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NCT01646125

An Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations

Terminated Phase 2 Results posted Last updated 24 July 2019
What this trial tests

Phase 2 trial testing AUY922 in Advanced Non Small Cell Lung Cancer (NSCLC) in 59 participants. Terminated before completion.

Timeline
23 November 2012
Primary endpoint
4 November 2015
4 November 2015

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment59
Start date23 November 2012
Primary completion4 November 2015
Estimated completion4 November 2015
Sites27 locations across France, Hong Kong, Japan, Italy, Netherlands, Taiwan, United Kingdom, Poland

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Advanced Non Small Cell Lung Cancer (NSCLC). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) Primary · 16 months

Compared PFS between the treatment of AUY922 to comparators Pemetrexed or Docetaxel. Progression-free survival (PFS) based on local investigator assessment per RECIST 1.1 was 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 had not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of tar

GroupValue95% CI
AUY922 Arm1.51.2 – 5.6
Chemotherapy Arm2.31.2 – 4.0
Overall Response Rate (ORR) Secondary · 16 months

ORR was to be compared between treatment arms. The ORR was to be based on local investigator assessment per Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST 1.1). Per this criteria for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.This outcome measure was originally planned to be analyzed up to 24 months. The DMC recommendation at the IA was to stop the study for futility. As a result, collection of all

Complete Response (CR)
GroupValue95% CI
AUY922 Arm0
Chemotherapy Arm0
Partial Response (PR)
GroupValue95% CI
AUY922 Arm3
Chemotherapy Arm2
ORR (CR + PR)
GroupValue95% CI
AUY922 Arm3
Chemotherapy Arm2

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AUY922 Arm
Serious: 10/29 (34%)
Deaths:
Chemotherapy Arm
Serious: 6/23 (26%)
Deaths:
Total
Serious: 16/52 (31%)
Deaths:

Serious adverse events (20 terms)

ReactionSystemAUY922 ArmChemotherapy ArmTotal
PNEUMONIAInfections and infestations
ATRIAL FIBRILLATIONCardiac disorders
RETINAL DEGENERATIONEye disorders
VISION BLURREDEye disorders
CONSTIPATIONGastrointestinal disorders
STOMATITISGastrointestinal disorders
ASTHENIAGeneral disorders
DISCOMFORTGeneral disorders
PYREXIAGeneral disorders
SUDDEN DEATHGeneral disorders
LOCALISED INFECTIONInfections and infestations
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
URINARY TRACT INFECTIONInfections and infestations
FALLInjury, poisoning and procedural complications
DECREASED APPETITEMetabolism and nutrition disorders
ARTHRALGIAMusculoskeletal and connective tissue disorders
METASTASES TO CENTRAL NERVOUS SYSTEMNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DIZZINESSNervous system disorders
EPILEPSYNervous system disorders
HAEMOPTYSISRespiratory, thoracic and mediastinal disorders
Other adverse events (55 terms — click to expand)

ReactionSystemAUY922 ArmChemotherapy ArmTotal
DIARRHOEAGastrointestinal disorders
ASTHENIAGeneral disorders
FATIGUEGeneral disorders
NAUSEAGastrointestinal disorders
PHOTOPSIAEye disorders
HEADACHENervous system disorders
COUGHRespiratory, thoracic and mediastinal disorders
DYSPNOEARespiratory, thoracic and mediastinal disorders
CONSTIPATIONGastrointestinal disorders
BACK PAINMusculoskeletal and connective tissue disorders
PRURITUSSkin and subcutaneous tissue disorders
DECREASED APPETITEMetabolism and nutrition disorders
MYALGIAMusculoskeletal and connective tissue disorders
VISION BLURREDEye disorders
VISUAL IMPAIRMENTEye disorders
VOMITINGGastrointestinal disorders
PYREXIAGeneral disorders
ARTHRALGIAMusculoskeletal and connective tissue disorders
ALOPECIASkin and subcutaneous tissue disorders
RASHSkin and subcutaneous tissue disorders
ANAEMIABlood and lymphatic system disorders
MUSCULOSKELETAL PAINMusculoskeletal and connective tissue disorders
PAIN IN EXTREMITYMusculoskeletal and connective tissue disorders
HYPERTENSIONVascular disorders
STOMATITISGastrointestinal disorders
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
PARAESTHESIANervous system disorders
PERIPHERAL SENSORY NEUROPATHYNervous system disorders
LYMPHOPENIABlood and lymphatic system disorders
NEUTROPENIABlood and lymphatic system disorders
ABDOMINAL PAIN UPPERGastrointestinal disorders
DRY MOUTHGastrointestinal disorders
NON-CARDIAC CHEST PAINGeneral disorders
OEDEMA PERIPHERALGeneral disorders
CONJUNCTIVITISInfections and infestations
URINARY TRACT INFECTIONInfections and infestations
GAMMA-GLUTAMYLTRANSFERASE INCREASEDInvestigations
HYPERGLYCAEMIAMetabolism and nutrition disorders
INSOMNIAPsychiatric disorders
ACCOMMODATION DISORDEREye disorders

Most-reported serious reactions: PNEUMONIA, ATRIAL FIBRILLATION, RETINAL DEGENERATION, VISION BLURRED, CONSTIPATION, STOMATITIS, ASTHENIA, DISCOMFORT.

Data from ClinicalTrials.gov NCT01646125 adverse events section.

Sponsor's own description

The purpose of this study was to determine if AUY922 had superior efficacy when compared to chemotherapy agents docetaxel or pemetrexed in patients whose tumor had EGFR mutations. The primary purpose of this study was to compare the efficacy of AUY922, when administered i.v. on a once-weekly schedule at 70 mg/m2, versus docetaxel or pemetrexed in adult patients with advanced NSCLC, whose tumors harbored EGFR activating mutations, and had developed resistance to EGFR TKI.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer.
    Wu SG, Shih JY. · · 2018 · cited 577× · PMID 29455650 · DOI 10.1186/s12943-018-0777-1
  2. Heat shock protein 90 inhibitors in the treatment of cancer: current status and future directions.
    Jhaveri K, Ochiana SO, Dunphy MP, Gerecitano JF, et al · · 2014 · cited 128× · PMID 24669860 · DOI 10.1517/13543784.2014.902442
  3. Chaperone-assisted E3 ligase CHIP: A double agent in cancer.
    Kumar S, Basu M, Ghosh MK. · · 2022 · cited 29× · PMID 36157498 · DOI 10.1016/j.gendis.2021.08.003
  4. Management of acquired resistance to epidermal growth factor receptor kinase inhibitors in patients with advanced non-small cell lung cancer.
    Sacher AG, Jänne PA, Oxnard GR. · · 2014 · cited 27× · PMID 24752335 · DOI 10.1002/cncr.28723
  5. <sup>89</sup>Zr-Onartuzumab PET imaging of c-MET receptor dynamics.
    Pool M, Terwisscha van Scheltinga AGT, Kol A, Giesen D, et al · · 2017 · cited 22× · PMID 28315949 · DOI 10.1007/s00259-017-3672-x
  6. HSP90 as a novel molecular target in non-small-cell lung cancer.
    Esfahani K, Cohen V. · · 2016 · cited 21× · PMID 28210156 · DOI 10.2147/lctt.s60344
  7. Treating patients with ALK-positive non-small cell lung cancer: latest evidence and management strategy.
    Liao BC, Lin CC, Shih JY, Yang JC. · · 2015 · cited 20× · PMID 26327925 · DOI 10.1177/1758834015590593
  8. Treatment of Non-small Cell Lung Carcinoma after Failure of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor.
    Lee JC, Jang SH, Lee KY, Kim YC. · · 2013 · cited 20× · PMID 23864840 · DOI 10.4143/crt.2013.45.2.79

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