Try - a Phase Ii Study to Evaluate Safety and Efficacy of Combined Trastuzumab and the Hsp90 Inhibitor Auy922 in Advanced Non-Small-Cell Lung Cancer (Nsclc) with Her2 Overexpression or Amplification or Mutation

Abstract

ABSTRACT Aim: Mutations and/or amplifications of HER2 can be found in approximately 4% of patients with NSCLC. In patients with NSCLC and amplification of HER2, identified by immunohistochemistry (IHC3+) or positive fluorescence in situ hybridization (FISH), preliminary clinical data suggests efficacy of trastuzumab. AUY922 is an inhibitor of the heat shock protein HSP90. This protein acts as molecular chaperone for processing and transport of various intracellular proteins including HER2. AUY922 has shown single agent activity in patients suffering from HER2 amplified breast cancer. This trial investigates the efficacy of trastuzumab combined with AUY922 in patients with NSCLC. Methods: Patients with metastatic NSCLC and overexpression or amplification of HER2 (IHC DAKO 3+ or positive FISH) or activating mutation after failure of at least one standard treatment are enrolled for combination treatment with trastuzumab and AUY922 in this bicentric phase II study (study centers Cologne and Essen). Treatment starts as monotherapy with trastuzumab, restaging is performed every 6 weeks by CT scan. AUY922 is added at 70mg/m2 once weekly once progression occurs. The primary endpoint is response rate of combination therapy. Results: We screened 3,863 patients with NSCLC within the Network of Genomic Medicine for amplification or mutation of HER2 in Cologne; patients in Essen were screened separately. An amplification was detected in 4% of these patients, mutations occurred in 1.6%. So far, 5 patients have been treated within the ongoing trial. One patient is currently being treated with trastuzumab monotherapy and has shown stable disease in the third restaging after 18 weeks of treatment. The preliminary best response to combination therapy is disease stabilization for 12 weeks until progression, the maximum reduction in tumor volume is -29.3%, six weeks after start of combination therapy. Conclusions: Patients with NSCLC and amplified/mutated HER2 are treated with trastuzumab and AUY922 in this ongoing study. We will present preliminary data of clinical outcome and tolerability of this treatment. Disclosure: L. Nogova: Honoraria by Roche, Travel grant by Novartis; M. Schuler: Advisory Board/Consultant: AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer Research grants: Boehringer Ingelheim, Novartis Honoraries: Alexion, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Lilly, Novartis, Pfizer; J. Wolf: Advisory boards (compensated) and lecture fees: AstraZeneca, BMS, Boehringer-Ingelheim, Clovis, Novartis, Pfizer, Roche Research support: Bayer, Boehringer-Ingelheim, Novartis, Pfizer, Roche. All other authors have declared no conflicts of interest.