An open non-randomized study using biology driven selection of therapies. WINTHER study will explore matched tumoral and normal tissue biopsies and will use a novel method for predicting efficacy of drugs. The aim is to provide a rational personalized therapeutic choice to all (100 %) patients enrolled in the study, harboring oncogenic events (mutations/ translocations/ amplifications, etc.) or not. The total number of patients treated in the study will be two hundred across all participating cancer centers (European countries -France; Spain-, Israel, USA and Canada). All centers will realize the same study independently.

Inclusion Criteria:

• Informed consent
• Any histologic type of metastatic cancer, (except for lung and brain at US sites), in which histologic normal counterpart can be obtained.
• Progression by RECIST (Response Evaluation Criteria In Solid Tumors) or other criteria on at least one prior regimen for advanced disease.
• Ability to undergo a biopsy or surgical procedure to obtain fresh tumor biopsy paired with its normal counterpart.
• Age from 18 years
• Life expectancy of at least 3 months
• ECOG Performance status of 0 to 1
• Measurable or evaluable disease according to RECIST 1.1 criteria
• For U.S. sites, advanced cancer patients that have exhausted all effective therapy for their disease and have progressed after previous line of therapy (documented disease progression under last treatment received) and conventional methods of assigning new therapy would not be expected to increase survival by more than 3 months.

Exclusion Criteria:

• Any patient that might require a lung or brain biopsy are excluded (at US sites)

• Alteration of organ function or hematopoietic function as defined by the following criteria:

  1. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) >2.5 x upper limit of normal (ULN), except for patients with liver metastases, for which AST and ALT > 5.0 ULN is the exclusion criteria.
  2. Bilirubin > 2.0 ULN
  3. Polynuclear neutrophil < 1.5 x 109/L
  4. Platelets < 100 x 10 9/L
  5. Hemoglobin < 90 g/L
  6. Creatinine > 1.5 ULN
  7. Calcemia > 1.5 ULN
  8. Phosphatemia > 1.5 ULN

• Coagulation abnormality prohibiting a biopsy

• Symptomatic or progressive brain metastases detected by radio imaging, or meningeal

• Patient who received a personalized therapeutic treatment based on molecular anomaly during the treatment period prior to the WINTHER directed treatment (defining the PFS1). Hormonal therapy may be continued during WINTHER suggested therapy. The exclusion of prior matched targeted therapy includes but is not limited to all targeted therapeutics that are EMA approved and genomically matched to patients. If there are questions about whether or not a prior therapy is matched targeted treatment it will be agreed on by discussion between PIs who are also Clinical Management Committee members; the resolution should take place prior to starting WINTHER directed treatment.