A Study of AUY922 in Non-small-cell Lung Cancer Patients Who Have Received Previous Two Lines of Chemotherapy.

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01124864
• Collaborator: (none)
• Enrollment: 153
• Locations: 22
• Arms: 5
• Duration (Months): 46
• Patients Per Site: 7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will assess the efficacy of AUY922, when administered weekly at 70 mg/m2, in adult patients with advanced Non-small-cell Lung Cancer (NSCLC), who have received at least two prior lines of chemotherapy. Patients will be retrospectively, and prospectively, stratified based on their molecular tumor etiology. The following strata was assigned: Patients with Epidermal growth factor receptor (EGFR) activating mutations, Patients with Kirstin Raus sarcoma virus (KRAS) activating mutations, Patients with EML4-ALK (anaplastic lymphoma kinase) translocations and patients that were both EGFR and Kras wild type.

Condition or Disease	Intervention/Treatment	Phase
Non-small-cell Lung Cancer	Drug: AUY922	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 153 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multi-center, Open-label Study of AUY922 Administered IV on a Once-weekly Schedule in Patients With Advanced Non-small-cell Lung Cancer Who Have Received at Least Two Lines of Prior Chemotherapy
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: AUY922; AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution. AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.
Experimental: Kras mutant patients Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m^2 weekly infusions.	Drug: AUY922; AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution. AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.
Experimental: 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.	Drug: AUY922; AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution. AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.
Experimental: 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.	Drug: AUY922; AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution. AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.
Experimental: 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.	Drug: AUY922; AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution. AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.

Outcome Measures

Primary Outcome Measures

1. Response Assessment by Study Stratum - Per Investigator Assessment [18 weeks]

   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.

Secondary Outcome Measures

1. Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review [Week 12, Week 18]

   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.

2. Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review [Week 12, Week 18]

   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.

3. Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUCinf [1 hour after infusion]

   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.

4. Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUClast [1 hour after infusion]

   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.

5. Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: Cmax [1 hour after infusion]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with histologically or cytologically confirmed advanced (stage IIIB or stage

1. NSCLC who have received at least two prior lines of treatment. Patients who, in the investigators opinion, are deemed unsuitable for the standard 2nd line chemotherapy will be eligible for protocol participation. One of the prior lines must have included a platinum agent. Prior treatment with a platinum agent is not a requirement for EGFR mutant patients and patients with EML4-ALK translocations

• Patients enrolled to the fifth stratum, modified EGFR mutant, must have documented prior response to EGFR TKI as defined by CR, PR or SD for 6 months or greater unless patient has de novo resistance to EGFR TKI (e.g. exon 20 insertions.)

• All patients must have at least one measurable lesion as defined by RECIST criteria. Previously irradiated lesions are not measurable unless the lesion is new or has demonstrated clear progression after radiation

• World Health Organization (WHO) performance status ≤ 2. For patients enrolled to the fifth stratum, modified EGFR mutant, World Health Organization (WHO) performance status ≤ 1

• Patients enrolled to the fifth stratum, modified EGFR mutant, must be willing and suitable to undergo fresh baseline biopsy prior to study treatment (unless patient had recent biopsy after EGFR TKI progression that concluded resistance to EGFR TKI.)

• Hematologic:

• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L.

• Hemoglobin (Hgb) ≥ 9 g/dl.

• Platelets (plt) ≥ 100 x 109/L.

Biochemistry:

• Total calcium (corrected for serum albumin) within normal limits or correctable with supplements.

• Magnesium within lower normal limits or correctable with supplements.

Adequate liver function defined as:

• AST/SGOT and ALT/SGPT ≤ 3.0 x Upper limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastasis are present.

• Serum bilirubin ≤ 1.5 x ULN.

• Serum albumin > 2.5 g/dL.

• Serum creatinine ≤ 1.5 x ULN or 24 hour clearance ≥ 50 mL/min.

Exclusion Criteria:

• Patients who have received more than four lines of prior treatment. Exception: Patients enrolled to the fifth stratum, modified EGFR mutant, must not have received more than two prior lines of therapy. Chemotherapy administered as adjuvant treatment more than six months prior to study enrollment is not considered a prior line of therapy for purposes of this study.

• Patients with a history of CNS metastasis. Note: Patients without clinical signs and symptoms of CNS involvement are not required to have MRI of the brain. Exception: Patients with treated brain metastases who are asymptomatic, who has discontinued corticosteroids, and who have been clinically stable for one month will be eligible for protocol participation. This exception is not valid for patients enrolled to the fifth stratum, modified EGFR mutant. These patients must not have CNS involvement.

• Prior anti-neoplastic treatment with any HSP90 or HDAC inhibitor compound.

• Patients must not have received:

• any systemic anti-cancer treatment or radiotherapy within 4 weeks prior to first dose of study treatment and should have recovered to baseline or less than Grade 1 from toxicities of such therapy prior to the first dose of study treatment

• 2 weeks for palliative radiotherapy to bones, 6 weeks for nitrosoureas and mitomycin

• 4 weeks for monoclonal antibodies

• and ≤5 half-life of the agent or active metabolites [if any] for continuous systemic anti-cancer treatment or investigational

• Patients who do not have either an archival tumor sample available or are unwilling to have a fresh tumor sample collected at baseline.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California at Los Angeles UCLA - Santa Monica	Los Angeles	California	United States	90095
2	Maryland Oncology Hematology, P.A. Dept. of Assoc. Onc/Hem	Rockville	Maryland	United States	20850
3	Dana Farber Cancer Institute DFCI	Boston	Massachusetts	United States	02215
4	St. Luke's Hospital and Health Network St Luke's	Bethlehem	Pennsylvania	United States
5	Novartis Investigative Site	Edmonton	Alberta	Canada	T6G 1Z2
6	Novartis Investigative Site	Montreal	Quebec	Canada	H3T 1E2
7	Novartis Investigative Site	Creteil		France	94000
8	Novartis Investigative Site	Marseille cedex 20		France	13915
9	Novartis Investigative Site	Villejuif Cedex		France	94805
10	Novartis Investigative Site	Berlin		Germany	13125
11	Novartis Investigative Site	Oldenburg		Germany	26121
12	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	05505
13	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	06351
14	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	110 744
15	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	137-701
16	Novartis Investigative Site	Amsterdam		Netherlands	1081 HV
17	Novartis Investigative Site	Groningen		Netherlands	9713 GZ
18	Novartis Investigative Site	Oslo		Norway	NO-0379
19	Novartis Investigative Site	Singapore		Singapore	119228
20	Novartis Investigative Site	Badalona	Catalunya	Spain	08916
21	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
22	Novartis Investigative Site	Izmir		Turkey	35040

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01124864
• Other Study ID Numbers: CAUY922A2206; 2010-020116-11
• First Posted: May 17, 2010
• Last Update Posted: Mar 2, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Novartis Pharmaceuticals: Non-small-cell lung cancer; HSP90; 2nd to 3rd line treatment
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Study Results

Participant Flow

Recruitment Details	Two patients who were ongoing at the data cut-off of 30-Jul-2013 are considered as 'completed' in this study.

Arm/Group Title	Kras Mutant Patients	EGFR Mutant Patients	EGFR and Kras Wild Type Patients	Patients With EML4-ALK Translocation	Modified EGFR Mutant Patients
Arm/Group Description	Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m^2 weekly infusions.	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.	Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m^2 weekly infusions.	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.	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.
Period Title: Overall Study
STARTED	28	35	34	22	31	3
COMPLETED	0	0	0	1	1	0
NOT COMPLETED	28	35	34	21	30	3

Baseline Characteristics

Arm/Group Title	Kras Mutant Patients	EGFR Mutant Patients	EGFR and Kras Wild Type Patients	Patients With EML4-ALK Translocation	Modified EGFR Mutant Patients	Unknown	Total
Arm/Group Description	Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m^2 weekly infusions.	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.	Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m^2 weekly infusions.	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.	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.	Total of all reporting groups
Overall Participants	28	35	34	22	31	3	153
Age, Customized (Number) [Number]
< 65 years	20 71.4%	21 60%	23 67.6%	18 81.8%	25 80.6%	1 33.3%	108 70.6%
>= 65 years	8 28.6%	14 40%	11 32.4%	4 18.2%	6 19.4%	2 66.7%	45 29.4%
Sex: Female, Male (Count of Participants)
Female	11 39.3%	25 71.4%	18 52.9%	15 68.2%	19 61.3%	0 0%	88 57.5%
Male	17 60.7%	10 28.6%	16 47.1%	7 31.8%	12 38.7%	3 100%	65 42.5%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	25 89.3%	25 71.4%	23 67.6%	16 72.7%	16 51.6%	2 66.7%	107 69.9%
Black	0 0%	0 0%	1 2.9%	0 0%	0 0%	0 0%	1 0.7%
Asian	2 7.1%	10 28.6%	9 26.5%	6 27.3%	13 41.9%	1 33.3%	41 26.8%
Other	1 3.6%	0 0%	1 2.9%	0 0%	2 6.5%	0 0%	4 2.6%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	170.5 (9.94)	163.0 (6.63)	165.8 (10.32)	164.9 (9.80)	163.9 (8.93)	173.0 (14.73)	165.7 (9.49)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	74.5 (16.22)	64.0 (12.05)	68.4 (13.49)	60.5 (12.30)	67.1 (11.02)	76.6 (15.75)	67.3 (13.70)
Weight category (Number) [Number]
< 55 kg	4 14.3%	10 28.6%	4 11.8%	10 45.5%	4 12.9%	0 0%	32 20.9%
55 - <75 kg	13 46.4%	19 54.3%	21 61.8%	9 40.9%	20 64.5%	2 66.7%	84 54.9%
>= 75 kg	11 39.3%	6 17.1%	9 26.5%	3 13.6%	7 22.6%	1 33.3%	37 24.2%
Body surface area (m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m^2]	1.9 (0.23)	1.7 (0.18)	1.8 (0.21)	1.7 (0.20)	1.8 (0.18)	1.9 (0.27)	1.8 (0.21)
Percentage of LVEF (left ventricular ejection fraction) (Percentage of LVEF) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of LVEF]	63.2 (8.92)	66.9 (7.63)	66.2 (9.27)	69.5 (8.68)	65.4 (7.64)	69.0 (10.54)	66.2 (8.51)
WHO Performance status (Number) [Number]
Who Performance status: 0	10 35.7%	13 37.1%	10 29.4%	9 40.9%	11 35.5%	1 33.3%	54 35.3%
Who Performance status: 1	18 64.3%	19 54.3%	21 61.8%	11 50%	20 64.5%	2 66.7%	91 59.5%
Who Performance status: 2	0 0%	3 8.6%	3 8.8%	2 9.1%	0 0%	0 0%	8 5.2%
Smoking status (Number) [Number]
Current smoker	3 10.7%	1 2.9%	2 5.9%	2 9.1%	1 3.2%	1 33.3%	10 6.5%
Ex-smoker	21 75%	12 34.3%	18 52.9%	5 22.7%	16 51.6%	0 0%	72 47.1%
Never smoked	4 14.3%	22 62.9%	14 41.2%	15 68.2%	14 45.2%	2 66.7%	71 46.4%
Time since smoking cessation (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	59.0 (80.65)	176.6 (15.04)	180.3 (120.88)	NA (NA)	340.4 (179.18)	NA (NA)	152.4 (142.22)

Outcome Measures

1. Primary Outcome

Title	Response Assessment by Study Stratum - Per Investigator Assessment
Description	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.
Time Frame	18 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who received at least one dose of AUY922.

Arm/Group Title	Kras Mutant Patients	EGFR Mutant Patients	EGFR and Kras Wild Type Patients	Patients With EML4-ALK Translocation	Modified EGFR Mutant Patients	Unknown
Arm/Group Description	Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m^2 weekly infusions.	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.	Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m^2 weekly infusions.	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.	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.
Measure Participants	28	35	34	22	31	3
Overall respose rate (ORR)	0 0%	6 17.1%	3 8.8%	7 31.8%	3 9.7%	1 33.3%
Stable disease for ≥18 weeks	2 7.1%	3 8.6%	3 8.8%	2 9.1%	7 22.6%	0 0%
No clinical benefit	26 92.9%	26 74.3%	28 82.4%	13 59.1%	21 67.7%	2 66.7%

2. Secondary Outcome

Title	Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review
Description	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.
Time Frame	Week 12, Week 18

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who received at least one dose of AUY922.

Arm/Group Title	Kras Mutant Patients	EGFR Mutant Patients	EGFR and Kras Wild Type Patients	Patients With EML4-ALK Translocation	Modified EGFR Mutant Patients	Unknown
Arm/Group Description	Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m^2 weekly infusions.	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.	Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m^2 weekly infusions.	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.	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.
Measure Participants	28	35	34	22	31	3
12 weeks	68.7 245.4%	77.0 220%	78.6 231.2%	90.7 412.3%	96.7 311.9%	66.7 2223.3%
18 weeks	55.9 199.6%	74.1 211.7%	72.3 212.6%	71.6 325.5%	93.3 301%	33.3 1110%

3. Secondary Outcome

Title	Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review
Description	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.
Time Frame	Week 12, Week 18

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients who received at least one dose of AUY922.

Arm/Group Title	Kras Mutant Patients	EGFR Mutant Patients	EGFR and Kras Wild Type Patients	Patients With EML4-ALK Translocation	Modified EGFR Mutant Patients	Unknown
Arm/Group Description	Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m^2 weekly infusions.	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.	Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m^2 weekly infusions.	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.	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.
Measure Participants	28	35	34	22	31	3
12 weeks	31.5 112.5%	44.4 126.9%	31.5 92.6%	45.5 206.8%	56.4 181.9%	33.3 1110%
18 weeks	9.0 32.1%	27.7 79.1%	24.0 70.6%	36.4 165.5%	37.8 121.9%	33.3 1110%

4. Secondary Outcome

Title	Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUCinf
Description	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.
Time Frame	1 hour after infusion

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AUY922	BJP762
Arm/Group Description	AUY922 Plasma Concentration	AUY Metabolite
Measure Participants	119	117
Mean (Standard Deviation) [h*ng/mL]	2101.27 (990.320)	13963.07 (13006.537)

5. Secondary Outcome

Title	Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUClast
Description	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.
Time Frame	1 hour after infusion

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AUY922	BJP762
Arm/Group Description	AUY922 Plasma Concentration	AUY Metabolite
Measure Participants	139	142
Mean (Standard Deviation) [h*ng/mL]	1997.04 (894.903)	12496.75 (12035.525)

6. Secondary Outcome

Title	Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: Cmax
Description	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.
Time Frame	1 hour after infusion

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AUY922	BJP762
Arm/Group Description	AUY922 Plasma Concentration	AUY Metabolite
Measure Participants	144	144
Mean (Standard Deviation) [ng/mL]	1130.59 (705.177)	2332.86 (1377.350)

Adverse Events

Arm/Group Title	KRAS Mutant		EGFR Mutant		KRAS and EGFR Wild Type		EML4-ALK Translocation		Modified EGFR Mutant
Arm/Group Description	Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m^2 weekly infusions.		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.		Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m^2 weekly infusions.		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.		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.
All Cause Mortality
	KRAS Mutant		EGFR Mutant		KRAS and EGFR Wild Type		EML4-ALK Translocation		Modified EGFR Mutant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	KRAS Mutant		EGFR Mutant		KRAS and EGFR Wild Type		EML4-ALK Translocation		Modified EGFR Mutant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/28 (60.7%)		18/35 (51.4%)		22/34 (64.7%)		6/22 (27.3%)		11/31 (35.5%)		2/3 (66.7%)
Blood and lymphatic system disorders
Anaemia	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Cardiac disorders
Atrial Fibrillation	0/28 (0%)		1/35 (2.9%)		2/34 (5.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Bundle Branch Block Right	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Cardio-Respiratory Arrest	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Palpitations	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Pericardial Effusion	0/28 (0%)		1/35 (2.9%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Supraventricular Tachycardia	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Tachycardia	0/28 (0%)		1/35 (2.9%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Eye disorders
Night Blindness	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Gastrointestinal disorders
Abdominal Distension	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		1/3 (33.3%)
Diarrhoea	1/28 (3.6%)		3/35 (8.6%)		1/34 (2.9%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Proctalgia	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Rectal Fissure	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Vomiting	1/28 (3.6%)		1/35 (2.9%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
General disorders
Asthenia	0/28 (0%)		1/35 (2.9%)		2/34 (5.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Fatigue	0/28 (0%)		0/35 (0%)		2/34 (5.9%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
General Physical Health Deterioration	1/28 (3.6%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Mucosal Inflammation	0/28 (0%)		1/35 (2.9%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Oedema Peripheral	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Pain	1/28 (3.6%)		2/35 (5.7%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Pyrexia	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Hepatobiliary disorders
Cholelithiasis	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Hyperbilirubinaemia	0/28 (0%)		1/35 (2.9%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Infections and infestations
Atypical Pneumonia	0/28 (0%)		0/35 (0%)		0/34 (0%)		1/22 (4.5%)		0/31 (0%)		0/3 (0%)
Bronchitis	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Klebsiella Infection	0/28 (0%)		1/35 (2.9%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Lung Infection	0/28 (0%)		0/35 (0%)		0/34 (0%)		1/22 (4.5%)		0/31 (0%)		0/3 (0%)
Perirectal Abscess	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Pneumonia	3/28 (10.7%)		1/35 (2.9%)		1/34 (2.9%)		1/22 (4.5%)		0/31 (0%)		1/3 (33.3%)
Respiratory Tract Infection	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		1/22 (4.5%)		0/31 (0%)		0/3 (0%)
Urinary Tract Infection	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Metabolism and nutrition disorders
Decreased Appetite	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Dehydration	1/28 (3.6%)		1/35 (2.9%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Failure To Thrive	1/28 (3.6%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Fluid Intake Reduced	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Hypercalcaemia	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Hyperglycaemia	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Hyperkalaemia	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Hyponatraemia	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Bone Pain	1/28 (3.6%)		1/35 (2.9%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Musculoskeletal Pain	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Neck Pain	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases To Central Nervous System	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Metastatic Pain	0/28 (0%)		1/35 (2.9%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Nervous system disorders
Balance Disorder	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Brain Compression	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Nervous System Disorder	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Spinal Cord Compression	0/28 (0%)		1/35 (2.9%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Vocal Cord Paresis	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Psychiatric disorders
Confusional State	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Depression	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		1/22 (4.5%)		0/31 (0%)		0/3 (0%)
Dyspnoea	3/28 (10.7%)		2/35 (5.7%)		2/34 (5.9%)		3/22 (13.6%)		0/31 (0%)		0/3 (0%)
Haemoptysis	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		1/22 (4.5%)		0/31 (0%)		0/3 (0%)
Hypoxia	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Pleural Effusion	0/28 (0%)		1/35 (2.9%)		1/34 (2.9%)		0/22 (0%)		4/31 (12.9%)		0/3 (0%)
Pneumothorax	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Pulmonary Embolism	1/28 (3.6%)		3/35 (8.6%)		1/34 (2.9%)		1/22 (4.5%)		0/31 (0%)		0/3 (0%)
Respiratory Failure	0/28 (0%)		2/35 (5.7%)		0/34 (0%)		1/22 (4.5%)		0/31 (0%)		0/3 (0%)
Vascular disorders
Deep Vein Thrombosis	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Hypertension	0/28 (0%)		2/35 (5.7%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Thrombosis	1/28 (3.6%)		1/35 (2.9%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	KRAS Mutant		EGFR Mutant		KRAS and EGFR Wild Type		EML4-ALK Translocation		Modified EGFR Mutant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/28 (100%)		35/35 (100%)		33/34 (97.1%)		22/22 (100%)		31/31 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	1/28 (3.6%)		3/35 (8.6%)		5/34 (14.7%)		3/22 (13.6%)		4/31 (12.9%)		0/3 (0%)
Lymphadenopathy	0/28 (0%)		0/35 (0%)		2/34 (5.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Lymphopenia	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		2/31 (6.5%)		0/3 (0%)
Cardiac disorders
Tachycardia	0/28 (0%)		2/35 (5.7%)		1/34 (2.9%)		1/22 (4.5%)		0/31 (0%)		0/3 (0%)
Ear and labyrinth disorders
Ear Pain	0/28 (0%)		1/35 (2.9%)		2/34 (5.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Vertigo	0/28 (0%)		1/35 (2.9%)		2/34 (5.9%)		2/22 (9.1%)		1/31 (3.2%)		0/3 (0%)
Eye disorders
Accommodation Disorder	1/28 (3.6%)		2/35 (5.7%)		2/34 (5.9%)		2/22 (9.1%)		5/31 (16.1%)		0/3 (0%)
Blepharitis	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		2/31 (6.5%)		0/3 (0%)
Cataract Subcapsular	1/28 (3.6%)		0/35 (0%)		2/34 (5.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Colour Blindness Acquired	0/28 (0%)		3/35 (8.6%)		2/34 (5.9%)		5/22 (22.7%)		4/31 (12.9%)		1/3 (33.3%)
Dry Eye	2/28 (7.1%)		0/35 (0%)		1/34 (2.9%)		2/22 (9.1%)		0/31 (0%)		0/3 (0%)
Eye Pain	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		2/31 (6.5%)		0/3 (0%)
Lacrimation Increased	0/28 (0%)		2/35 (5.7%)		0/34 (0%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Loss Of Visual Contrast Sensitivity	0/28 (0%)		0/35 (0%)		2/34 (5.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Night Blindness	3/28 (10.7%)		10/35 (28.6%)		6/34 (17.6%)		5/22 (22.7%)		10/31 (32.3%)		1/3 (33.3%)
Ocular Toxicity	4/28 (14.3%)		4/35 (11.4%)		1/34 (2.9%)		3/22 (13.6%)		3/31 (9.7%)		1/3 (33.3%)
Photophobia	3/28 (10.7%)		2/35 (5.7%)		5/34 (14.7%)		0/22 (0%)		2/31 (6.5%)		0/3 (0%)
Photopsia	3/28 (10.7%)		5/35 (14.3%)		10/34 (29.4%)		10/22 (45.5%)		6/31 (19.4%)		0/3 (0%)
Retinal Disorder	1/28 (3.6%)		3/35 (8.6%)		1/34 (2.9%)		5/22 (22.7%)		7/31 (22.6%)		0/3 (0%)
Vision Blurred	5/28 (17.9%)		6/35 (17.1%)		7/34 (20.6%)		6/22 (27.3%)		6/31 (19.4%)		0/3 (0%)
Visual Acuity Reduced	1/28 (3.6%)		6/35 (17.1%)		7/34 (20.6%)		7/22 (31.8%)		5/31 (16.1%)		0/3 (0%)
Visual Impairment	6/28 (21.4%)		8/35 (22.9%)		3/34 (8.8%)		6/22 (27.3%)		7/31 (22.6%)		0/3 (0%)
Vitreous Floaters	1/28 (3.6%)		3/35 (8.6%)		1/34 (2.9%)		1/22 (4.5%)		2/31 (6.5%)		1/3 (33.3%)
Gastrointestinal disorders
Abdominal Distension	0/28 (0%)		0/35 (0%)		2/34 (5.9%)		2/22 (9.1%)		0/31 (0%)		1/3 (33.3%)
Abdominal Pain	5/28 (17.9%)		5/35 (14.3%)		4/34 (11.8%)		6/22 (27.3%)		2/31 (6.5%)		0/3 (0%)
Abdominal Pain Upper	1/28 (3.6%)		3/35 (8.6%)		2/34 (5.9%)		0/22 (0%)		2/31 (6.5%)		0/3 (0%)
Constipation	6/28 (21.4%)		6/35 (17.1%)		5/34 (14.7%)		5/22 (22.7%)		5/31 (16.1%)		0/3 (0%)
Diarrhoea	25/28 (89.3%)		23/35 (65.7%)		25/34 (73.5%)		17/22 (77.3%)		24/31 (77.4%)		3/3 (100%)
Dry Mouth	5/28 (17.9%)		4/35 (11.4%)		6/34 (17.6%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Dyspepsia	0/28 (0%)		1/35 (2.9%)		1/34 (2.9%)		4/22 (18.2%)		3/31 (9.7%)		1/3 (33.3%)
Flatulence	0/28 (0%)		2/35 (5.7%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Nausea	16/28 (57.1%)		19/35 (54.3%)		13/34 (38.2%)		11/22 (50%)		12/31 (38.7%)		1/3 (33.3%)
Oral Pain	0/28 (0%)		2/35 (5.7%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Rectal Haemorrhage	2/28 (7.1%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Stomatitis	1/28 (3.6%)		0/35 (0%)		2/34 (5.9%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Vomiting	13/28 (46.4%)		13/35 (37.1%)		4/34 (11.8%)		9/22 (40.9%)		4/31 (12.9%)		2/3 (66.7%)
General disorders
Asthenia	13/28 (46.4%)		14/35 (40%)		10/34 (29.4%)		10/22 (45.5%)		5/31 (16.1%)		1/3 (33.3%)
Catheter Site Pain	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		2/31 (6.5%)		0/3 (0%)
Chest Pain	1/28 (3.6%)		2/35 (5.7%)		0/34 (0%)		4/22 (18.2%)		0/31 (0%)		1/3 (33.3%)
Fatigue	7/28 (25%)		9/35 (25.7%)		13/34 (38.2%)		3/22 (13.6%)		15/31 (48.4%)		0/3 (0%)
Gait Disturbance	0/28 (0%)		2/35 (5.7%)		2/34 (5.9%)		2/22 (9.1%)		0/31 (0%)		0/3 (0%)
Non-Cardiac Chest Pain	1/28 (3.6%)		0/35 (0%)		2/34 (5.9%)		2/22 (9.1%)		1/31 (3.2%)		0/3 (0%)
Oedema Peripheral	2/28 (7.1%)		2/35 (5.7%)		1/34 (2.9%)		3/22 (13.6%)		3/31 (9.7%)		0/3 (0%)
Pain	1/28 (3.6%)		2/35 (5.7%)		6/34 (17.6%)		0/22 (0%)		1/31 (3.2%)		1/3 (33.3%)
Pyrexia	5/28 (17.9%)		3/35 (8.6%)		4/34 (11.8%)		6/22 (27.3%)		4/31 (12.9%)		2/3 (66.7%)
Infections and infestations
Conjunctivitis	0/28 (0%)		0/35 (0%)		0/34 (0%)		2/22 (9.1%)		1/31 (3.2%)		0/3 (0%)
Influenza	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		3/31 (9.7%)		0/3 (0%)
Nasopharyngitis	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		1/22 (4.5%)		4/31 (12.9%)		1/3 (33.3%)
Respiratory Tract Infection	0/28 (0%)		0/35 (0%)		2/34 (5.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Upper Respiratory Tract Infection	0/28 (0%)		2/35 (5.7%)		1/34 (2.9%)		2/22 (9.1%)		4/31 (12.9%)		0/3 (0%)
Urinary Tract Infection	1/28 (3.6%)		2/35 (5.7%)		0/34 (0%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Investigations
Alanine Aminotransferase Increased	1/28 (3.6%)		2/35 (5.7%)		1/34 (2.9%)		1/22 (4.5%)		0/31 (0%)		0/3 (0%)
Aspartate Aminotransferase Increased	0/28 (0%)		1/35 (2.9%)		1/34 (2.9%)		2/22 (9.1%)		2/31 (6.5%)		0/3 (0%)
Blood Alkaline Phosphatase Increased	0/28 (0%)		4/35 (11.4%)		1/34 (2.9%)		1/22 (4.5%)		3/31 (9.7%)		0/3 (0%)
Blood Creatinine Increased	0/28 (0%)		0/35 (0%)		0/34 (0%)		1/22 (4.5%)		1/31 (3.2%)		1/3 (33.3%)
C-Reactive Protein Increased	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		2/31 (6.5%)		1/3 (33.3%)
Gamma-Glutamyltransferase Increased	0/28 (0%)		2/35 (5.7%)		1/34 (2.9%)		0/22 (0%)		3/31 (9.7%)		0/3 (0%)
Heart Rate Increased	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		1/3 (33.3%)
Hypophonesis	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		2/22 (9.1%)		0/31 (0%)		0/3 (0%)
Transaminases Increased	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		2/31 (6.5%)		0/3 (0%)
Weight Decreased	4/28 (14.3%)		1/35 (2.9%)		3/34 (8.8%)		1/22 (4.5%)		4/31 (12.9%)		0/3 (0%)
Metabolism and nutrition disorders
Decreased Appetite	17/28 (60.7%)		15/35 (42.9%)		12/34 (35.3%)		8/22 (36.4%)		10/31 (32.3%)		1/3 (33.3%)
Dehydration	1/28 (3.6%)		1/35 (2.9%)		3/34 (8.8%)		1/22 (4.5%)		1/31 (3.2%)		0/3 (0%)
Hyperglycaemia	1/28 (3.6%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		1/31 (3.2%)		1/3 (33.3%)
Hypokalaemia	2/28 (7.1%)		2/35 (5.7%)		0/34 (0%)		2/22 (9.1%)		1/31 (3.2%)		0/3 (0%)
Hypomagnesaemia	1/28 (3.6%)		2/35 (5.7%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Hyponatraemia	2/28 (7.1%)		4/35 (11.4%)		0/34 (0%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/28 (3.6%)		4/35 (11.4%)		2/34 (5.9%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Back Pain	8/28 (28.6%)		5/35 (14.3%)		8/34 (23.5%)		3/22 (13.6%)		7/31 (22.6%)		0/3 (0%)
Bone Pain	0/28 (0%)		2/35 (5.7%)		1/34 (2.9%)		1/22 (4.5%)		3/31 (9.7%)		0/3 (0%)
Flank Pain	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		4/31 (12.9%)		0/3 (0%)
Muscle Spasms	2/28 (7.1%)		1/35 (2.9%)		1/34 (2.9%)		3/22 (13.6%)		0/31 (0%)		0/3 (0%)
Musculoskeletal Chest Pain	1/28 (3.6%)		2/35 (5.7%)		2/34 (5.9%)		1/22 (4.5%)		2/31 (6.5%)		0/3 (0%)
Musculoskeletal Pain	3/28 (10.7%)		2/35 (5.7%)		5/34 (14.7%)		1/22 (4.5%)		2/31 (6.5%)		1/3 (33.3%)
Myalgia	0/28 (0%)		4/35 (11.4%)		4/34 (11.8%)		5/22 (22.7%)		6/31 (19.4%)		1/3 (33.3%)
Neck Pain	2/28 (7.1%)		0/35 (0%)		4/34 (11.8%)		1/22 (4.5%)		2/31 (6.5%)		1/3 (33.3%)
Pain In Extremity	2/28 (7.1%)		4/35 (11.4%)		4/34 (11.8%)		1/22 (4.5%)		1/31 (3.2%)		0/3 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		1/3 (33.3%)
Nervous system disorders
Ataxia	0/28 (0%)		0/35 (0%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		1/3 (33.3%)
Balance Disorder	1/28 (3.6%)		0/35 (0%)		0/34 (0%)		1/22 (4.5%)		3/31 (9.7%)		0/3 (0%)
Dizziness	1/28 (3.6%)		2/35 (5.7%)		1/34 (2.9%)		1/22 (4.5%)		3/31 (9.7%)		1/3 (33.3%)
Dysgeusia	2/28 (7.1%)		1/35 (2.9%)		1/34 (2.9%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Headache	8/28 (28.6%)		8/35 (22.9%)		8/34 (23.5%)		14/22 (63.6%)		13/31 (41.9%)		2/3 (66.7%)
Hypoaesthesia	0/28 (0%)		0/35 (0%)		2/34 (5.9%)		2/22 (9.1%)		2/31 (6.5%)		0/3 (0%)
Memory Impairment	2/28 (7.1%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Neuralgia	0/28 (0%)		3/35 (8.6%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Neuropathy Peripheral	0/28 (0%)		0/35 (0%)		2/34 (5.9%)		0/22 (0%)		1/31 (3.2%)		0/3 (0%)
Paraesthesia	0/28 (0%)		0/35 (0%)		2/34 (5.9%)		3/22 (13.6%)		3/31 (9.7%)		0/3 (0%)
Peripheral Sensory Neuropathy	0/28 (0%)		0/35 (0%)		2/34 (5.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Somnolence	1/28 (3.6%)		1/35 (2.9%)		2/34 (5.9%)		2/22 (9.1%)		0/31 (0%)		0/3 (0%)
Psychiatric disorders
Anxiety	2/28 (7.1%)		2/35 (5.7%)		3/34 (8.8%)		2/22 (9.1%)		2/31 (6.5%)		0/3 (0%)
Depressed Mood	0/28 (0%)		1/35 (2.9%)		2/34 (5.9%)		2/22 (9.1%)		0/31 (0%)		0/3 (0%)
Hallucination	0/28 (0%)		0/35 (0%)		0/34 (0%)		2/22 (9.1%)		0/31 (0%)		0/3 (0%)
Insomnia	0/28 (0%)		3/35 (8.6%)		6/34 (17.6%)		5/22 (22.7%)		4/31 (12.9%)		0/3 (0%)
Nervousness	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		2/22 (9.1%)		0/31 (0%)		0/3 (0%)
Reproductive system and breast disorders
Pelvic Pain	0/28 (0%)		2/35 (5.7%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		2/31 (6.5%)		0/3 (0%)
Cough	5/28 (17.9%)		8/35 (22.9%)		9/34 (26.5%)		7/22 (31.8%)		8/31 (25.8%)		1/3 (33.3%)
Dysphonia	0/28 (0%)		1/35 (2.9%)		2/34 (5.9%)		1/22 (4.5%)		1/31 (3.2%)		0/3 (0%)
Dyspnoea	5/28 (17.9%)		11/35 (31.4%)		9/34 (26.5%)		2/22 (9.1%)		2/31 (6.5%)		1/3 (33.3%)
Dyspnoea Exertional	0/28 (0%)		2/35 (5.7%)		2/34 (5.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Epistaxis	0/28 (0%)		0/35 (0%)		1/34 (2.9%)		0/22 (0%)		0/31 (0%)		1/3 (33.3%)
Haemoptysis	4/28 (14.3%)		3/35 (8.6%)		4/34 (11.8%)		1/22 (4.5%)		0/31 (0%)		0/3 (0%)
Oropharyngeal Pain	0/28 (0%)		1/35 (2.9%)		1/34 (2.9%)		0/22 (0%)		3/31 (9.7%)		0/3 (0%)
Pleural Effusion	0/28 (0%)		2/35 (5.7%)		3/34 (8.8%)		2/22 (9.1%)		2/31 (6.5%)		0/3 (0%)
Productive Cough	1/28 (3.6%)		4/35 (11.4%)		7/34 (20.6%)		2/22 (9.1%)		1/31 (3.2%)		0/3 (0%)
Rhinorrhoea	0/28 (0%)		2/35 (5.7%)		2/34 (5.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Wheezing	0/28 (0%)		2/35 (5.7%)		0/34 (0%)		1/22 (4.5%)		0/31 (0%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Dermatitis Acneiform	0/28 (0%)		0/35 (0%)		0/34 (0%)		1/22 (4.5%)		2/31 (6.5%)		0/3 (0%)
Dry Skin	1/28 (3.6%)		3/35 (8.6%)		1/34 (2.9%)		0/22 (0%)		4/31 (12.9%)		0/3 (0%)
Pain Of Skin	0/28 (0%)		0/35 (0%)		2/34 (5.9%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Pruritus	2/28 (7.1%)		1/35 (2.9%)		1/34 (2.9%)		1/22 (4.5%)		4/31 (12.9%)		0/3 (0%)
Rash	2/28 (7.1%)		2/35 (5.7%)		0/34 (0%)		1/22 (4.5%)		1/31 (3.2%)		0/3 (0%)
Vascular disorders
Deep Vein Thrombosis	0/28 (0%)		2/35 (5.7%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)
Hot Flush	1/28 (3.6%)		0/35 (0%)		1/34 (2.9%)		2/22 (9.1%)		1/31 (3.2%)		0/3 (0%)
Hypertension	0/28 (0%)		4/35 (11.4%)		3/34 (8.8%)		3/22 (13.6%)		5/31 (16.1%)		0/3 (0%)
Hypotension	0/28 (0%)		2/35 (5.7%)		0/34 (0%)		0/22 (0%)		0/31 (0%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.