Once a recommended Phase II dose of Debio 0932 in combination with each of the 3 chemotherapy regimens described above has been identified, the randomized, double-blind, placebo-controlled Phase II portion of this study will then begin where approximately 140 eligible patients will be randomized to receive chemotherapy with either placebo or Debio 0932. The primary objective of the Phase II study is to determine the efficacy of Debio 0932 in combination with chemotherapy. The KRAS mutation status will also be assessed and used as a stratification factor.
About Debio 0932
HSP90 is a chaperone protein that controls the folding and processing of certain client proteins. HSP90 clients include many proteins that drive tumor development and progression, such as EGFR, HER2, c-MET, AKT, KIT, FLT3, and VEGFR. Inhibition of HSP90 leads to degradation of client proteins targeting multiple oncogenic signaling pathways.
Debio 0932 is an oral second-generation HSP90 inhibitor, which has shown extended tumor retention, blood-brain-barrier penetration, and promising anti-tumor activity both as monotherapy and in combination against a broad range of tumors in pre-clinical models.
Debiopharm presented data from the dose escalation portion of an ongoing Phase I clinical trial study at the annual meeting of the American Society of Clinical Oncology in June 2012. Debio 0932 was generally well tolerated in this study and showed promising signs of anti-tumor activity in patients with advanced solid tumors, especially lung cancer. For further details see
. Debiopharm advanced Debio 0932 into the Phase Ib expansion portion of the study in the beginning of 2012. The objectives of this ongoing Phase Ib portion of the study are to further assess the safety profile, pharmacokinetics and pharmacodynamics of Debio 0932, and to make a preliminary assessment of anti-tumor activity in patients with advanced solid tumors, including patients with NSCLC.
In preclinical testing Debio 0932 demonstrated potent anti-proliferative activity against a broad range of cancer cell lines, including many NSCLC cell lines which are resistant to SOC agents. Debio 0932 potently inhibits tumor growth in subcutaneous xenograft models of a number of solid and hematological malignancies, including models of NSCLC which harbor mutations conferring acquired or primary erlotinib resistance. Furthermore, Debio 0932 is able to extend animal survival in models of brain metastasis due to its ability to cross the blood-brain barrier, and it enhances the activity of several SOC agents in animal models of cancer.