PI3K Inhibitor BYL719 in Combination With the HSP90 Inhibitor AUY922 in Patients With Advanced or Metastatic Gastric Cancer

Inclusion criteria

• Patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction;
• Patients must not have a complete gastrectomy;
• gastric tumors carrying PIK3CA mutation or amplification, or HER2-overexpression, or both;
• at least one but no more than three previous lines of treatment for advanced or metastatic disease;
• Patients with PIK3CA mutated or amplified tumors must have failed at least one line but no more than three lines of standard chemotherapy and/or targeted agents;Patients with HER2 amplified tumor must have failed at least one line, but no more than three lines, with or without anti-HER2 therapy. All HER2 positive patients are expected to have received trastuzumab unless contraindications were present or trastuzumab was unavailable;
• Performance Status (PS) ≤ 1 ;
• Adequate bone marrow, liver and other organ functions and laboratory parameters;
• Recovery from all AEs of previous anti-cancer therapies, including surgery and radiotherapy, to baseline or to CTCAE Grade ≤ 1, except for alopecia;Negative serum pregnancy (β hCG) test within 72 hrs before starting study treatment in all pre-menopausal women and women < 12 months after the onset of menopause.

• Exclusion Criteria:
• Progressive disease during or after prior combination treatment with PI3K-inhibitors and HSP90- inhibitors;
• history of prior significant toxicity from another PI3K- or HSP90- inhibitor requiring discontinuation of treatment;
• primary CNS tumor or uncontrolled CNS metastasest;
• Patients who are currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment;
• Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with fasting glucose ≥ 140 mg/dL / 7.8 mmol/L, history of clinically significant gestational diabetes mellitus or documented steroid-induced diabetes mellitus;Patients with diarrhea CTCAE Grade ≥ 2 ;
• Patients with acute or chronic pancreatitis; History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO;
• Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral BYL719;
• Patients receiving chronic slow-release formulation of Proton Pump Inhibitors (PPI), H2-antagonists or other gastric pH elevating agents;
• Treatment with therapeutic doses of coumarin-based anticoagulants (e.g., warfarin sodium, Coumadin®). Low doses of courmarin-based anticoagulants;
• Patients receiving chronic or high dose corticosteroids therapy; other protocol-defined inclusion/exclusion criteria may apply.