1248P_PR - The galaxy trial (NCT01348126): a randomized IIB/III study of ganetespib (STA-9090) in combination with docetaxel versus docetaxel alone as second l...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Suresh Ramalingam
Authors S.S. Ramalingam1, B. Zaric2, G. Goss3, C. Manegold4, R. Rosell5, V. Vukovic6, I. El-Hariry6, F. Teofilovici6, A. Enke6, D. Fennell7
  • 1Emory University Winship Cancer Institute, 30322 - Atlanta/US
  • 2Clinic For Pulmonary Oncology, Institute of Oncology Vojvodina, RS-21204 - Sremska Kamenica/YU
  • 3Medical Oncology, The Ottawa Hospital Cancer Centre, K1H 8L6 - Ottawa/CA
  • 4Dept. Of Surgery, University Medical Center, Mannheim/DE
  • 5Medical Oncology Service, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, 08916 - Badalona/ES
  • 6Clinical Development, Synta Pharmaceuticals Corp., US-02421 - Lexington/US
  • 7Synta Pharmaceuticals Corp., US-02421 - Lexington/US

Abstract

Background: Inhibition of Hsp90, a key molecular chaperone required for activation of many oncoproteins, can lead to cancer cell death. Ganetespib (G) is a resorcinolic 2nd generation Hsp90 inhibitor that has shown single agent activity in pretreated patients with advanced NSCLC harboring the ELM4-ALK rearrangement and KRAS mutations. Combination of G with docetaxel (D) results in synergistic activity in NSCLC xenografts and was well tolerated in a Phase I study.

Methods: The GALAXY trial is an international, randomized Phase IIB/III study. The Phase IIB stage (N=300) evaluates treatment with G plus D vs. D alone in 2nd line advanced NSCLC patients. Co-primary endpoints are PFS in the high LDH adenocarcinoma population and PFS in patients with mKRAS tumors. Main secondary endpoints include PFS and OS in adenocarcinoma patients, ORR, disease control rate, and clinical activity in genetically profiled subpopulations. All patients receive D 75 mg/m2 on day 1 of a three-week treatment cycle; combination arm patients receive G 150 mg/m2 on day 1 and day 15 in addition.

Results: As of April 2012, just over half of the 300 planned patients were enrolled. Baseline characteristics were balanced. Tumor tissue was obtained in ~90% of patients. In the combination arm, 1-4% of patients had transient Gr 3\4 GI and liver toxicities; Gr 1\2 ocular toxicities were observed in <3% of patients. The overall safety profile of the combination is comparable to docetaxel single agent. An early signal of activity was observed in two pre-specified patient populations. Results from a planned interim analysis in early September, including efficacy results in subpopulations, will be presented at the meeting.

Conclusions: Ganetespib in combination with docetaxel was well tolerated by patients with advanced NCSLC. Encouraging signals of activity in pre-specified patient populations have been observed.