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

A Multicenter, Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations Who Have Progressed on Prior EGFR TKI Treatment

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Non Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: AUY922; Drug: Docetaxel; Drug: Pemetrexed

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94000
    • Novartis Investigative Site
  • Villejuif Cedex, France, 94805
    • Novartis Investigative Site
  • Bouches Du Rhone
    • Marseille cedex 20, Bouches Du Rhone, France, 13915
      • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Novartis Investigative Site
• Italy
  • MB
    • Monza, MB, Italy, 20900
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
  • PR
    • Parma, PR, Italy, 43100
      • Novartis Investigative Site
  • TO
    • Orbassano, TO, Italy, 10043
      • Novartis Investigative Site
• Japan
  • Tokyo
    • Koto ku, Tokyo, Japan, 135 8550
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Korea
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 06351
      • Novartis Investigative Site
  • Seocho Gu
    • Seoul, Seocho Gu, Korea, Republic of, 06591
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Novartis Investigative Site
  • Groningen, Netherlands, 9713 GZ
    • Novartis Investigative Site
• Norway
  • Bergen, Norway, 5021
    • Novartis Investigative Site
  • Oslo, Norway, NO-0424
    • Novartis Investigative Site
• Poland
  • Gdansk, Poland, 80 952
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• Taiwan
  • Taichung, Taiwan, 407
    • Novartis Investigative Site
  • Taipei, Taiwan, 10048
    • Novartis Investigative Site
  • Taoyuan/ Taiwan ROC
    • Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, Taiwan, 33305
      • Novartis Investigative Site
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Novartis Investigative Site
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center Dept.of Cedars-Sinai Med. Ctr.
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Maryland Oncology Hematology, P.A. SC
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 5

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with histologically or cytologically documented, locally advanced (stage IIIB who are not amenable to combined modality treatment) or recurrent or metastatic (Stage IV) non-small cell lung cancer.

2. Patients must have EGFR gene mutation in their tumors. This can be source - documented by one of the following:

   • Provide a pathology report that indicates the patient's tumor had EGFR activating mutation in the past.

   Or:

   • Perform testing (local or central) in an archival tumor or a fresh baseline biopsy tumor tissue to show the presence of EGFR activating mutation.

3. Patients must have documented clinical benefit (CR, PR, or patients with SD for 6 months or greater) on prior EGFR TKI (e.g. erlotinib or gefitinib) followed by documented progression according to RECIST.
4. Patients must have received prior platinum containing treatment.
5. WHO performance status of 0-1

Exclusion Criteria:

1. Patients who have received more than two prior lines of antineoplastic therapy for advanced disease. Chemotherapy administered as neoadjuvant or adjuvant treatment more than six months prior to study enrollment is not considered a prior line of therapy for purposes of this study.
2. Evidence of spinal cord compression or current evidence of CNS metastases. Screening CT/MRI of the brain is mandatory. Note: Patients who have been treated for CNS metastases by radiation or gamma knife surgery, who been stable for at least 2 months and have discontinued high dose corticosteroids will be eligible for protocol participation
3. Prior treatment with an HSP90 inhibitor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AUY922 arm; Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm. AUY922 was to be administered weekly.	Drug: AUY922; AUY922 was to be given by i.v. once weekly at 70 mg/m2 until disease progression, death or any other reason for discontinuation from study treatment.
Active Comparator: chemotherapy arm; Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm. Pemetrexed or docetaxel was to be was to be given once every three weeks.	Drug: Docetaxel; Docetaxel was to be given i.v. once every 3 weeks at 75 mg/m2 until progression or unacceptable toxicity; Other Names: TAXOTERE; Drug: Pemetrexed; Pemetrexed was to be given once every 3 weeks at 500 mg/m2 until progression or unacceptable toxicity; Other Names: ALIMTA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	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 target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	16 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	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 the efficacy assessments was stopped at that time.	16 months
Overall Survival (OS)	OS is defined as the time from the date of randomization to date of death due to any cause. If a death has not been observed by the date of analysis cutoff, then OS was to be censored at the last known date patient was alive.	from randomization until death up to death
Disease Control Rate (DCR)	Duration of DCR will be compared between treatment arms. The duration of DCR will be based on local investigator assessment per RECIST 1.1	baseline, until disease progression up to 24 months
Time to Response (TRR)	TTR was to compare between treatment arms. The TTR was to be based on local investigator assessment per RECIST 1.1	baseline, until disease progression up to 24 months
Duration of Response (DOR)	The DOR will be compared between treatment arms. The DOR will be based on local investigator assessment per RECIST 1.1	baseline, until disease progression up to 24 months
Rate of Adverse Events (AEs)	To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.	baseline, until disease progression up to 24 months
Change in Laboratory Paramenters	Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity.	baseline, until disease progression up to 24 months
Time to Progression (TTP)	TTP will be compared between treatment arms. The TTP will be based on local investigator assessment per RECIST 1.1	baseline, until disease progression up to 24 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2012
• Primary Completion (Actual): November 4, 2015
• Study Completion (Actual): November 4, 2015

Study Registration Dates

• First Submitted: June 26, 2012
• First Submitted That Met QC Criteria: July 19, 2012
• First Posted (Estimate): July 20, 2012

Study Record Updates

• Last Update Posted (Actual): July 24, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Docetaxel; NSCLC; lung cancer; Non-small cell lung cancer; Pemetrexed; EGFR mutations; lung adenocarcinoma; Non small cell lung cancer; Non-small cell lung carcinoma (NSCLC); treatment of lung cancer after first metastasis; Non small cell lung carcinoma; EGFR TKI; Large-cell lung carcinoma; Large cell lung carcinoma; Large cell lung cancer; Squamous cell lung carcinoma; HSP90; AUY922
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Folic Acid Antagonists; Docetaxel; Pemetrexed
• Other Study ID Numbers: CAUY922A2207; 2012-001050-25 (EudraCT Number)