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

• Overall Survival (OS) [ Time Frame: from randomization until death up to death ] [ Designated as safety issue: No ]
  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 will be censored at the date of last contact.
• Overall Response Rate (ORR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
  ORR will be compared between treatment arms. The ORR will be based on local investigator assessment per RECIST 1.1
• Disease Control Rate (DCR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
  Duration of DCR will be compared between treatment arms. The duration of DCR will be based on local investigator assessment per RECIST 1.1
• Time to Progression (TTP) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
  TTP will be compared between treatment arms. The TTP will be based on local investigator assessment per RECIST 1.1
• Duration of Response (DOR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
  The DOR will be compared between treatment arms. The DOR will be based on local investigator assessment per RECIST 1.1
• Rate of Adverse Events (AEs) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: Yes ]
  To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.
• Rate of serious Adverse events (SAEs) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: Yes ]
  To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.
• Change in laboratory parameters [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: Yes ]
  Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity.

• Overall Survival (OS) [ Time Frame: from randomization until death up to 24 months ] [ Designated as safety issue: No ]
  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 will be censored at the date of last contact.
• Overall Response Rate (ORR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
  ORR will be compared between treatment arms. The ORR will be based on local investigator assessment per RECIST 1.1
• Disease Control Rate (DCR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
  Duration of DCR will be compared between treatment arms. The duration of DCR will be based on local investigator assessment per RECIST 1.1
• Time to Progression (TTP) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
  TTP will be compared between treatment arms. The TTP will be based on local investigator assessment per RECIST 1.1
• Duration of Response (DOR) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: No ]
  The DOR will be compared between treatment arms. The DOR will be based on local investigator assessment per RECIST 1.1
• Rate of Adverse Events (AEs) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: Yes ]
  To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.
• Rate of serious Adverse events (SAEs) [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: Yes ]
  To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.
• Change in laboratory parameters [ Time Frame: baseline, until disease progression up to 24 months ] [ Designated as safety issue: Yes ]
  Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity.

The purpose of this study is to determine if AUY922 has superior efficacy when compared to chemotherapy agents docetaxel or pemetrexed in patients whose tumor have EGFR mutations.

The primary purpose of this study is 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 harbor EGFR activating mutations, and have developed resistance to EGFR TKI.

• Drug: AUY922
• Drug: Docetaxel
  Docetaxel will be given i.v. once every 3 weeks at 75 mg/m2 until progression or unacceptable toxicity
  Other Name: TAXOTERE
• Drug: Pemetrexed
  Pemetrexed will be given once every 3 weeks at 500 mg/m2 until progression or unacceptable toxicity
  Other Name: ALIMTA

• Experimental: AUY922 arm
  AUY922 will be administered weekly
  Intervention: Drug: AUY922
• Active Comparator: chemotherapy arm
  docetaxel or pemetrexed will be given once every three weeks
  Interventions:

  • Drug: Docetaxel
  • Drug: Pemetrexed

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
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. Patients must be suitable and willing to undergo mandatory baseline biopsy according to treating institution's own guidelines and requirements for such procedure.

Exclusion Criteria:

1. Patients who have received more than two prior lines of antineoplastic therapy for advanced disease.
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

Other protocol-defined inclusion/exclusion criteria may apply