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Phase I/II Study of PDR001 in Patients With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT02404441
Recruitment Status : Completed
First Posted : March 31, 2015
Results First Posted : September 29, 2021
Last Update Posted : September 29, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Melanoma
Non-small Sell Lung Cancer (NSCLC)
Triple Negative Breast Cancer
Anaplastic Thyroid Cancer
Other Solid Tumors
Intervention Biological: PDR001
Enrollment 319
Recruitment Details 58 patients were analyzed in Phase l and 261 patients were analyzed in Phase II of this study.
Pre-assignment Details The study planned to analyze about 58 patients in Phase I and about 120 patients in Phase II.
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w 3mg/kg q4w 5mg/kg q4w NSCLC 400mg/q4w Melanoma 400mg/q4w TNBC 400mg/q4w NSCLC 300mg/q3w ATC 400 mg/q4w
Hide Arm/Group Description Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w Phase I Dose escalation cohort patients who took PRD001 10 mg/kg q2w Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w Phase II: non-small cell cancer patients who took PDR001 400 mg/q4w Phase II: Melanoma patients who took PDR001 400 mg/q4w Phase II: Triple negative breast cancer (TNBC) patients who took PDR001 400 mg/q4w Phase II: non-small cell cancer patients who took PDR001 300 mg/q3w Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
Period Title: Phase 1 Part
Started 16 15 11 6 10 0 0 0 0 0
Completed [1] 0 0 0 0 0 0 0 0 0 0
Not Completed 16 15 11 6 10 0 0 0 0 0
Reason Not Completed
Adverse Event             1             0             0             0             0             0             0             0             0             0
Physician Decision             0             1             0             0             0             0             0             0             0             0
Progressive Disease             14             11             7             6             9             0             0             0             0             0
Subject/Guardian Decision             0             2             3             0             0             0             0             0             0             0
Death             1             1             1             0             1             0             0             0             0             0
[1]
Completed = Treatment Discontinued
Period Title: Phase 2 Part
Started 0 0 0 0 0 59 61 40 59 42
Entered Post-treatment Follow-up 0 0 0 0 0 2 6 1 6 1
No Longer Being Followed for Post-treatment Follow-up 0 0 0 0 0 2 6 1 6 1
Entered Survival Follow-up 0 0 0 0 0 38 34 26 35 25
Completed [1] 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 59 61 40 59 42
Reason Not Completed
Adverse Event             0             0             0             0             0             2             3             3             6             1
Physician Decision             0             0             0             0             0             7             9             2             1             3
Progressive disease             0             0             0             0             0             43             32             31             39             27
Subject/guardian decision             0             0             0             0             0             3             9             0             3             2
Death             0             0             0             0             0             4             8             4             10             9
[1]
Completed = Treatment Discontinued
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w 3mg/kg q4w 5mg/kg q4w NSCLC 400mg/q4w Melanoma 400mg/q4w TNBC 400mg/q4w NSCLC 300mg/q3w ATC 400 mg/q4w Total
Hide Arm/Group Description Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w Phase II: non-small cell cancer patients who took PDR001 400 mg/q4w Phase II: Melanoma patients who took PDR001 400 mg/q4w Phase II: Triple negative breast cancer (TNBC) patients who took PDR001 400 mg/q4w Phase II: non-small cell cancer patients who took PDR001 300 mg/q3w Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w Total of all reporting groups
Overall Number of Baseline Participants 16 15 11 6 10 59 61 40 59 42 319
Hide Baseline Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants 15 participants 11 participants 6 participants 10 participants 59 participants 61 participants 40 participants 59 participants 42 participants 319 participants
< 65 years 12 9 8 6 8 33 37 29 35 25 202
≥ 65years 4 6 3 0 2 26 24 11 24 17 117
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 15 participants 11 participants 6 participants 10 participants 59 participants 61 participants 40 participants 59 participants 42 participants 319 participants
Female
9
  56.3%
7
  46.7%
4
  36.4%
2
  33.3%
4
  40.0%
23
  39.0%
22
  36.1%
40
 100.0%
20
  33.9%
19
  45.2%
150
  47.0%
Male
7
  43.8%
8
  53.3%
7
  63.6%
4
  66.7%
6
  60.0%
36
  61.0%
39
  63.9%
0
   0.0%
39
  66.1%
23
  54.8%
169
  53.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants 15 participants 11 participants 6 participants 10 participants 59 participants 61 participants 40 participants 59 participants 42 participants 319 participants
Caucasian 10 14 8 4 8 42 37 32 50 33 238
Black 2 0 0 0 0 0 1 1 0 1 5
Asian 3 1 2 2 1 12 23 4 8 4 60
Unknown 1 0 0 0 0 5 0 2 1 4 13
Other 0 0 1 0 1 0 0 1 0 0 3
1.Primary Outcome
Title Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days)
Hide Description

Estimated the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) for PDR001.

AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time.

Time Frame Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 3)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w 3mg/kg q4w 5mg/kg q4w
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Overall Number of Participants Analyzed 8 4 4 3 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: day*ug/mL
270
(52.5%)
1150
(51.1%)
3110
(33.1%)
575
(21.8%)
1490
(34.2%)
2.Primary Outcome
Title Phase l: Incidence of Dose Limiting Toxicities (DLTs)
Hide Description DLT is defined as an adverse event (AE) or abnormal laboratory value of common terminology criteria for adverse events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first cycle of treatment with PDR001 during the dose escalation part of the study for which relationship to study treatment cannot be ruled out, with some exceptions.
Time Frame 8 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set: The Safety Set included all subjects from the FAS who received at least one dose of spartalizumab and had at least one valid post-baseline safety assessment.
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w 3mg/kg q4w 5mg/kg q4w
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Overall Number of Participants Analyzed 16 15 11 6 10
Measure Type: Number
Unit of Measure: Participants
0 0 0 0 0
3.Primary Outcome
Title Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Hide Description

ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required.

PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required.

RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.

Time Frame 61 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title NSCLC 400 mg/q4w Melanoma 400 mg/q4w TNBC 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w All Phase II Patients
Hide Arm/Group Description:
Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with TNBC who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
All patients in Phase II regardless of how they took PDR001
Overall Number of Participants Analyzed 59 61 40 59 42 261
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
15.3
(8.2 to 25.1)
27.9
(18.6 to 38.8)
0.0
(0.0 to 7.2)
6.8
(2.3 to 14.8)
19.0
(9.8 to 31.8)
14.6
(11.1 to 18.6)
4.Secondary Outcome
Title Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau)
Hide Description

AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time.

AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1).

AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).

Time Frame Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w 3mg/kg q4w 5mg/kg q4w
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Overall Number of Participants Analyzed 16 15 11 6 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: day*ug/mL
Cycle (C) 1: AUC0-336h (n=16, 13, 10, 6, 10) Number Analyzed 16 participants 13 participants 10 participants 6 participants 10 participants
126
(29.5%)
324
(24.4%)
1270
(20.3%)
350
(35.0%)
638
(35.3%)
C1: AUCinf (n = 1, 0,0,2,3) Number Analyzed 1 participants 0 participants 0 participants 2 participants 3 participants
123
(0%)
384
(9.8%)
726
(16.0%)
C1: AUClast Number Analyzed 16 participants 15 participants 11 participants 6 participants 10 participants
125
(29.9%)
353
(31.4%)
1240
(21.6%)
522
(39.1%)
943
(37.4%)
C1: AUCtau (n = 16, 13, 10, 6, 10) Number Analyzed 16 participants 13 participants 10 participants 6 participants 10 participants
126
(29.5%)
324
(24.4%)
1270
(20.3%)
524
(39.6%)
984
(41.9%)
C3: AUClast Number Analyzed 11 participants 9 participants 5 participants 3 participants 4 participants
260
(44.8%)
995
(60.5%)
2520
(58.4%)
933
(21.3%)
2560
(37.2%)
C3: AUCtau (n = 8, 4, 4, 2, 2) Number Analyzed 8 participants 4 participants 4 participants 2 participants 2 participants
270
(52.5%)
1150
(51.1%)
3110
(33.1%)
1040
(19.1%)
2770
(26.6%)
5.Secondary Outcome
Title Phase I: Serum Pharmacokinetic (PK) Parameter Cmax
Hide Description The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
Time Frame Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w 3mg/kg q4w 5mg/kg q4w
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Overall Number of Participants Analyzed 16 15 11 6 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ug/mL
C1 (n = 15, 15, 10, 6, 9) Number Analyzed 15 participants 15 participants 10 participants 6 participants 9 participants
18.2
(26.5%)
53.8
(23.6%)
185
(18.3%)
53.8
(29.4%)
106
(34.2%)
C3 (n = 10, 7, 3, 3, 2) Number Analyzed 10 participants 7 participants 3 participants 3 participants 2 participants
29.7
(41.0%)
112
(27.3%)
312
(30.0%)
69.7
(9.4%)
179
(45.2%)
6.Secondary Outcome
Title Phase I: Serum Pharmacokinetic (PK) Parameter Tmax
Hide Description The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
Time Frame Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w 3mg/kg q4w 5mg/kg q4w
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Overall Number of Participants Analyzed 16 15 11 6 10
Median (Full Range)
Unit of Measure: hour
C1 (n = 15, 15, 10, 6, 9) Number Analyzed 15 participants 15 participants 10 participants 6 participants 9 participants
1.58
(1.38 to 2.12)
1.57
(1.25 to 1.7)
1.55
(1.13 to 1.68)
1.55
(1.5 to 1.83)
1.58
(1.08 to 1.67)
C3 (n = 10, 7, 3, 3, 2) Number Analyzed 10 participants 7 participants 3 participants 3 participants 2 participants
1.55
(1.45 to 1.75)
1.55
(0.75 to 1.58)
1.58
(1.52 to 1.62)
1.5
(1.5 to 1.57)
1.3
(0.783 to 1.82)
7.Secondary Outcome
Title Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau)
Hide Description

AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time.

AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1).

AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).

Time Frame Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
Arm/Group Title NSCLC 400 mg/q4w Melanoma 400 mg/q4w TNBC 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w
Hide Arm/Group Description:
Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with TNBC who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
Overall Number of Participants Analyzed 59 61 40 59 42
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: day*ug/mL
C1: AUC0-336h (n =58, 58, 37, 54, 37) Number Analyzed 58 participants 58 participants 37 participants 54 participants 37 participants
681
(39.4%)
775
(31.7%)
752
(29.3%)
535
(38.3%)
704
(28.2%)
C1: AUCinf (n = 13, 8, 7, 5, 2) Number Analyzed 13 participants 8 participants 7 participants 5 participants 2 participants
1090
(29.6%)
1080
(45.4%)
1240
(25.2%)
491
(22.7%)
1160
(7.1%)
C1: AUClast Number Analyzed 59 participants 61 participants 40 participants 59 participants 42 participants
980
(42.5%)
1020
(109.9%)
923
(76.1%)
602
(62.2%)
865
(69.8%)
C1: AUCtau (n= 54, 55, 32, 48, 36) Number Analyzed 54 participants 55 participants 32 participants 48 participants 36 participants
1010
(39.8%)
1190
(35.0%)
1130
(34.9%)
689
(40.4%)
1070
(31.3%)
C3: AUC0-336h (n = 36, 49, 12, 40, 16) Number Analyzed 36 participants 49 participants 12 participants 40 participants 16 participants
1210
(36.3%)
1140
(43.8%)
1360
(45.7%)
850
(50.6%)
1290
(30.0%)
C3: AUCinf (n = 1, 1, 1, 1, 0) Number Analyzed 1 participants 1 participants 1 participants 1 participants 0 participants
1050 [1] 
(NA%)
1070 [1] 
(NA%)
2340 [1] 
(NA%)
135 [1] 
(NA%)
C3: AUClast (n = 37, 51, 16, 44, 19) Number Analyzed 37 participants 51 participants 16 participants 44 participants 19 participants
1860
(39.9%)
1650
(59.7%)
1630
(73.4%)
984
(78.0%)
1600
(88.0%)
C3: AUCtau (n= 31, 44, 7, 38, 14) Number Analyzed 31 participants 44 participants 7 participants 38 participants 14 participants
1940
(35.5%)
1790
(53.4%)
1920
(44.4%)
1100
(54.5%)
2120
(32.7%)
[1]
N/A = Geometric coefficient of variation could not be calculated as there was only 1 patient
8.Secondary Outcome
Title Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax
Hide Description The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
Time Frame Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
Arm/Group Title NSCLC 400 mg/q4w Melanoma 400 mg/q4w TNBC 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w
Hide Arm/Group Description:
Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with TNBC who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
Overall Number of Participants Analyzed 59 61 40 59 42
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ug/mL
C1 (n = 52, 58, 32, 55, 35) Number Analyzed 52 participants 58 participants 32 participants 55 participants 35 participants
103
(37.0%)
111
(26.6%)
114
(23.6%)
79.9
(31.8%)
100
(27.3%)
C3 (n = 33, 45, 11, 39, 18) Number Analyzed 33 participants 45 participants 11 participants 39 participants 18 participants
151
(32.0%)
141
(33.4%)
163
(34.7%)
103
(36.6%)
146
(22.6%)
9.Secondary Outcome
Title Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax
Hide Description The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
Time Frame Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
Arm/Group Title NSCLC 400 mg/q4w Melanoma 400 mg/q4w TNBC 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w
Hide Arm/Group Description:
Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with TNBC who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
Overall Number of Participants Analyzed 59 61 40 59 42
Median (Full Range)
Unit of Measure: hour
C1 (n= 52, 58, 32, 55, 35) Number Analyzed 52 participants 58 participants 32 participants 55 participants 35 participants
1.58
(0.55 to 2.52)
1.58
(1.07 to 2.9)
1.58
(1.18 to 2.15)
1.65
(1.00 to 3.08)
1.55
(0.5 to 2.75)
C3 (n = 33, 45, 11, 39, 18) Number Analyzed 33 participants 45 participants 11 participants 39 participants 18 participants
1.6
(0.983 to 2.08)
1.55
(1.07 to 2.22)
1.53
(1.42 to 1.62)
1.58
(1.33 to 2.92)
1.57
(0 to 4.63)
10.Secondary Outcome
Title Phase I: Presence and/or Concentration of Anti-PDR001
Hide Description Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description

Immunogenicity incidence Set: The Immunogenicity incidence set includes all subjects in FAS with a determinant baseline immunoglobulin (IG) sample and at least one determinant post-baseline IG sample.

Treatment-induced ADA-positive was performed on ADA-positive patients only. Treatment-boosted ADA-positive was performed on ADA-positive patients only.

Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w All Phase I q2w 3mg/kg q4w 5mg/kg q4w All Phase I q4w All Phase I Patients
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w
Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Phase I dose Cohorts - All patients in Phase I who took PDR001 q4w
All patients in Phase I regardless of how they took PDR001
Overall Number of Participants Analyzed 16 11 3 30 6 10 16 46
Measure Type: Number
Unit of Measure: Participants
Patients with ADA-negative sample at baseline 11 9 1 21 5 9 14 35
Patients with ADA-positive sample at baseline 5 2 2 9 1 1 2 11
ADA-negative 10 8 1 19 4 8 12 31
ADA-positive (i.e., ADA incidence) 4 2 2 8 1 1 2 10
Treatment-induced ADA-positive 1 1 0 2 1 1 2 4
Treatment-boosted ADA-positive 3 1 2 6 0 0 0 6
11.Secondary Outcome
Title Phase II: Presence and/or Concentration of Anti-PDR001
Hide Description

Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment.

For Treatment -induced ADA-positive, Percentage was based on subjects ADA-negative at baseline.

For Treatment-boosted ADA-positive, Percentage was based on subjects ADA-positive at baseline.

Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
Immunogenicity incidence Set: The Immunogenicity incidence set includes all subjects in FAS with a determinant baseline immunoglobulin (IG) sample and at least one determinant post-baseline IG sample.
Arm/Group Title NSCLC 400 mg/q4w Melanoma 400 mg/q4w TNBC 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w All Phase II Patients
Hide Arm/Group Description:
Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with TNBC who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
All patients in Phase II regardless of how they took PDR001
Overall Number of Participants Analyzed 52 54 33 46 31 216
Measure Type: Number
Unit of Measure: Participants
Patients with ADA-negative sample at baseline 43 48 29 41 29 190
Patients with ADA-positive sample at baseline 9 6 4 5 2 26
ADA-negative 34 46 23 31 24 158
ADA-positive (i.e., ADA incidence) 11 4 7 12 6 40
Treatment-induced ADA-positive 9 2 6 10 5 32
Treatment-boosted ADA-positive 2 2 1 2 1 8
12.Secondary Outcome
Title Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1
Hide Description

ORR is the percentage of participants with a best overall response of complete response CR or partial response PR as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required.

PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.

RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.

Time Frame 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w All Phase I q2w 3mg/kg q4w 5mg/kg q4w All Phase I q4w All Phase I Patients
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w
Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Phase I dose Cohorts - All patients in Phase I who took PDR001 q4w
All patients in Phase I regardless of how they took PDR001
Overall Number of Participants Analyzed 16 15 11 42 6 10 16 58
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
0.00
(0.0 to 17.1)
6.7
(0.3 to 27.9)
9.1
(0.5 to 36.4)
4.8
(0.9 to 14.2)
0.0
(0.0 to 39.3)
0.0
(0.0 to 25.9)
0.0
(0.0 to 17.1)
3.4
(0.6 to 10.5)
13.Secondary Outcome
Title Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1
Hide Description

DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD).

CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.

SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR).

RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.

Time Frame 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w All Phase I q2w 3mg/kg q4w 5mg/kg q4w All Phase I q4w All Phase I Patients
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w
Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Phase I dose Cohorts - All patients in Phase I who took PDR001 q4w
All patients in Phase I regardless of how they took PDR001
Overall Number of Participants Analyzed 16 15 11 42 6 10 16 58
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
56.3
(33.3 to 77.3)
46.7
(24.4 to 70.0)
27.3
(7.9 to 56.4)
45.2
(32.0 to 59.0)
50.0
(15.3 to 84.7)
20.0
(3.7 to 50.7)
31.3
(13.2 to 54.8)
41.4
(30.4 to 53.0)
14.Secondary Outcome
Title Phase l: Progression Free Survival (PFS) as Per RECIST v1.1
Hide Description

PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates.

RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.

RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.

Time Frame 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w 3mg/kg q4w 5mg/kg q4w
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Overall Number of Participants Analyzed 16 15 6 11 10
Median (90% Confidence Interval)
Unit of Measure: Percentage of participants
3.5
(1.8 to 6.5)
1.9
(1.5 to 8.1)
2.2
(1.7 to 5.8)
2.7
(1.1 to 3.5)
1.8
(1.1 to 1.8)
15.Secondary Outcome
Title Phase I: Duration of Response (DOR) as Per RECIST v1.1
Hide Description DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented. CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required; PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required; PD =progression <= 12 weeks after randomization/start of treatment (and not qualifying for CR, PR or SD). SD = at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment
Time Frame 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set - Dose escalation
Arm/Group Title 3mg/kg q2w 10mg/kg q2w All Phase I q2w All Phase I Patients
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 10 mg/kg q2w
Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w
All patients in Phase I regardless of how they took PDR001
Overall Number of Participants Analyzed 1 1 2 2
Mean (Full Range)
Unit of Measure: days
261.00
(261.0 to 261.0)
55.00
(55.0 to 55.0)
158.00
(55.0 to 261.0)
158.00
(55.0 to 261.0)
16.Secondary Outcome
Title Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC)
Hide Description

ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per irRC.

CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required.

PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.

The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.

Time Frame 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w All Phase I q2w 3mg/kg q4w 5mg/kg q4w All Phase I q4w All Phase I Patients
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 10 mg/kg q2w
Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Phase I dose Cohorts - All patients in Phase I who took PDR001 q4w
All patients in Phase I regardless of how they took PDR001
Overall Number of Participants Analyzed 16 15 11 42 6 10 16 58
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
0.00
(0.0 to 17.1)
6.7
(0.3 to 27.9)
9.1
(0.5 to 36.4)
4.8
(0.9 to 14.2)
0.0
(0.0 to 39.3)
0.0
(0.0 to 25.9)
0.0
(0.0 to 17.1)
3.4
(0.6 to 10.5)
17.Secondary Outcome
Title Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC
Hide Description

DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD).

CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.

SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR).

The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.

Time Frame 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w All Phase I q2w 3mg/kg q4w 5mg/kg q4w All Phase I q4w All Phase I Patients
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 10 mg/kg q2w
Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Phase I dose Cohorts - All patients in Phase I who took PDR001 q4w
All patients in Phase I regardless of how they took PDR001
Overall Number of Participants Analyzed 16 15 11 42 6 10 16 58
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
62.5
(39.1 to 82.2)
53.3
(30.0 to 75.6)
27.3
(7.9 to 56.4)
50.0
(36.5 to 63.5)
50.0
(15.3 to 84.7)
30.0
(8.7 to 60.7)
37.5
(17.8 to 60.9)
46.6
(35.3 to 58.1)
18.Secondary Outcome
Title Phase l Only: Progression Free Survival (PFS) as Per irRC
Hide Description

PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates.

The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.

Time Frame 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w 3mg/kg q4w 5mg/kg q4w
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Overall Number of Participants Analyzed 16 15 11 11 10
Median (90% Confidence Interval)
Unit of Measure: Percentage of participants
3.6 [1] 
(1.8 to NA)
2.7
(1.5 to 8.1)
2.2
(1.7 to 5.8)
2.7
(1.1 to 5.2)
1.8
(1.1 to 2.8)
[1]
N/A: Model could not compute the upper limit of CI due to small sample size
19.Secondary Outcome
Title Phase I: Duration of Response (DOR) as Per irRC
Hide Description DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression <= start of treatment (& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug
Time Frame 61 Days
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set - Dose escalation
Arm/Group Title 3mg/kg q2w 10mg/kg q2w All Phase I q2w All Phase I Patients
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 10 mg/kg q2w
Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w
All patients in Phase I regardless of how they took PDR001
Overall Number of Participants Analyzed 1 1 2 2
Mean (Full Range)
Unit of Measure: days
261.00
(261.0 to 261.0)
55.00
(55.0 to 55.0)
158.00
(55.0 to 261.0)
158.00
(55.0 to 261.0)
20.Secondary Outcome
Title Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1
Hide Description

DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD).

CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.

SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR).

RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.

Time Frame 61 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title NSCLC 400 mg/q4w Melanoma 400 mg/q4w TNBC 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w All Phase II Patients
Hide Arm/Group Description:
Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with TNBC who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
All patients in Phase II regardless of how they took PDR001
Overall Number of Participants Analyzed 59 61 40 59 42 261
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
49.2
(37.8 to 60.5)
62.3
(51.0 to 72.7)
20.0
(10.4 to 33.2)
35.6
(25.2 to 47.1)
31.0
(19.4 to 44.6)
41.8
(36.6 to 47.0)
21.Secondary Outcome
Title Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1
Hide Description

PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates.

RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.

Time Frame 61 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title NSCLC 400 mg/q4w Melanoma 400 mg/q4w TNBC 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w
Hide Arm/Group Description:
Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with TNBC who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
Overall Number of Participants Analyzed 59 61 40 59 42
Median (90% Confidence Interval)
Unit of Measure: Percentage of participants
2.7
(1.9 to 5.4)
4.7
(3.5 to 5.6)
1.7
(1.7 to 1.8)
1.9
(1.8 to 2.1)
1.7
(1.4 to 1.9)
22.Secondary Outcome
Title Phase II: Duration of Response (DOR) as Per Investigator Based on RECIST v1.1
Hide Description

DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented.

CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.

PD = progression <= start of treatment (and not qualifying for CR, PR or SD). SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR).

RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.

Time Frame 61 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title NSCLC 400 mg/q4w Melanoma 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w
Hide Arm/Group Description:
Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
Overall Number of Participants Analyzed 9 17 4 8
Mean (Full Range)
Unit of Measure: months
5.6
(3.9 to 16.6)
32.0 [1] 
(11.1 to NA)
10.9 [2] 
(3.7 to NA)
22.8 [2] 
(5.7 to NA)
[1]
N/A = Model could not compute the upper limit of CI due to small sample size'
[2]
N/A = Model could not compute the upper limit of CI due to small sample size
23.Secondary Outcome
Title Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC
Hide Description

ORR is the percentage of participants with a best overall response CR or PR as per irRC.

CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required.

PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.

The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.

Time Frame 61 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title NSCLC 400 mg/q4w Melanoma 400 mg/q4w TNBC 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w All Phase II Patients
Hide Arm/Group Description:
Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with TNBC who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
All patients in Phase II regardless of how they took PDR001
Overall Number of Participants Analyzed 59 61 40 59 42 261
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
18.6
(10.8 to 29.0)
31.1
(21.5 to 42.3)
0.0
(0.0 to 7.2)
8.5
(3.4 to 17.0)
23.8
(13.5 to 37.0)
17.2
(13.5 to 21.6)
24.Secondary Outcome
Title Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC
Hide Description

DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD).

CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.

SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR).

The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.

Time Frame 61 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title NSCLC 400 mg/q4w Melanoma 400 mg/q4w TNBC 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w All Phase II Patients
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Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with TNBC who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
All patients in Phase II regardless of how they took PDR001
Overall Number of Participants Analyzed 59 61 40 59 42 261
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
55.9
(44.4 to 67.0)
67.2
(56.0 to 77.1)
22.5
(12.3 to 36.0)
39.0
(28.3 to 50.5)
35.7
(23.5 to 49.5)
46.4
(41.1 to 51.6)
25.Secondary Outcome
Title Phase II: Progression Free Survival (PFS) Per irRC
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PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates.

The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.

Time Frame 61 months
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Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title NSCLC 400 mg/q4w Melanoma 400 mg/q4w TNBC 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w
Hide Arm/Group Description:
Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with TNBC who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
Overall Number of Participants Analyzed 59 61 40 59 42
Median (90% Confidence Interval)
Unit of Measure: Percentage of participants
3.7
(2.6 to 7.1)
5.4
(3.7 to 6.5)
1.8
(1.7 to 1.8)
2.0
(1.8 to 2.2)
1.7
(1.4 to 1.9)
26.Secondary Outcome
Title Phase II: Duration of Response (DOR) Per irRC
Hide Description DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression <= start of treatment (& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug
Time Frame 61 months
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Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
Arm/Group Title NSCLC 400 mg/q4w Melanoma 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w
Hide Arm/Group Description:
Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
Overall Number of Participants Analyzed 11 19 5 10
Mean (Full Range)
Unit of Measure: months
5.6
(5.3 to 16.6)
32.0 [1] 
(15.6 to NA)
10.9 [1] 
(3.7 to NA)
22.1 [2] 
(3.8 to NA)
[1]
N/A = Model could not compute the upper limit of CI due to small sample size
[2]
N/A = Model could not compute the upper limit of CI due to sparse data
27.Post-Hoc Outcome
Title All Collected Deaths
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On treatment deaths were collected from the start of study treatment up to 30 days after last study treatment exposure, for a maximum duration of 114.3 weeks for Phase I part (treatment duration ranged from 2 to 110.3 weeks) and a maximum duration of 194.9 weeks for Phase II part (treatment duration ranged from 0.6 tp 190.9 weeks).

Total deaths were collected from the start of treatment up to end of follow-up phase (approx. 70 months).

Time Frame On treatment deaths: approx. 114.3 weeks (Phase I) & 194.9 weeks (phase II), all deaths: approx. 70 months
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Clinical database population: All treated patients
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w 3mg/kg q4w 5mg/kg q4w NSCLC 400 mg/q4w Melanoma 400 mg/q4w TNBC 400 mg/q4w NSCLC 300 mg/q3w ATC 400 mg/q4w
Hide Arm/Group Description:
Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w
Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w
Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w
Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w
Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w
Patients in Phase II with Melanoma who took PDR001 400 mg/q4w
Patients in Phase II with TNBC who took PDR001 400 mg/q4w
Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w
Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w
Overall Number of Participants Analyzed 16 15 11 6 10 59 61 40 59 42
Measure Type: Number
Unit of Measure: Participants
On-treatment deaths 2 2 1 1 2 4 4 4 12 11
Total deaths 10 10 6 4 7 39 32 28 47 31
Time Frame On treatment deaths were collected from the start of study treatment up to 30 days after last study treatment exposure, for a maximum duration of 114.3 weeks for the Part I phase (treatment duration ranged from 2 to 110.3 weeks) and for a maximum duration of 194.9 weeks for the Phase II part (treatment duration ranged from 0.6 to 190.9 weeks).
Adverse Event Reporting Description AE: Any sign or symptom that occurs during treatment plus 30 days post treatment.
 
Arm/Group Title 1mg/kg q2w 3mg/kg q2w 10mg/kg q2w All Phase I q2w 3mg/kg q4w 5mg/kg q4w All Phase I q4w All Phase I Patients NSCLC 400mg/q4w Melanoma 400mg/q4w TNBC 400mg/q4w NSCLC 300mg/q3w ATC 400 mg/q4w All Phase II Patients
Hide Arm/Group Description Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w Phase I Dose escalation cohort patients who took PRD001 10 mg/kg q2w Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w Phase I dose Cohorts - All patients in Phase I who took PDR001 q4w All patients in Phase I regardless of how they took PDR001 Phase II: non-small cell cancer patients who took PDR001 400 mg/q4w Phase II: Melanoma patients who took PDR001 400 mg/q4w Phase II: Triple negative breast cancer (TNBC) patients who took PDR001 400 mg/q4w Phase II: non-small cell cancer patients who took PDR001 300 mg/q3w Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w All patients in Phase II regardless of how they took PDR001
All-Cause Mortality
1mg/kg q2w 3mg/kg q2w 10mg/kg q2w All Phase I q2w 3mg/kg q4w 5mg/kg q4w All Phase I q4w All Phase I Patients NSCLC 400mg/q4w Melanoma 400mg/q4w TNBC 400mg/q4w NSCLC 300mg/q3w ATC 400 mg/q4w All Phase II Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/16 (12.50%)   2/15 (13.33%)   1/11 (9.09%)   5/42 (11.90%)   1/6 (16.67%)   2/10 (20.00%)   3/16 (18.75%)   8/58 (13.79%)   4/59 (6.78%)   4/61 (6.56%)   4/40 (10.00%)   12/59 (20.34%)   11/42 (26.19%)   35/261 (13.41%) 
Hide Serious Adverse Events
1mg/kg q2w 3mg/kg q2w 10mg/kg q2w All Phase I q2w 3mg/kg q4w 5mg/kg q4w All Phase I q4w All Phase I Patients NSCLC 400mg/q4w Melanoma 400mg/q4w TNBC 400mg/q4w NSCLC 300mg/q3w ATC 400 mg/q4w All Phase II Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/16 (56.25%)   7/15 (46.67%)   4/11 (36.36%)   20/42 (47.62%)   2/6 (33.33%)   2/10 (20.00%)   4/16 (25.00%)   24/58 (41.38%)   27/59 (45.76%)   22/61 (36.07%)   18/40 (45.00%)   37/59 (62.71%)   22/42 (52.38%)   126/261 (48.28%) 
Blood and lymphatic system disorders                             
Anaemia  1  2/16 (12.50%)  0/15 (0.00%)  0/11 (0.00%)  2/42 (4.76%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  2/58 (3.45%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  2/261 (0.77%) 
Lymphadenopathy  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Thrombocytopenia  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Cardiac disorders                             
Acute coronary syndrome  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Acute myocardial infarction  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Arrhythmia  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Atrial fibrillation  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  3/59 (5.08%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  4/261 (1.53%) 
Atrial flutter  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Cardiac arrest  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  2/59 (3.39%)  1/42 (2.38%)  3/261 (1.15%) 
Cardiac tamponade  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Coronary artery stenosis  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Myocardial infarction  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Pericardial effusion  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  2/59 (3.39%)  0/42 (0.00%)  3/261 (1.15%) 
Tachycardia  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  1/59 (1.69%)  0/42 (0.00%)  2/261 (0.77%) 
Endocrine disorders                             
Adrenal insufficiency  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Eye disorders                             
Diplopia  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Gastrointestinal disorders                             
Abdominal distension  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Abdominal pain  1  1/16 (6.25%)  2/15 (13.33%)  0/11 (0.00%)  3/42 (7.14%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  3/58 (5.17%)  0/59 (0.00%)  1/61 (1.64%)  2/40 (5.00%)  0/59 (0.00%)  0/42 (0.00%)  3/261 (1.15%) 
Autoimmune colitis  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Constipation  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Diarrhoea  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  2/59 (3.39%)  0/42 (0.00%)  2/261 (0.77%) 
Dysphagia  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  2/42 (4.76%)  3/261 (1.15%) 
Gastric ulcer  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Gastrointestinal haemorrhage  1  1/16 (6.25%)  1/15 (6.67%)  0/11 (0.00%)  2/42 (4.76%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  2/58 (3.45%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Ileus  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Intestinal obstruction  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  1/6 (16.67%)  0/10 (0.00%)  1/16 (6.25%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Melaena  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Nausea  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  2/58 (3.45%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Rectal haemorrhage  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Upper gastrointestinal haemorrhage  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Vomiting  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  1/58 (1.72%)  1/59 (1.69%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  2/261 (0.77%) 
General disorders                             
Asthenia  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Complication of device insertion  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Fatigue  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Non-cardiac chest pain  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Oedema peripheral  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  2/261 (0.77%) 
Pain  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Peripheral swelling  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Pyrexia  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  1/40 (2.50%)  2/59 (3.39%)  0/42 (0.00%)  4/261 (1.53%) 
Hepatobiliary disorders                             
Autoimmune hepatitis  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Bile duct obstruction  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Hepatic failure  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Hyperbilirubinaemia  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Jaundice  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Immune system disorders                             
Anaphylactic reaction  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Sarcoidosis  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Infections and infestations                             
Bacteraemia  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Bronchitis  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Cellulitis  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  2/61 (3.28%)  0/40 (0.00%)  0/59 (0.00%)  2/42 (4.76%)  4/261 (1.53%) 
Clostridium difficile infection  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Empyema  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Gastroenteritis viral  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Localised infection  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Pneumonia  1  1/16 (6.25%)  1/15 (6.67%)  0/11 (0.00%)  2/42 (4.76%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  2/58 (3.45%)  3/59 (5.08%)  0/61 (0.00%)  0/40 (0.00%)  5/59 (8.47%)  3/42 (7.14%)  11/261 (4.21%) 
Postoperative wound infection  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Respiratory tract infection  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  2/261 (0.77%) 
Sepsis  1  1/16 (6.25%)  1/15 (6.67%)  0/11 (0.00%)  2/42 (4.76%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  2/58 (3.45%)  1/59 (1.69%)  0/61 (0.00%)  1/40 (2.50%)  1/59 (1.69%)  0/42 (0.00%)  3/261 (1.15%) 
Septic shock  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  2/261 (0.77%) 
Urinary tract infection  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  2/40 (5.00%)  0/59 (0.00%)  0/42 (0.00%)  2/261 (0.77%) 
Injury, poisoning and procedural complications                             
Hip fracture  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  2/261 (0.77%) 
Overdose  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Thoracic vertebral fracture  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Tracheal obstruction  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Wound dehiscence  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Investigations                             
Blood bilirubin increased  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Metabolism and nutrition disorders                             
Dehydration  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  2/58 (3.45%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  2/42 (4.76%)  3/261 (1.15%) 
Diabetic ketoacidosis  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Failure to thrive  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  1/58 (1.72%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Hypercalcaemia  1  1/16 (6.25%)  1/15 (6.67%)  0/11 (0.00%)  2/42 (4.76%)  1/6 (16.67%)  0/10 (0.00%)  1/16 (6.25%)  3/58 (5.17%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  1/42 (2.38%)  3/261 (1.15%) 
Hyperkalaemia  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  2/58 (3.45%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Hypoglycaemia  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Hypokalaemia  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  2/261 (0.77%) 
Hyponatraemia  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  2/58 (3.45%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Musculoskeletal and connective tissue disorders                             
Back pain  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  1/40 (2.50%)  4/59 (6.78%)  0/42 (0.00%)  6/261 (2.30%) 
Bone pain  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Fistula  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Groin pain  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Musculoskeletal chest pain  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  2/261 (0.77%) 
Pain in extremity  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Sjogren's syndrome  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                             
Bladder cancer  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Cancer pain  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Intracranial tumour haemorrhage  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  2/261 (0.77%) 
Metastases to central nervous system  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  2/261 (0.77%) 
Second primary malignancy  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Tumour haemorrhage  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  2/61 (3.28%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  2/261 (0.77%) 
Tumour inflammation  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Tumour pain  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  2/40 (5.00%)  0/59 (0.00%)  0/42 (0.00%)  3/261 (1.15%) 
Nervous system disorders                             
Ataxia  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Carotid artery occlusion  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Central nervous system lesion  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Cognitive disorder  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Encephalopathy  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Facial paralysis  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Haemorrhage intracranial  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Hydrocephalus  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Intracranial pressure increased  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Ischaemic stroke  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Seizure  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  2/261 (0.77%) 
Spinal cord compression  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  3/59 (5.08%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  3/261 (1.15%) 
Psychiatric disorders                             
Confusional state  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Depression  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Mental status changes  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  1/6 (16.67%)  0/10 (0.00%)  1/16 (6.25%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Renal and urinary disorders                             
Renal failure  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Reproductive system and breast disorders                             
Pelvic pain  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Respiratory, thoracic and mediastinal disorders                             
Acute respiratory distress syndrome  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Bronchial obstruction  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Chronic obstructive pulmonary disease  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Cough  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
Dyspnoea  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  2/58 (3.45%)  3/59 (5.08%)  1/61 (1.64%)  3/40 (7.50%)  7/59 (11.86%)  2/42 (4.76%)  16/261 (6.13%) 
Haemoptysis  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  2/59 (3.39%)  0/42 (0.00%)  2/261 (0.77%) 
Hypoxia  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Obstructive airways disorder  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Pharyngeal haemorrhage  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Pleural effusion  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  2/58 (3.45%)  1/59 (1.69%)  1/61 (1.64%)  5/40 (12.50%)  2/59 (3.39%)  2/42 (4.76%)  11/261 (4.21%) 
Pneumonia aspiration  1  1/16 (6.25%)  1/15 (6.67%)  0/11 (0.00%)  2/42 (4.76%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  2/58 (3.45%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Pneumonitis  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  2/59 (3.39%)  1/61 (1.64%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  4/261 (1.53%) 
Pneumothorax  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Pulmonary embolism  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Respiratory distress  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Respiratory failure  1  0/16 (0.00%)  1/15 (6.67%)  1/11 (9.09%)  2/42 (4.76%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  2/58 (3.45%)  2/59 (3.39%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  3/261 (1.15%) 
Tracheal stenosis  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Skin and subcutaneous tissue disorders                             
Dermatitis atopic  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Vascular disorders                             
Embolism  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  1/59 (1.69%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  3/261 (1.15%) 
Hypotension  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Lymphoedema  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Lymphorrhoea  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Superior vena cava syndrome  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  0/42 (0.00%)  1/261 (0.38%) 
1
Term from vocabulary, MedDRA (23.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
1mg/kg q2w 3mg/kg q2w 10mg/kg q2w All Phase I q2w 3mg/kg q4w 5mg/kg q4w All Phase I q4w All Phase I Patients NSCLC 400mg/q4w Melanoma 400mg/q4w TNBC 400mg/q4w NSCLC 300mg/q3w ATC 400 mg/q4w All Phase II Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   16/16 (100.00%)   15/15 (100.00%)   11/11 (100.00%)   42/42 (100.00%)   6/6 (100.00%)   10/10 (100.00%)   16/16 (100.00%)   58/58 (100.00%)   54/59 (91.53%)   55/61 (90.16%)   37/40 (92.50%)   56/59 (94.92%)   39/42 (92.86%)   241/261 (92.34%) 
Blood and lymphatic system disorders                             
Anaemia  1  5/16 (31.25%)  7/15 (46.67%)  2/11 (18.18%)  14/42 (33.33%)  1/6 (16.67%)  3/10 (30.00%)  4/16 (25.00%)  18/58 (31.03%)  16/59 (27.12%)  13/61 (21.31%)  6/40 (15.00%)  8/59 (13.56%)  11/42 (26.19%)  54/261 (20.69%) 
Disseminated intravascular coagulation  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Eosinophilia  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  1/6 (16.67%)  0/10 (0.00%)  1/16 (6.25%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Iron deficiency anaemia  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Leukocytosis  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Leukopenia  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  2/61 (3.28%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  2/261 (0.77%) 
Lymph node pain  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Lymphopenia  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  1/59 (1.69%)  3/61 (4.92%)  1/40 (2.50%)  1/59 (1.69%)  1/42 (2.38%)  7/261 (2.68%) 
Neutropenia  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  1/59 (1.69%)  1/42 (2.38%)  2/261 (0.77%) 
Thrombocytopenia  1  0/16 (0.00%)  2/15 (13.33%)  0/11 (0.00%)  2/42 (4.76%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  2/58 (3.45%)  0/59 (0.00%)  2/61 (3.28%)  1/40 (2.50%)  2/59 (3.39%)  1/42 (2.38%)  6/261 (2.30%) 
Cardiac disorders                             
Palpitations  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Sinus tachycardia  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  1/59 (1.69%)  1/61 (1.64%)  1/40 (2.50%)  2/59 (3.39%)  1/42 (2.38%)  6/261 (2.30%) 
Tachycardia  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  2/58 (3.45%)  1/59 (1.69%)  2/61 (3.28%)  0/40 (0.00%)  1/59 (1.69%)  1/42 (2.38%)  5/261 (1.92%) 
Ear and labyrinth disorders                             
Hypoacusis  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Otorrhoea  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Vertigo  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  1/59 (1.69%)  1/42 (2.38%)  3/261 (1.15%) 
Endocrine disorders                             
Hyperthyroidism  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  0/58 (0.00%)  5/59 (8.47%)  4/61 (6.56%)  1/40 (2.50%)  2/59 (3.39%)  1/42 (2.38%)  13/261 (4.98%) 
Hypothyroidism  1  3/16 (18.75%)  3/15 (20.00%)  1/11 (9.09%)  7/42 (16.67%)  0/6 (0.00%)  2/10 (20.00%)  2/16 (12.50%)  9/58 (15.52%)  4/59 (6.78%)  5/61 (8.20%)  3/40 (7.50%)  3/59 (5.08%)  2/42 (4.76%)  17/261 (6.51%) 
Eye disorders                             
Periorbital oedema  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Photopsia  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Vision blurred  1  1/16 (6.25%)  1/15 (6.67%)  0/11 (0.00%)  2/42 (4.76%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  2/58 (3.45%)  0/59 (0.00%)  0/61 (0.00%)  1/40 (2.50%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Gastrointestinal disorders                             
Abdominal discomfort  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Abdominal distension  1  1/16 (6.25%)  1/15 (6.67%)  1/11 (9.09%)  3/42 (7.14%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  4/58 (6.90%)  1/59 (1.69%)  1/61 (1.64%)  1/40 (2.50%)  0/59 (0.00%)  1/42 (2.38%)  4/261 (1.53%) 
Abdominal pain  1  3/16 (18.75%)  2/15 (13.33%)  2/11 (18.18%)  7/42 (16.67%)  2/6 (33.33%)  3/10 (30.00%)  5/16 (31.25%)  12/58 (20.69%)  3/59 (5.08%)  2/61 (3.28%)  5/40 (12.50%)  5/59 (8.47%)  3/42 (7.14%)  18/261 (6.90%) 
Abdominal pain lower  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Abdominal pain upper  1  1/16 (6.25%)  1/15 (6.67%)  1/11 (9.09%)  3/42 (7.14%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  3/58 (5.17%)  1/59 (1.69%)  1/61 (1.64%)  0/40 (0.00%)  2/59 (3.39%)  0/42 (0.00%)  4/261 (1.53%) 
Ascites  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  2/6 (33.33%)  2/10 (20.00%)  4/16 (25.00%)  5/58 (8.62%)  0/59 (0.00%)  0/61 (0.00%)  2/40 (5.00%)  0/59 (0.00%)  0/42 (0.00%)  2/261 (0.77%) 
Autoimmune colitis  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Constipation  1  5/16 (31.25%)  5/15 (33.33%)  0/11 (0.00%)  10/42 (23.81%)  2/6 (33.33%)  0/10 (0.00%)  2/16 (12.50%)  12/58 (20.69%)  8/59 (13.56%)  7/61 (11.48%)  9/40 (22.50%)  9/59 (15.25%)  5/42 (11.90%)  38/261 (14.56%) 
Diarrhoea  1  7/16 (43.75%)  6/15 (40.00%)  1/11 (9.09%)  14/42 (33.33%)  0/6 (0.00%)  3/10 (30.00%)  3/16 (18.75%)  17/58 (29.31%)  8/59 (13.56%)  8/61 (13.11%)  1/40 (2.50%)  12/59 (20.34%)  8/42 (19.05%)  37/261 (14.18%) 
Dry mouth  1  3/16 (18.75%)  1/15 (6.67%)  1/11 (9.09%)  5/42 (11.90%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  6/58 (10.34%)  3/59 (5.08%)  3/61 (4.92%)  1/40 (2.50%)  0/59 (0.00%)  3/42 (7.14%)  10/261 (3.83%) 
Dyspepsia  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  2/58 (3.45%)  2/59 (3.39%)  3/61 (4.92%)  0/40 (0.00%)  1/59 (1.69%)  1/42 (2.38%)  7/261 (2.68%) 
Dysphagia  1  1/16 (6.25%)  2/15 (13.33%)  0/11 (0.00%)  3/42 (7.14%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  3/58 (5.17%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  3/59 (5.08%)  5/42 (11.90%)  8/261 (3.07%) 
Flatulence  1  0/16 (0.00%)  1/15 (6.67%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Gastrooesophageal reflux disease  1  2/16 (12.50%)  1/15 (6.67%)  0/11 (0.00%)  3/42 (7.14%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  3/58 (5.17%)  1/59 (1.69%)  1/61 (1.64%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  2/261 (0.77%) 
Mouth haemorrhage  1  0/16 (0.00%)  0/15 (0.00%)  1/11 (9.09%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  1/42 (2.38%)  1/261 (0.38%) 
Mouth ulceration  1  0/16 (0.00%)  0/15 (0.00%)  0/11 (0.00%)  0/42 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  1/16 (6.25%)  1/58 (1.72%)  1/59 (1.69%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  1/261 (0.38%) 
Nausea  1  7/16 (43.75%)  4/15 (26.67%)  3/11 (27.27%)  14/42 (33.33%)  3/6 (50.00%)  4/10 (40.00%)  7/16 (43.75%)  21/58 (36.21%)  9/59 (15.25%)  6/61 (9.84%)  13/40 (32.50%)  15/59 (25.42%)  2/42 (4.76%)  45/261 (17.24%) 
Pancreatic duct dilatation  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Rectal haemorrhage  1  1/16 (6.25%)  0/15 (0.00%)  0/11 (0.00%)  1/42 (2.38%)  0/6 (0.00%)  0/10 (0.00%)  0/16 (0.00%)  1/58 (1.72%)  0/59 (0.00%)  0/61 (0.00%)  0/40 (0.00%)  0/59 (0.00%)  0/42 (0.00%)  0/261 (0.00%) 
Stomatitis  1