Trial Outcomes & Findings for A Study of AUY922 in Non-small-cell Lung Cancer Patients Who Have Received Previous Two Lines of Chemotherapy. (NCT NCT01124864)
NCT ID: NCT01124864
Last Updated: 2016-03-02
Results Overview
The primary endpoint of the study was the investigator assessment of efficacy at 18 weeks in terms of response complete response (CR)/partial response (PR), stable disease (SD), or non clinical benefit (NCB) as assessed by response evaluation criteriain solid tumors (RECIST) version 1.0. ORR = patients with confirmed complete or partial response. Stable disease at 18 weeks = patients without response and with no assessment of progressive disease up to 18 weeks, but with an assessment of stable disease or better either within 2 weeks prior to the 18 week time point, or at the next non-missing assessment after the 18 week time point. No clinical benefit = all other patients.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
153 participants
Primary outcome timeframe
18 weeks
Results posted on
2016-03-02
Participant Flow
Two patients who were ongoing at the data cut-off of 30-Jul-2013 are considered as 'completed' in this study.
Participant milestones
| Measure |
Kras Mutant Patients
Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR Mutant Patients
Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR and Kras Wild Type Patients
Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Patients With EML4-ALK Translocation
Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Modified EGFR Mutant Patients
The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
For some patients, it was not possible to determine their genotype, and hence their stratum membership could not be determined. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
28
|
35
|
34
|
22
|
31
|
3
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
1
|
1
|
0
|
|
Overall Study
NOT COMPLETED
|
28
|
35
|
34
|
21
|
30
|
3
|
Reasons for withdrawal
| Measure |
Kras Mutant Patients
Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR Mutant Patients
Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR and Kras Wild Type Patients
Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Patients With EML4-ALK Translocation
Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Modified EGFR Mutant Patients
The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
For some patients, it was not possible to determine their genotype, and hence their stratum membership could not be determined. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
|---|---|---|---|---|---|---|
|
Overall Study
Follow up phase competed as per protocol
|
18
|
22
|
24
|
18
|
26
|
2
|
|
Overall Study
Death
|
6
|
9
|
6
|
2
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
3
|
4
|
0
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
0
|
1
|
0
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
A Study of AUY922 in Non-small-cell Lung Cancer Patients Who Have Received Previous Two Lines of Chemotherapy.
Baseline characteristics by cohort
| Measure |
Kras Mutant Patients
n=28 Participants
Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR Mutant Patients
n=35 Participants
Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR and Kras Wild Type Patients
n=34 Participants
Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Patients With EML4-ALK Translocation
n=22 Participants
Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Modified EGFR Mutant Patients
n=31 Participants
The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Unknown
n=3 Participants
For some patients, it was not possible to determine their genotype, and hence their stratum membership could not be determined. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Total
n=153 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Customized
< 65 years
|
20 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
25 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
108 Participants
n=8 Participants
|
|
Age, Customized
>= 65 years
|
8 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
45 Participants
n=8 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
88 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
65 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
25 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
107 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Black
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
41 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
|
Height
|
170.5 cm
STANDARD_DEVIATION 9.94 • n=5 Participants
|
163.0 cm
STANDARD_DEVIATION 6.63 • n=7 Participants
|
165.8 cm
STANDARD_DEVIATION 10.32 • n=5 Participants
|
164.9 cm
STANDARD_DEVIATION 9.80 • n=4 Participants
|
163.9 cm
STANDARD_DEVIATION 8.93 • n=21 Participants
|
173.0 cm
STANDARD_DEVIATION 14.73 • n=8 Participants
|
165.7 cm
STANDARD_DEVIATION 9.49 • n=8 Participants
|
|
Weight
|
74.5 kg
STANDARD_DEVIATION 16.22 • n=5 Participants
|
64.0 kg
STANDARD_DEVIATION 12.05 • n=7 Participants
|
68.4 kg
STANDARD_DEVIATION 13.49 • n=5 Participants
|
60.5 kg
STANDARD_DEVIATION 12.30 • n=4 Participants
|
67.1 kg
STANDARD_DEVIATION 11.02 • n=21 Participants
|
76.6 kg
STANDARD_DEVIATION 15.75 • n=8 Participants
|
67.3 kg
STANDARD_DEVIATION 13.70 • n=8 Participants
|
|
Weight category
< 55 kg
|
4 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
32 Participants
n=8 Participants
|
|
Weight category
55 - <75 kg
|
13 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
84 Participants
n=8 Participants
|
|
Weight category
>= 75 kg
|
11 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
37 Participants
n=8 Participants
|
|
Body surface area
|
1.9 m^2
STANDARD_DEVIATION 0.23 • n=5 Participants
|
1.7 m^2
STANDARD_DEVIATION 0.18 • n=7 Participants
|
1.8 m^2
STANDARD_DEVIATION 0.21 • n=5 Participants
|
1.7 m^2
STANDARD_DEVIATION 0.20 • n=4 Participants
|
1.8 m^2
STANDARD_DEVIATION 0.18 • n=21 Participants
|
1.9 m^2
STANDARD_DEVIATION 0.27 • n=8 Participants
|
1.8 m^2
STANDARD_DEVIATION 0.21 • n=8 Participants
|
|
Percentage of LVEF (left ventricular ejection fraction)
|
63.2 Percentage of LVEF
STANDARD_DEVIATION 8.92 • n=5 Participants
|
66.9 Percentage of LVEF
STANDARD_DEVIATION 7.63 • n=7 Participants
|
66.2 Percentage of LVEF
STANDARD_DEVIATION 9.27 • n=5 Participants
|
69.5 Percentage of LVEF
STANDARD_DEVIATION 8.68 • n=4 Participants
|
65.4 Percentage of LVEF
STANDARD_DEVIATION 7.64 • n=21 Participants
|
69.0 Percentage of LVEF
STANDARD_DEVIATION 10.54 • n=8 Participants
|
66.2 Percentage of LVEF
STANDARD_DEVIATION 8.51 • n=8 Participants
|
|
WHO Performance status
Who Performance status: 0
|
10 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
54 Participants
n=8 Participants
|
|
WHO Performance status
Who Performance status: 1
|
18 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
91 Participants
n=8 Participants
|
|
WHO Performance status
Who Performance status: 2
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
8 Participants
n=8 Participants
|
|
Smoking status
Current smoker
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
10 Participants
n=8 Participants
|
|
Smoking status
Ex-smoker
|
21 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
72 Participants
n=8 Participants
|
|
Smoking status
Never smoked
|
4 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
14 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
71 Participants
n=8 Participants
|
|
Time since smoking cessation
|
59.0 months
STANDARD_DEVIATION 80.65 • n=5 Participants
|
176.6 months
STANDARD_DEVIATION 15.04 • n=7 Participants
|
180.3 months
STANDARD_DEVIATION 120.88 • n=5 Participants
|
NA months
STANDARD_DEVIATION NA • n=4 Participants
|
340.4 months
STANDARD_DEVIATION 179.18 • n=21 Participants
|
NA months
STANDARD_DEVIATION NA • n=8 Participants
|
152.4 months
STANDARD_DEVIATION 142.22 • n=8 Participants
|
PRIMARY outcome
Timeframe: 18 weeksPopulation: The Full Analysis Set (FAS) consisted of all patients who received at least one dose of AUY922.
The primary endpoint of the study was the investigator assessment of efficacy at 18 weeks in terms of response complete response (CR)/partial response (PR), stable disease (SD), or non clinical benefit (NCB) as assessed by response evaluation criteriain solid tumors (RECIST) version 1.0. ORR = patients with confirmed complete or partial response. Stable disease at 18 weeks = patients without response and with no assessment of progressive disease up to 18 weeks, but with an assessment of stable disease or better either within 2 weeks prior to the 18 week time point, or at the next non-missing assessment after the 18 week time point. No clinical benefit = all other patients.
Outcome measures
| Measure |
Kras Mutant Patients
n=28 Participants
Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR Mutant Patients
n=35 Participants
Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR and Kras Wild Type Patients
n=34 Participants
Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Patients With EML4-ALK Translocation
n=22 Participants
Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Modified EGFR Mutant Patients
n=31 Participants
The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Unknown
n=3 Participants
For some patients, it was not possible to determine their genotype, and hence their stratum membership could not be determined. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
|---|---|---|---|---|---|---|
|
Response Assessment by Study Stratum - Per Investigator Assessment
Overall respose rate (ORR)
|
0 Participants
|
6 Participants
|
3 Participants
|
7 Participants
|
3 Participants
|
1 Participants
|
|
Response Assessment by Study Stratum - Per Investigator Assessment
Stable disease for ≥18 weeks
|
2 Participants
|
3 Participants
|
3 Participants
|
2 Participants
|
7 Participants
|
0 Participants
|
|
Response Assessment by Study Stratum - Per Investigator Assessment
No clinical benefit
|
26 Participants
|
26 Participants
|
28 Participants
|
13 Participants
|
21 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Week 12, Week 18Population: The Full Analysis Set (FAS) consisted of all patients who received at least one dose of AUY922.
Overall survival (OS) is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival was censored at the date of last contact.
Outcome measures
| Measure |
Kras Mutant Patients
n=28 Participants
Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR Mutant Patients
n=35 Participants
Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR and Kras Wild Type Patients
n=34 Participants
Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Patients With EML4-ALK Translocation
n=22 Participants
Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Modified EGFR Mutant Patients
n=31 Participants
The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Unknown
n=3 Participants
For some patients, it was not possible to determine their genotype, and hence their stratum membership could not be determined. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
|---|---|---|---|---|---|---|
|
Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review
12 weeks
|
68.7 Percentage of participants
Interval 47.0 to 83.0
|
77.0 Percentage of participants
Interval 59.3 to 8708.0
|
78.6 Percentage of participants
Interval 60.2 to 89.2
|
90.7 Percentage of participants
Interval 67.6 to 97.6
|
96.7 Percentage of participants
Interval 78.6 to 99.5
|
66.7 Percentage of participants
Interval 5.4 to 94.5
|
|
Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review
18 weeks
|
55.9 Percentage of participants
Interval 34.4 to 72.8
|
74.1 Percentage of participants
Interval 56.1 to 85.6
|
72.3 Percentage of participants
Interval 53.5 to 84.5
|
71.6 Percentage of participants
Interval 47.4 to 86.1
|
93.3 Percentage of participants
Interval 75.9 to 98.3
|
33.3 Percentage of participants
Interval 0.9 to 77.4
|
SECONDARY outcome
Timeframe: Week 12, Week 18Population: The Full Analysis Set (FAS) consisted of all patients who received at least one dose of AUY922.
Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient did not have an event, progression-free survival was censored at the date of last adequate tumor assessment. A Novartis modified response evaluation criteria in solid tumors RECIST 1.1 criteria was applied to CT/MRI imaging data when assessing any responses to AUY922 treatment. All images were evaluated locally by the investigator. All complete or partial responses were confirmed by a second assessment at least 4 weeks later.
Outcome measures
| Measure |
Kras Mutant Patients
n=28 Participants
Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR Mutant Patients
n=35 Participants
Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR and Kras Wild Type Patients
n=34 Participants
Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Patients With EML4-ALK Translocation
n=22 Participants
Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Modified EGFR Mutant Patients
n=31 Participants
The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Unknown
n=3 Participants
For some patients, it was not possible to determine their genotype, and hence their stratum membership could not be determined. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
|---|---|---|---|---|---|---|
|
Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review
12 weeks
|
31.5 Percentage of participants
Interval 14.9 to 49.6
|
44.4 Percentage of participants
Interval 27.0 to 60.5
|
31.5 Percentage of participants
Interval 16.3 to 47.9
|
45.5 Percentage of participants
Interval 24.4 to 64.3
|
56.4 Percentage of participants
Interval 36.9 to 72.0
|
33.3 Percentage of participants
Interval 0.9 to 77.4
|
|
Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review
18 weeks
|
9.0 Percentage of participants
Interval 1.6 to 24.6
|
27.7 Percentage of participants
Interval 13.5 to 43.9
|
24.0 Percentage of participants
Interval 10.6 to 40.3
|
36.4 Percentage of participants
Interval 17.4 to 55.7
|
37.8 Percentage of participants
Interval 20.4 to 55.1
|
33.3 Percentage of participants
Interval 0.9 to 77.4
|
SECONDARY outcome
Timeframe: 1 hour after infusionPopulation: PK analysis subset - All patients who received at least one dose of AUY922 in Cycle 1 and had at least one measurable post-dose AUY922 concentration.
Summary of PK parameters for all patients one hour post 70 mg/m2 AUY922 infusion for area under the curve infinity. There are discrepancies between sample numbers and study population because PK samples were not collected from all study subjects and thus were not analyzed.
Outcome measures
| Measure |
Kras Mutant Patients
n=119 Participants
Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR Mutant Patients
n=117 Participants
Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR and Kras Wild Type Patients
Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Patients With EML4-ALK Translocation
Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Modified EGFR Mutant Patients
The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Unknown
For some patients, it was not possible to determine their genotype, and hence their stratum membership could not be determined. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
|---|---|---|---|---|---|---|
|
Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUCinf
|
2101.27 h*ng/mL
Standard Deviation 990.320
|
13963.07 h*ng/mL
Standard Deviation 13006.537
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 hour after infusionPopulation: PK analysis subset - All patients who received at least one dose of AUY922 in Cycle 1 and had at least one measurable post-dose AUY922 concentration.
Summary of PK parameters for all patients one hour post 70 mg/m2 AUY922 infusion for area under the curve last. There are discrepancies between sample numbers and study population because PK samples were not collected from all study subjects and thus were not analyzed.
Outcome measures
| Measure |
Kras Mutant Patients
n=139 Participants
Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR Mutant Patients
n=142 Participants
Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR and Kras Wild Type Patients
Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Patients With EML4-ALK Translocation
Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Modified EGFR Mutant Patients
The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Unknown
For some patients, it was not possible to determine their genotype, and hence their stratum membership could not be determined. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
|---|---|---|---|---|---|---|
|
Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUClast
|
1997.04 h*ng/mL
Standard Deviation 894.903
|
12496.75 h*ng/mL
Standard Deviation 12035.525
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 hour after infusionPopulation: PK analysis subset - All patients who received at least one dose of AUY922 in Cycle 1 and had at least one measurable post-dose AUY922 concentration.
Summary of PK parameters for all patients one hour post 70 mg/m2 AUY922 infusion for concentration max. There are discrepancies between sample numbers and study population because PK samples were not collected from all study subjects and thus were not analyzed.
Outcome measures
| Measure |
Kras Mutant Patients
n=144 Participants
Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR Mutant Patients
n=144 Participants
Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR and Kras Wild Type Patients
Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Patients With EML4-ALK Translocation
Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Modified EGFR Mutant Patients
The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Unknown
For some patients, it was not possible to determine their genotype, and hence their stratum membership could not be determined. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
|---|---|---|---|---|---|---|
|
Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: Cmax
|
1130.59 ng/mL
Standard Deviation 705.177
|
2332.86 ng/mL
Standard Deviation 1377.350
|
—
|
—
|
—
|
—
|
Adverse Events
KRAS Mutant
Serious events: 17 serious events
Other events: 28 other events
Deaths: 0 deaths
EGFR Mutant
Serious events: 18 serious events
Other events: 35 other events
Deaths: 0 deaths
KRAS and EGFR Wild Type
Serious events: 22 serious events
Other events: 33 other events
Deaths: 0 deaths
EML4-ALK Translocation
Serious events: 6 serious events
Other events: 22 other events
Deaths: 0 deaths
Modified EGFR Mutant
Serious events: 11 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
KRAS Mutant
n=28 participants at risk
Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR Mutant
n=35 participants at risk
Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
KRAS and EGFR Wild Type
n=34 participants at risk
Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EML4-ALK Translocation
n=22 participants at risk
Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Modified EGFR Mutant
n=31 participants at risk
The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI.Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
n=3 participants at risk
For some patients, it was not possible to determine their genotype, and hence their stratum membership could not be determined. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
|---|---|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases To Central Nervous System
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic Pain
|
0.00%
0/28
|
2.9%
1/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/28
|
2.9%
1/35
|
2.9%
1/34
|
0.00%
0/22
|
12.9%
4/31
|
0.00%
0/3
|
|
Nervous system disorders
Balance Disorder
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Nervous system disorders
Brain Compression
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
3.6%
1/28
|
8.6%
3/35
|
2.9%
1/34
|
4.5%
1/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Nervous system disorders
Nervous System Disorder
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.00%
0/28
|
5.7%
2/35
|
0.00%
0/34
|
4.5%
1/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Nervous system disorders
Spinal Cord Compression
|
0.00%
0/28
|
2.9%
1/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Nervous system disorders
Vocal Cord Paresis
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Psychiatric disorders
Confusional State
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Psychiatric disorders
Depression
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
4.5%
1/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Anaemia
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Cardiac disorders
Atrial Fibrillation
|
0.00%
0/28
|
2.9%
1/35
|
5.9%
2/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Cardiac disorders
Bundle Branch Block Right
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Cardiac disorders
Cardio-Respiratory Arrest
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Cardiac disorders
Palpitations
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Cardiac disorders
Pericardial Effusion
|
0.00%
0/28
|
2.9%
1/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Cardiac disorders
Supraventricular Tachycardia
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/28
|
2.9%
1/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Eye disorders
Night Blindness
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Gastrointestinal disorders
Abdominal Distension
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
33.3%
1/3
|
|
Gastrointestinal disorders
Diarrhoea
|
3.6%
1/28
|
8.6%
3/35
|
2.9%
1/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Gastrointestinal disorders
Proctalgia
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Gastrointestinal disorders
Rectal Fissure
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.7%
3/28
|
5.7%
2/35
|
5.9%
2/34
|
13.6%
3/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Gastrointestinal disorders
Vomiting
|
3.6%
1/28
|
2.9%
1/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
General disorders
Asthenia
|
0.00%
0/28
|
2.9%
1/35
|
5.9%
2/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
General disorders
Fatigue
|
0.00%
0/28
|
0.00%
0/35
|
5.9%
2/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
General disorders
General Physical Health Deterioration
|
3.6%
1/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
General disorders
Mucosal Inflammation
|
0.00%
0/28
|
2.9%
1/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
General disorders
Oedema Peripheral
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
General disorders
Pain
|
3.6%
1/28
|
5.7%
2/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
General disorders
Pyrexia
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/28
|
2.9%
1/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Infections and infestations
Atypical Pneumonia
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
4.5%
1/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Infections and infestations
Bronchitis
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Infections and infestations
Klebsiella Infection
|
0.00%
0/28
|
2.9%
1/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Infections and infestations
Lung Infection
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
4.5%
1/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Infections and infestations
Perirectal Abscess
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Infections and infestations
Pneumonia
|
10.7%
3/28
|
2.9%
1/35
|
2.9%
1/34
|
4.5%
1/22
|
0.00%
0/31
|
33.3%
1/3
|
|
Infections and infestations
Respiratory Tract Infection
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
4.5%
1/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Dehydration
|
3.6%
1/28
|
2.9%
1/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Failure To Thrive
|
3.6%
1/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Fluid Intake Reduced
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
4.5%
1/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
3.6%
1/28
|
2.9%
1/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Vascular disorders
Hypertension
|
0.00%
0/28
|
5.7%
2/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Vascular disorders
Thrombosis
|
3.6%
1/28
|
2.9%
1/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
Other adverse events
| Measure |
KRAS Mutant
n=28 participants at risk
Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EGFR Mutant
n=35 participants at risk
Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
KRAS and EGFR Wild Type
n=34 participants at risk
Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
EML4-ALK Translocation
n=22 participants at risk
Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
Modified EGFR Mutant
n=31 participants at risk
The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI.Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
n=3 participants at risk
For some patients, it was not possible to determine their genotype, and hence their stratum membership could not be determined. Patients received AUY922 at 70 mg/m\^2 weekly infusions.
|
|---|---|---|---|---|---|---|
|
Nervous system disorders
Headache
|
28.6%
8/28
|
22.9%
8/35
|
23.5%
8/34
|
63.6%
14/22
|
41.9%
13/31
|
66.7%
2/3
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/28
|
0.00%
0/35
|
5.9%
2/34
|
9.1%
2/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Nervous system disorders
Memory Impairment
|
7.1%
2/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/28
|
8.6%
3/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Nervous system disorders
Neuropathy Peripheral
|
0.00%
0/28
|
0.00%
0/35
|
5.9%
2/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/28
|
0.00%
0/35
|
5.9%
2/34
|
13.6%
3/22
|
9.7%
3/31
|
0.00%
0/3
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
0.00%
0/28
|
0.00%
0/35
|
5.9%
2/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Nervous system disorders
Somnolence
|
3.6%
1/28
|
2.9%
1/35
|
5.9%
2/34
|
9.1%
2/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Psychiatric disorders
Anxiety
|
7.1%
2/28
|
5.7%
2/35
|
8.8%
3/34
|
9.1%
2/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Psychiatric disorders
Depressed Mood
|
0.00%
0/28
|
2.9%
1/35
|
5.9%
2/34
|
9.1%
2/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Psychiatric disorders
Hallucination
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
9.1%
2/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/28
|
8.6%
3/35
|
17.6%
6/34
|
22.7%
5/22
|
12.9%
4/31
|
0.00%
0/3
|
|
Psychiatric disorders
Nervousness
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
9.1%
2/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Reproductive system and breast disorders
Pelvic Pain
|
0.00%
0/28
|
5.7%
2/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.9%
5/28
|
22.9%
8/35
|
26.5%
9/34
|
31.8%
7/22
|
25.8%
8/31
|
33.3%
1/3
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/28
|
2.9%
1/35
|
5.9%
2/34
|
4.5%
1/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
17.9%
5/28
|
31.4%
11/35
|
26.5%
9/34
|
9.1%
2/22
|
6.5%
2/31
|
33.3%
1/3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea Exertional
|
0.00%
0/28
|
5.7%
2/35
|
5.9%
2/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
33.3%
1/3
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
14.3%
4/28
|
8.6%
3/35
|
11.8%
4/34
|
4.5%
1/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/28
|
2.9%
1/35
|
2.9%
1/34
|
0.00%
0/22
|
9.7%
3/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/28
|
5.7%
2/35
|
8.8%
3/34
|
9.1%
2/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Productive Cough
|
3.6%
1/28
|
11.4%
4/35
|
20.6%
7/34
|
9.1%
2/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/28
|
5.7%
2/35
|
5.9%
2/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Anaemia
|
3.6%
1/28
|
8.6%
3/35
|
14.7%
5/34
|
13.6%
3/22
|
12.9%
4/31
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/28
|
0.00%
0/35
|
5.9%
2/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/28
|
5.7%
2/35
|
2.9%
1/34
|
4.5%
1/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Ear and labyrinth disorders
Ear Pain
|
0.00%
0/28
|
2.9%
1/35
|
5.9%
2/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/28
|
2.9%
1/35
|
5.9%
2/34
|
9.1%
2/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Eye disorders
Accommodation Disorder
|
3.6%
1/28
|
5.7%
2/35
|
5.9%
2/34
|
9.1%
2/22
|
16.1%
5/31
|
0.00%
0/3
|
|
Eye disorders
Blepharitis
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Eye disorders
Cataract Subcapsular
|
3.6%
1/28
|
0.00%
0/35
|
5.9%
2/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Eye disorders
Colour Blindness Acquired
|
0.00%
0/28
|
8.6%
3/35
|
5.9%
2/34
|
22.7%
5/22
|
12.9%
4/31
|
33.3%
1/3
|
|
Eye disorders
Dry Eye
|
7.1%
2/28
|
0.00%
0/35
|
2.9%
1/34
|
9.1%
2/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Eye disorders
Eye Pain
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Eye disorders
Lacrimation Increased
|
0.00%
0/28
|
5.7%
2/35
|
0.00%
0/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Eye disorders
Loss Of Visual Contrast Sensitivity
|
0.00%
0/28
|
0.00%
0/35
|
5.9%
2/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Eye disorders
Night Blindness
|
10.7%
3/28
|
28.6%
10/35
|
17.6%
6/34
|
22.7%
5/22
|
32.3%
10/31
|
33.3%
1/3
|
|
Eye disorders
Ocular Toxicity
|
14.3%
4/28
|
11.4%
4/35
|
2.9%
1/34
|
13.6%
3/22
|
9.7%
3/31
|
33.3%
1/3
|
|
Eye disorders
Photophobia
|
10.7%
3/28
|
5.7%
2/35
|
14.7%
5/34
|
0.00%
0/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Eye disorders
Photopsia
|
10.7%
3/28
|
14.3%
5/35
|
29.4%
10/34
|
45.5%
10/22
|
19.4%
6/31
|
0.00%
0/3
|
|
Eye disorders
Retinal Disorder
|
3.6%
1/28
|
8.6%
3/35
|
2.9%
1/34
|
22.7%
5/22
|
22.6%
7/31
|
0.00%
0/3
|
|
Eye disorders
Vision Blurred
|
17.9%
5/28
|
17.1%
6/35
|
20.6%
7/34
|
27.3%
6/22
|
19.4%
6/31
|
0.00%
0/3
|
|
Eye disorders
Visual Acuity Reduced
|
3.6%
1/28
|
17.1%
6/35
|
20.6%
7/34
|
31.8%
7/22
|
16.1%
5/31
|
0.00%
0/3
|
|
Eye disorders
Visual Impairment
|
21.4%
6/28
|
22.9%
8/35
|
8.8%
3/34
|
27.3%
6/22
|
22.6%
7/31
|
0.00%
0/3
|
|
Eye disorders
Vitreous Floaters
|
3.6%
1/28
|
8.6%
3/35
|
2.9%
1/34
|
4.5%
1/22
|
6.5%
2/31
|
33.3%
1/3
|
|
Gastrointestinal disorders
Abdominal Distension
|
0.00%
0/28
|
0.00%
0/35
|
5.9%
2/34
|
9.1%
2/22
|
0.00%
0/31
|
33.3%
1/3
|
|
Gastrointestinal disorders
Abdominal Pain
|
17.9%
5/28
|
14.3%
5/35
|
11.8%
4/34
|
27.3%
6/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
3.6%
1/28
|
8.6%
3/35
|
5.9%
2/34
|
0.00%
0/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Gastrointestinal disorders
Constipation
|
21.4%
6/28
|
17.1%
6/35
|
14.7%
5/34
|
22.7%
5/22
|
16.1%
5/31
|
0.00%
0/3
|
|
Gastrointestinal disorders
Diarrhoea
|
89.3%
25/28
|
65.7%
23/35
|
73.5%
25/34
|
77.3%
17/22
|
77.4%
24/31
|
100.0%
3/3
|
|
Gastrointestinal disorders
Dry Mouth
|
17.9%
5/28
|
11.4%
4/35
|
17.6%
6/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/28
|
2.9%
1/35
|
2.9%
1/34
|
18.2%
4/22
|
9.7%
3/31
|
33.3%
1/3
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/28
|
5.7%
2/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Gastrointestinal disorders
Nausea
|
57.1%
16/28
|
54.3%
19/35
|
38.2%
13/34
|
50.0%
11/22
|
38.7%
12/31
|
33.3%
1/3
|
|
Gastrointestinal disorders
Oral Pain
|
0.00%
0/28
|
5.7%
2/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Gastrointestinal disorders
Rectal Haemorrhage
|
7.1%
2/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Gastrointestinal disorders
Stomatitis
|
3.6%
1/28
|
0.00%
0/35
|
5.9%
2/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Gastrointestinal disorders
Vomiting
|
46.4%
13/28
|
37.1%
13/35
|
11.8%
4/34
|
40.9%
9/22
|
12.9%
4/31
|
66.7%
2/3
|
|
General disorders
Asthenia
|
46.4%
13/28
|
40.0%
14/35
|
29.4%
10/34
|
45.5%
10/22
|
16.1%
5/31
|
33.3%
1/3
|
|
General disorders
Catheter Site Pain
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
6.5%
2/31
|
0.00%
0/3
|
|
General disorders
Chest Pain
|
3.6%
1/28
|
5.7%
2/35
|
0.00%
0/34
|
18.2%
4/22
|
0.00%
0/31
|
33.3%
1/3
|
|
General disorders
Fatigue
|
25.0%
7/28
|
25.7%
9/35
|
38.2%
13/34
|
13.6%
3/22
|
48.4%
15/31
|
0.00%
0/3
|
|
General disorders
Gait Disturbance
|
0.00%
0/28
|
5.7%
2/35
|
5.9%
2/34
|
9.1%
2/22
|
0.00%
0/31
|
0.00%
0/3
|
|
General disorders
Non-Cardiac Chest Pain
|
3.6%
1/28
|
0.00%
0/35
|
5.9%
2/34
|
9.1%
2/22
|
3.2%
1/31
|
0.00%
0/3
|
|
General disorders
Oedema Peripheral
|
7.1%
2/28
|
5.7%
2/35
|
2.9%
1/34
|
13.6%
3/22
|
9.7%
3/31
|
0.00%
0/3
|
|
General disorders
Pain
|
3.6%
1/28
|
5.7%
2/35
|
17.6%
6/34
|
0.00%
0/22
|
3.2%
1/31
|
33.3%
1/3
|
|
General disorders
Pyrexia
|
17.9%
5/28
|
8.6%
3/35
|
11.8%
4/34
|
27.3%
6/22
|
12.9%
4/31
|
66.7%
2/3
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
9.1%
2/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Infections and infestations
Influenza
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
9.7%
3/31
|
0.00%
0/3
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
4.5%
1/22
|
12.9%
4/31
|
33.3%
1/3
|
|
Infections and infestations
Respiratory Tract Infection
|
0.00%
0/28
|
0.00%
0/35
|
5.9%
2/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/28
|
5.7%
2/35
|
2.9%
1/34
|
9.1%
2/22
|
12.9%
4/31
|
0.00%
0/3
|
|
Infections and infestations
Urinary Tract Infection
|
3.6%
1/28
|
5.7%
2/35
|
0.00%
0/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Investigations
Alanine Aminotransferase Increased
|
3.6%
1/28
|
5.7%
2/35
|
2.9%
1/34
|
4.5%
1/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Investigations
Aspartate Aminotransferase Increased
|
0.00%
0/28
|
2.9%
1/35
|
2.9%
1/34
|
9.1%
2/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Investigations
Blood Alkaline Phosphatase Increased
|
0.00%
0/28
|
11.4%
4/35
|
2.9%
1/34
|
4.5%
1/22
|
9.7%
3/31
|
0.00%
0/3
|
|
Investigations
Blood Creatinine Increased
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
4.5%
1/22
|
3.2%
1/31
|
33.3%
1/3
|
|
Investigations
C-Reactive Protein Increased
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
6.5%
2/31
|
33.3%
1/3
|
|
Investigations
Gamma-Glutamyltransferase Increased
|
0.00%
0/28
|
5.7%
2/35
|
2.9%
1/34
|
0.00%
0/22
|
9.7%
3/31
|
0.00%
0/3
|
|
Investigations
Heart Rate Increased
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
33.3%
1/3
|
|
Investigations
Hypophonesis
|
0.00%
0/28
|
0.00%
0/35
|
2.9%
1/34
|
9.1%
2/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Investigations
Transaminases Increased
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Investigations
Weight Decreased
|
14.3%
4/28
|
2.9%
1/35
|
8.8%
3/34
|
4.5%
1/22
|
12.9%
4/31
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
60.7%
17/28
|
42.9%
15/35
|
35.3%
12/34
|
36.4%
8/22
|
32.3%
10/31
|
33.3%
1/3
|
|
Metabolism and nutrition disorders
Dehydration
|
3.6%
1/28
|
2.9%
1/35
|
8.8%
3/34
|
4.5%
1/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
3.6%
1/28
|
0.00%
0/35
|
2.9%
1/34
|
0.00%
0/22
|
3.2%
1/31
|
33.3%
1/3
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
7.1%
2/28
|
5.7%
2/35
|
0.00%
0/34
|
9.1%
2/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
3.6%
1/28
|
5.7%
2/35
|
2.9%
1/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
7.1%
2/28
|
11.4%
4/35
|
0.00%
0/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.6%
1/28
|
11.4%
4/35
|
5.9%
2/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
28.6%
8/28
|
14.3%
5/35
|
23.5%
8/34
|
13.6%
3/22
|
22.6%
7/31
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
0.00%
0/28
|
5.7%
2/35
|
2.9%
1/34
|
4.5%
1/22
|
9.7%
3/31
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Flank Pain
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
12.9%
4/31
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
7.1%
2/28
|
2.9%
1/35
|
2.9%
1/34
|
13.6%
3/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
3.6%
1/28
|
5.7%
2/35
|
5.9%
2/34
|
4.5%
1/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
10.7%
3/28
|
5.7%
2/35
|
14.7%
5/34
|
4.5%
1/22
|
6.5%
2/31
|
33.3%
1/3
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/28
|
11.4%
4/35
|
11.8%
4/34
|
22.7%
5/22
|
19.4%
6/31
|
33.3%
1/3
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
7.1%
2/28
|
0.00%
0/35
|
11.8%
4/34
|
4.5%
1/22
|
6.5%
2/31
|
33.3%
1/3
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
7.1%
2/28
|
11.4%
4/35
|
11.8%
4/34
|
4.5%
1/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
33.3%
1/3
|
|
Nervous system disorders
Ataxia
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
33.3%
1/3
|
|
Nervous system disorders
Balance Disorder
|
3.6%
1/28
|
0.00%
0/35
|
0.00%
0/34
|
4.5%
1/22
|
9.7%
3/31
|
0.00%
0/3
|
|
Nervous system disorders
Dizziness
|
3.6%
1/28
|
5.7%
2/35
|
2.9%
1/34
|
4.5%
1/22
|
9.7%
3/31
|
33.3%
1/3
|
|
Nervous system disorders
Dysgeusia
|
7.1%
2/28
|
2.9%
1/35
|
2.9%
1/34
|
0.00%
0/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/28
|
5.7%
2/35
|
0.00%
0/34
|
4.5%
1/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Dermatitis Acneiform
|
0.00%
0/28
|
0.00%
0/35
|
0.00%
0/34
|
4.5%
1/22
|
6.5%
2/31
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
3.6%
1/28
|
8.6%
3/35
|
2.9%
1/34
|
0.00%
0/22
|
12.9%
4/31
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Pain Of Skin
|
0.00%
0/28
|
0.00%
0/35
|
5.9%
2/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.1%
2/28
|
2.9%
1/35
|
2.9%
1/34
|
4.5%
1/22
|
12.9%
4/31
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.1%
2/28
|
5.7%
2/35
|
0.00%
0/34
|
4.5%
1/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.00%
0/28
|
5.7%
2/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
|
Vascular disorders
Hot Flush
|
3.6%
1/28
|
0.00%
0/35
|
2.9%
1/34
|
9.1%
2/22
|
3.2%
1/31
|
0.00%
0/3
|
|
Vascular disorders
Hypertension
|
0.00%
0/28
|
11.4%
4/35
|
8.8%
3/34
|
13.6%
3/22
|
16.1%
5/31
|
0.00%
0/3
|
|
Vascular disorders
Hypotension
|
0.00%
0/28
|
5.7%
2/35
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/31
|
0.00%
0/3
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER