria of goodness of fit.
Time Frame pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had at least one dose of spartalizumab and the extrapolation of AUC to infinity could be calculated as described in the description of the endpoint. PK samples were only collected in participants to whom spartalizumab was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: day*ug/mL
Cycle 1 Number Analyzed 6 participants
1180
(23.9%)
Cycle 3 Number Analyzed 2 participants
1090
(84.8%)
12.Secondary Outcome
Title Accumulation Ratio (Racc) of Spartalizumab
Hide Description Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Racc was calculated as the ratio between AUCtau Cycle 3 and AUCtau Cycle 1.
Time Frame pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had at least one dose of spartalizumab and had at least one evaluable concentration measurement of spartalizumab. PK samples were only collected in participants to whom spartalizumab was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 39
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
1.61
(19.6%)
13.Secondary Outcome
Title Terminal Elimination Half-life (T1/2) of Spartalizumab
Hide Description Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant.
Time Frame pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had at least one dose of spartalizumab and had at least one evaluable concentration measurement of spartalizumab. PK samples were only collected in participants to whom spartalizumab was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 82
Median (Full Range)
Unit of Measure: days
Cycle 1 Number Analyzed 79 participants
20.1
(7.35 to 41.5)
Cycle 3 Number Analyzed 48 participants
22.7
(5.29 to 48.9)
14.Secondary Outcome
Title Number of Participants With Anti-spartalizumab Antibodies
Hide Description Validated immunoassays were used for screening and confirmation of the presence of anti-spartalizumab antibodies (ADA, anti-drug antibodies) in serum. Number of participants with each ADA status is reported in this record.
Time Frame Baseline (pre-dose on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 655 days).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had at least one dose of spartalizumab and had a determinant baseline immunogenicity (IG) sample and at least one determinant post-baseline IG sample. A determinant IG sample is neither ADA-inconclusive nor unevaluable. IG samples were only collected in participants to whom spartalizumab was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 72
Measure Type: Count of Participants
Unit of Measure: Participants
ADA-negative at baseline
66
  91.7%
ADA-positive at baseline
6
   8.3%
ADA-negative at post-baseline
59
  81.9%
ADA-positive at post-baseline (i.e. ADA incidence)
9
  12.5%
15.Secondary Outcome
Title PD-L1 Percent Positive Tumor
Hide Description The expression of programmed cell death-ligand 1 (PD-L1) was measured in tumor samples by immunohistochemical methods. This record summarizes the PD-L1 positivity percentage in tumor samples.
Time Frame Baseline (screening), Cycle 3 Day 1. The duration of one cycle was 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization to spartalizumab and had a valid assessment for the outcome measure. Biomarker samples were not collected in participants randomized to chemotherapy.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 78
Overall Number of Units Analyzed
Type of Units Analyzed: Tumor samples
79
Median (Full Range)
Unit of Measure: PD-L1 positivity percentage
Baseline Number Analyzed 78 tumor samples
20.00
(0 to 100)
Cycle 3 Day 1 Number Analyzed 1 tumor samples [1] 
90.00
(90.00 to 90.00)
[1]
1 participants
16.Secondary Outcome
Title Percent Marker Area for CD8 Expression in Tumor Samples
Hide Description The expression of CD8 was measured in tumor samples by immunohistochemical methods. This record summarizes the percent marker area for CD8 expression in tumor samples.
Time Frame Baseline (screening), Cycle 3 Day 1. The duration of one cycle was 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization to spartalizumab and had a valid assessment for the outcome measure. Biomarker samples were not collected in participants randomized to chemotherapy.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 78
Overall Number of Units Analyzed
Type of Units Analyzed: Tumor samples
79
Median (Full Range)
Unit of Measure: CD8 percent marker area
Baseline Number Analyzed 78 tumor samples
4.23
(0.1 to 31.8)
Cycle 3 Day 1 Number Analyzed 1 tumor samples [1] 
2.22
(2.22 to 2.22)
[1]
1 participants
17.Secondary Outcome
Title TIL Count in Tumor Samples
Hide Description The count of tumor-infiltrating lymphocytes (TILs) was measured in baseline (screening) and post-baseline paired tumor samples by immunohistochemical methods. This record summarizes the TIL count in tumor samples.
Time Frame Baseline (screening), Cycle 3 Day 1. The duration of one cycle was 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization to spartalizumab and had paired tumor biopsies. Biomarker samples were not collected in participants randomized to chemotherapy.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: TILs
Baseline 10
Cycle 3 Day 1 15
18.Secondary Outcome
Title Fold Change From Baseline in IFN-gamma Levels in Plasma
Hide Description The levels of interferon-gamma (IFN-gamma) were measured in plasma samples by immunoassay methods. This record summarizes the fold change from baseline in IFN-gamma levels in plasma.
Time Frame Baseline (pre-dose on Cycle 1 Day 1), Cycle 1 Day 15, Cycle 2 Day 15 and end of treatment (assessed up to maximum 4 years). The duration of one cycle was 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization to spartalizumab. Biomarker samples were not collected in participants randomized to chemotherapy.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 82
Median (Full Range)
Unit of Measure: fold change
Cycle 1 Day 15 Number Analyzed 65 participants
1.53
(0.2 to 14.3)
Cycle 2 Day 15 Number Analyzed 51 participants
1.31
(0.1 to 35.2)
End of treatment Number Analyzed 34 participants
1.11
(0.1 to 3.8)
19.Secondary Outcome
Title Fold Change From Baseline in IL-6 Levels in Plasma
Hide Description The levels of interleukin-6 (IL-6) were measured in plasma samples by immunoassay methods. This record summarizes the fold change from baseline in IL-6 levels in plasma.
Time Frame Baseline (pre-dose on Cycle 1 Day 1), Cycle 1 Day 15, Cycle 2 Day 15 and end of treatment (assessed up to maximum 4 years). The duration of one cycle was 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization to spartalizumab. Biomarker samples were not collected in participants randomized to chemotherapy.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 82
Median (Full Range)
Unit of Measure: fold change
Cycle 1 Day 15 Number Analyzed 41 participants
1.10
(0.2 to 3.3)
Cycle 2 Day 15 Number Analyzed 30 participants
1.35
(0.2 to 6.3)
End of treatment Number Analyzed 26 participants
1.41
(0.2 to 7.7)
20.Secondary Outcome
Title Fold Change From Baseline in TNF-alfa Levels in Plasma
Hide Description The levels of tumor necrosis factor-alpha (TNF-alfa) were measured in plasma samples by immunoassay methods. This record summarizes the fold change from baseline in TNF-alfa levels in plasma.
Time Frame Baseline (pre-dose on Cycle 1 Day 1), Cycle 1 Day 15, Cycle 2 Day 15 and end of treatment (assessed up to maximum 4 years). The duration of one cycle was 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization to spartalizumab. Biomarker samples were not collected in participants randomized to chemotherapy.
Arm/Group Title Spartalizumab 400 mg Q4W
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Overall Number of Participants Analyzed 82
Median (Full Range)
Unit of Measure: fold change
Cycle 1 Day 15 Number Analyzed 73 participants
1.32
(0.4 to 2.2)
Cycle 2 Day 15 Number Analyzed 62 participants
1.39
(0.3 to 3.1)
End of treatment Number Analyzed 45 participants
1.67
(0.3 to 3.7)
21.Post-Hoc Outcome
Title Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment in Participants Who Crossed Over - Number of Participants With Progression or Death
Hide Description

PFS is the time from the date of first dose of spartalizumab to the date of event defined as the first documented confirmed progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.

Tumor response was based on central review of tumor scan and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive disease is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. Number of participants in each category (progression, death, censored) is reported in this record.

Time Frame From first dose of spartalizumab up to maximum 0.6 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who crossed over from chemotherapy to spartalizumab.
Arm/Group Title Crossover to Spartalizumab
Hide Arm/Group Description:
Patients treated with chemotherapy who crossed over to spartalizumab
Overall Number of Participants Analyzed 27
Measure Type: Count of Participants
Unit of Measure: Participants
number of progression
20
  74.1%
number of deaths
5
  18.5%
number of censored
2
   7.4%
22.Post-Hoc Outcome
Title Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment in Participants Who Crossed Over - Median PFS
Hide Description

PFS is the time from the date of first dose of spartalizumab to the date of event defined as the first documented confirmed progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.

Tumor response was based on central review of tumor scan and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive disease is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.

Time Frame From first dose of spartalizumab up to maximum 0.6 years
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who crossed over from chemotherapy to spartalizumab.
Arm/Group Title Crossover to Spartalizumab
Hide Arm/Group Description:
Patients treated with chemotherapy who crossed over to spartalizumab
Overall Number of Participants Analyzed 27
Median (95% Confidence Interval)
Unit of Measure: months
1.7
(1.6 to 1.9)
23.Post-Hoc Outcome
Title All Collected Deaths
Hide Description

On-treatment deaths were collected from the start of treatment up to 30 days after study drug discontinuation, for a maximum duration of 4.0 years. Post-treatment deaths were collected after the on-treatment period (starting at day 31 after last dose of study treatment), up to 4.8 years.

For the crossover patients, the deaths collected before crossing over are summarized in the chemotherapy arm and the deaths collected after the crossover are summarized in the crossover arm.

Time Frame Up to 4.0 years (on-treatment deaths) and 4.8 years (all deaths).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants to whom study treatment was assigned by randomization.
Arm/Group Title Spartalizumab 400 mg Q4W Chemotherapy Crossover to Spartalizumab
Hide Arm/Group Description:
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Commonly used chemotherapy as per investigator's choice
Patients treated with chemotherapy who crossed over to spartalizumab
Overall Number of Participants Analyzed 82 40 27
Measure Type: Number
Unit of Measure: participants
Total Deaths 48 9 19
Deaths on-treatment 5 3 3
Time Frame From first dose of study treatment up to 30 days after last dose (maximum 4.0 years).
Adverse Event Reporting Description

For the crossover patients, safety data collected before crossing over is summarized in the chemotherapy arm and safety data collected after the crossover is summarized in the crossover arm.

The column 'all spartalizumab participants' summarizes the safety data of the 2 arms with spartalizumab dosing.

AEs and mortality are assessed in the safety set that includes all patients who received at least 1 dose of study medication and had at least 1 valid post-screening/post-baseline safety assessment.

 
Arm/Group Title Spartalizumab 400 mg Q4W Chemotherapy Crossover to Spartalizumab All Spartalizumab Participants
Hide Arm/Group Description anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab Commonly used chemotherapy as per investigator's choice Patients treated with chemotherapy who crossed over to spartalizumab All participants who received at least one dose of spartalizumab
All-Cause Mortality
Spartalizumab 400 mg Q4W Chemotherapy Crossover to Spartalizumab All Spartalizumab Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/82 (6.10%)   3/39 (7.69%)   3/27 (11.11%)   8/109 (7.34%) 
Hide Serious Adverse Events
Spartalizumab 400 mg Q4W Chemotherapy Crossover to Spartalizumab All Spartalizumab Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   28/82 (34.15%)   15/39 (38.46%)   12/27 (44.44%)   40/109 (36.70%) 
Blood and lymphatic system disorders         
Anaemia  1  2/82 (2.44%)  1/39 (2.56%)  1/27 (3.70%)  3/109 (2.75%) 
Febrile neutropenia  1  1/82 (1.22%)  4/39 (10.26%)  0/27 (0.00%)  1/109 (0.92%) 
Neutropenia  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Normocytic anaemia  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Thrombocytopenia  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Cardiac disorders         
Angina pectoris  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Myocardial infarction  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Pericardial effusion  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Eye disorders         
Papilloedema  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Gastrointestinal disorders         
Abdominal pain  1  1/82 (1.22%)  0/39 (0.00%)  1/27 (3.70%)  2/109 (1.83%) 
Abdominal pain upper  1  1/82 (1.22%)  0/39 (0.00%)  1/27 (3.70%)  2/109 (1.83%) 
Ascites  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Diarrhoea  1  0/82 (0.00%)  2/39 (5.13%)  0/27 (0.00%)  0/109 (0.00%) 
Duodenal ulcer  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Dysphagia  1  1/82 (1.22%)  1/39 (2.56%)  0/27 (0.00%)  1/109 (0.92%) 
Stomatitis  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Vomiting  1  1/82 (1.22%)  2/39 (5.13%)  1/27 (3.70%)  2/109 (1.83%) 
General disorders         
Asthenia  1  1/82 (1.22%)  1/39 (2.56%)  1/27 (3.70%)  2/109 (1.83%) 
Fatigue  1  0/82 (0.00%)  1/39 (2.56%)  1/27 (3.70%)  1/109 (0.92%) 
Generalised oedema  1  0/82 (0.00%)  0/39 (0.00%)  1/27 (3.70%)  1/109 (0.92%) 
Oedema peripheral  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Pain  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Peripheral swelling  1  0/82 (0.00%)  0/39 (0.00%)  1/27 (3.70%)  1/109 (0.92%) 
Pyrexia  1  3/82 (3.66%)  0/39 (0.00%)  1/27 (3.70%)  4/109 (3.67%) 
Hepatobiliary disorders         
Cholecystitis acute  1  0/82 (0.00%)  0/39 (0.00%)  1/27 (3.70%)  1/109 (0.92%) 
Hepatocellular injury  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Infections and infestations         
Brain abscess  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Conjunctivitis  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Gastroenteritis  1  1/82 (1.22%)  1/39 (2.56%)  0/27 (0.00%)  1/109 (0.92%) 
Lower respiratory tract infection  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Pneumonia  1  1/82 (1.22%)  1/39 (2.56%)  1/27 (3.70%)  2/109 (1.83%) 
Sepsis  1  2/82 (2.44%)  0/39 (0.00%)  1/27 (3.70%)  3/109 (2.75%) 
Septic shock  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Sinusitis  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Injury, poisoning and procedural complications         
Electrical burn  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Investigations         
Aspartate aminotransferase increased  1  2/82 (2.44%)  0/39 (0.00%)  0/27 (0.00%)  2/109 (1.83%) 
Bilirubin conjugated increased  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Blood bilirubin increased  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Blood bilirubin unconjugated increased  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Metabolism and nutrition disorders         
Decreased appetite  1  0/82 (0.00%)  0/39 (0.00%)  1/27 (3.70%)  1/109 (0.92%) 
Hypercalcaemia  1  0/82 (0.00%)  1/39 (2.56%)  1/27 (3.70%)  1/109 (0.92%) 
Hyperkalaemia  1  0/82 (0.00%)  0/39 (0.00%)  1/27 (3.70%)  1/109 (0.92%) 
Hypokalaemia  1  0/82 (0.00%)  2/39 (5.13%)  0/27 (0.00%)  0/109 (0.00%) 
Hyponatraemia  1  2/82 (2.44%)  0/39 (0.00%)  1/27 (3.70%)  3/109 (2.75%) 
Malnutrition  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/82 (0.00%)  0/39 (0.00%)  1/27 (3.70%)  1/109 (0.92%) 
Bone pain  1  2/82 (2.44%)  0/39 (0.00%)  0/27 (0.00%)  2/109 (1.83%) 
Muscular weakness  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Tumour associated fever  1  0/82 (0.00%)  1/39 (2.56%)  1/27 (3.70%)  1/109 (0.92%) 
Nervous system disorders         
Diplegia  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Hemiparesis  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Spinal cord compression  1  2/82 (2.44%)  1/39 (2.56%)  0/27 (0.00%)  2/109 (1.83%) 
Renal and urinary disorders         
Acute kidney injury  1  0/82 (0.00%)  0/39 (0.00%)  1/27 (3.70%)  1/109 (0.92%) 
Urinary retention  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Respiratory, thoracic and mediastinal disorders         
Acute respiratory failure  1  0/82 (0.00%)  1/39 (2.56%)  0/27 (0.00%)  0/109 (0.00%) 
Dyspnoea  1  0/82 (0.00%)  1/39 (2.56%)  2/27 (7.41%)  2/109 (1.83%) 
Epistaxis  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Nasal congestion  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Pleural effusion  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Pneumonia aspiration  1  2/82 (2.44%)  0/39 (0.00%)  1/27 (3.70%)  3/109 (2.75%) 
Pneumonitis  1  2/82 (2.44%)  0/39 (0.00%)  1/27 (3.70%)  3/109 (2.75%) 
Pneumothorax  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Skin and subcutaneous tissue disorders         
Angioedema  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Rash maculo-papular  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
Social circumstances         
Miscarriage of partner  1  1/82 (1.22%)  0/39 (0.00%)  0/27 (0.00%)  1/109 (0.92%) 
1
Term from vocabulary, MedDRA (23.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Spartalizumab 400 mg Q4W Chemotherapy Crossover to Spartalizumab All Spartalizumab Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   76/82 (92.68%)   37/39 (94.87%)   25/27 (92.59%)   101/109 (92.66%) 
Blood and lymphatic system disorders         
Anaemia  1  19/82 (23.17%)  19/39 (48.72%)  6/27 (22.22%)  25/109 (22.94%) 
Leukopenia  1  2/82 (2.44%)  3/39 (7.69%)  0/27 (0.00%)  2/109 (1.83%) 
Lymphopenia  1  0/82 (0.00%)  2/39 (5.13%)  1/27 (3.70%)  1/109 (0.92%) 
Neutropenia  1  1/82 (1.22%)  12/39 (30.77%)  0/27 (0.00%)  1/109 (0.92%) 
Thrombocytopenia  1  1/82 (1.22%)  3/39 (7.69%)  0/27 (0.00%)  1/109 (0.92%) 
Endocrine disorders         
Hypothyroidism  1  10/82 (12.20%)  2/39 (5.13%)  3/27 (11.11%)  13/109 (11.93%) 
Gastrointestinal disorders         
Abdominal discomfort  1  0/82 (0.00%)  2/39 (5.13%)  1/27 (3.70%)  1/109 (0.92%) 
Abdominal distension  1  5/82 (6.10%)  0/39 (0.00%)  1/27 (3.70%)  6/109 (5.50%) 
Abdominal pain  1  5/82 (6.10%)  2/39 (5.13%)  4/27 (14.81%)  9/109 (8.26%) 
Abdominal pain upper  1  8/82 (9.76%)  3/39 (7.69%)  3/27 (11.11%)  11/109 (10.09%) 
Constipation  1  13/82 (15.85%)  7/39 (17.95%)  3/27 (11.11%)  16/109 (14.68%) 
Diarrhoea  1  5/82 (6.10%)  5/39 (12.82%)  1/27 (3.70%)  6/109 (5.50%) 
Dry mouth  1  3/82 (3.66%)  3/39 (7.69%)  1/27 (3.70%)  4/109 (3.67%) 
Dyspepsia  1  0/82 (0.00%)  2/39 (5.13%)  1/27 (3.70%)  1/109 (0.92%) 
Dysphagia  1  5/82 (6.10%)  1/39 (2.56%)  0/27 (0.00%)  5/109 (4.59%) 
Mouth ulceration  1  0/82 (0.00%)  2/39 (5.13%)  0/27 (0.00%)  0/109 (0.00%) 
Nausea  1  13/82 (15.85%)  8/39 (20.51%)  4/27 (14.81%)  17/109 (15.60%) 
Oral pain  1  0/82 (0.00%)  2/39 (5.13%)  0/27 (0.00%)  0/109 (0.00%) 
Stomatitis  1  6/82 (7.32%)  9/39 (23.08%)  0/27 (0.00%)  6/109 (5.50%) 
Vomiting  1  14/82 (17.07%)  6/39 (15.38%)  7/27 (25.93%)  21/109 (19.27%) 
General disorders         
Asthenia  1  11/82 (13.41%)  2/39 (5.13%)  1/27 (3.70%)  12/109 (11.01%) 
Fatigue  1  14/82 (17.07%)  15/39 (38.46%)  5/27 (18.52%)  19/109 (17.43%) 
Malaise  1  6/82 (7.32%)  2/39 (5.13%)  1/27 (3.70%)  7/109 (6.42%) 
Oedema peripheral  1  2/82 (2.44%)  5/39 (12.82%)  0/27 (0.00%)  2/109 (1.83%) 
Peripheral swelling  1  0/82 (0.00%)  0/39 (0.00%)  2/27 (7.41%)  2/109 (1.83%) 
Pyrexia  1  16/82 (19.51%)  3/39 (7.69%)  8/27 (29.63%)  24/109 (22.02%) 
Swelling face  1  0/82 (0.00%)  3/39 (7.69%)  1/27 (3.70%)  1/109 (0.92%) 
Infections and infestations         
Herpes zoster  1  3/82 (3.66%)  2/39 (5.13%)  0/27 (0.00%)  3/109 (2.75%) 
Nasopharyngitis  1  3/82 (3.66%)  2/39 (5.13%)  0/27 (0.00%)  3/109 (2.75%) 
Pneumonia  1  3/82 (3.66%)  2/39 (5.13%)  0/27 (0.00%)  3/109 (2.75%) 
Sinusitis  1  1/82 (1.22%)  2/39 (5.13%)  0/27 (0.00%)  1/109 (0.92%) 
Upper respiratory tract infection  1  9/82 (10.98%)  2/39 (5.13%)  1/27 (3.70%)  10/109 (9.17%) 
Urinary tract infection  1  1/82 (1.22%)  2/39 (5.13%)  0/27 (0.00%)  1/109 (0.92%) 
Investigations         
Alanine aminotransferase increased  1  7/82 (8.54%)  6/39 (15.38%)  1/27 (3.70%)  8/109 (7.34%) 
Aspartate aminotransferase increased  1  15/82 (18.29%)  7/39 (17.95%)  2/27 (7.41%)  17/109 (15.60%) 
Blood alkaline phosphatase increased  1  4/82 (4.88%)  1/39 (2.56%)  2/27 (7.41%)  6/109 (5.50%) 
Blood creatinine increased  1  5/82 (6.10%)  2/39 (5.13%)  1/27 (3.70%)  6/109 (5.50%) 
Blood thyroid stimulating hormone increased  1  6/82 (7.32%)  1/39 (2.56%)  0/27 (0.00%)  6/109 (5.50%) 
Lymphocyte count decreased  1  3/82 (3.66%)  2/39 (5.13%)  1/27 (3.70%)  4/109 (3.67%) 
Neutrophil count decreased  1  1/82 (1.22%)  2/39 (5.13%)  0/27 (0.00%)  1/109 (0.92%) 
Platelet count decreased  1  1/82 (1.22%)  7/39 (17.95%)  2/27 (7.41%)  3/109 (2.75%) 
Weight decreased  1  9/82 (10.98%)  5/39 (12.82%)  0/27 (0.00%)  9/109 (8.26%) 
White blood cell count decreased  1  1/82 (1.22%)  8/39 (20.51%)  0/27 (0.00%)  1/109 (0.92%) 
Metabolism and nutrition disorders         
Decreased appetite  1  16/82 (19.51%)  9/39 (23.08%)  8/27 (29.63%)  24/109 (22.02%) 
Dehydration  1  3/82 (3.66%)  2/39 (5.13%)  0/27 (0.00%)  3/109 (2.75%) 
Hyperglycaemia  1  5/82 (6.10%)  1/39 (2.56%)  0/27 (0.00%)  5/109 (4.59%) 
Hypoalbuminaemia  1  6/82 (7.32%)  2/39 (5.13%)  3/27 (11.11%)  9/109 (8.26%) 
Hypokalaemia  1  5/82 (6.10%)  13/39 (33.33%)  4/27 (14.81%)  9/109 (8.26%) 
Hypomagnesaemia  1  7/82 (8.54%)  6/39 (15.38%)  2/27 (7.41%)  9/109 (8.26%) 
Hyponatraemia  1  14/82 (17.07%)  6/39 (15.38%)  4/27 (14.81%)  18/109 (16.51%) 
Hypophosphataemia  1  0/82 (0.00%)  2/39 (5.13%)  1/27 (3.70%)  1/109 (0.92%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  9/82 (10.98%)  2/39 (5.13%)  5/27 (18.52%)  14/109 (12.84%) 
Back pain  1  9/82 (10.98%)  6/39 (15.38%)  4/27 (14.81%)  13/109 (11.93%) 
Bone pain  1  4/82 (4.88%)  2/39 (5.13%)  1/27 (3.70%)  5/109 (4.59%) 
Muscular weakness  1  2/82 (2.44%)  2/39 (5.13%)  0/27 (0.00%)  2/109 (1.83%) 
Musculoskeletal chest pain  1  4/82 (4.88%)  3/39 (7.69%)  0/27 (0.00%)  4/109 (3.67%) 
Myalgia  1  1/82 (1.22%)  3/39 (7.69%)  0/27 (0.00%)  1/109 (0.92%) 
Nervous system disorders         
Dizziness  1  5/82 (6.10%)  1/39 (2.56%)  3/27 (11.11%)  8/109 (7.34%) 
Headache  1  12/82 (14.63%)  4/39 (10.26%)  1/27 (3.70%)  13/109 (11.93%) 
Hypoaesthesia  1  4/82 (4.88%)  5/39 (12.82%)  2/27 (7.41%)  6/109 (5.50%) 
Neuropathy peripheral  1  3/82 (3.66%)  5/39 (12.82%)  2/27 (7.41%)  5/109 (4.59%) 
Peripheral sensory neuropathy  1  0/82 (0.00%)  4/39 (10.26%)  0/27 (0.00%)  0/109 (0.00%) 
Psychiatric disorders         
Insomnia  1  9/82 (10.98%)  3/39 (7.69%)  3/27 (11.11%)  12/109 (11.01%) 
Renal and urinary disorders         
Urinary retention  1  0/82 (0.00%)  0/39 (0.00%)  2/27 (7.41%)  2/109 (1.83%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  17/82 (20.73%)  12/39 (30.77%)  1/27 (3.70%)  18/109 (16.51%) 
Dysphonia  1  4/82 (4.88%)  2/39 (5.13%)  0/27 (0.00%)  4/109 (3.67%) 
Dyspnoea  1  12/82 (14.63%)  3/39 (7.69%)  3/27 (11.11%)  15/109 (13.76%) 
Epistaxis  1  10/82 (12.20%)  3/39 (7.69%)  0/27 (0.00%)  10/109 (9.17%) 
Nasal congestion  1  3/82 (3.66%)  2/39 (5.13%)  1/27 (3.70%)  4/109 (3.67%) 
Pleural effusion  1  2/82 (2.44%)  0/39 (0.00%)  3/27 (11.11%)  5/109 (4.59%) 
Productive cough  1  1/82 (1.22%)  2/39 (5.13%)  1/27 (3.70%)  2/109 (1.83%) 
Rhinorrhoea  1  2/82 (2.44%)  3/39 (7.69%)  1/27 (3.70%)  3/109 (2.75%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  0/82 (0.00%)  9/39 (23.08%)  0/27 (0.00%)  0/109 (0.00%) 
Dry skin  1  5/82 (6.10%)  0/39 (0.00%)  2/27 (7.41%)  7/109 (6.42%) 
Palmar-plantar erythrodysaesthesia syndrome  1  0/82 (0.00%)  6/39 (15.38%)  1/27 (3.70%)  1/109 (0.92%) 
Pruritus  1  10/82 (12.20%)  3/39 (7.69%)  4/27 (14.81%)  14/109 (12.84%) 
Rash  1  15/82 (18.29%)  6/39 (15.38%)  1/27 (3.70%)  16/109 (14.68%) 
Urticaria  1  0/82 (0.00%)  2/39 (5.13%)  0/27 (0.00%)  0/109 (0.00%) 
Vascular disorders         
Hypertension  1  1/82 (1.22%)  2/39 (5.13%)  2/27 (7.41%)  3/109 (2.75%) 
1
Term from vocabulary, MedDRA (23.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
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Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: novartis.email@novartis.com
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Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02605967    
Other Study ID Numbers: CPDR001X2201
2015-000454-38 ( EudraCT Number )
First Submitted: October 15, 2015
First Posted: November 17, 2015
Results First Submitted: April 21, 2021
Results First Posted: August 12, 2021
Last Update Posted: February 10, 2022