Targeted therapy for advanced cancers based on genetic profiling

Inclusion Criteria: (screening step - non-drug specific)

* Adult (≥ 18 yrs) patient with a histologically-proven incurable metastatic solid tumour (excluding primary brain tumours), multiple myeloma or B cell non-Hodgkin lymphoma (excluding CLL, SLL and HCL), for whom there is no standard treatment known to prolong life, or who has refused such treatment.
* ECOG performance status 0-2.
* Patients must have normal organ function as follows:

  * Absolute neutrophil count: ≥ 1.5 x 10\^9/L for solid tumours; ≥ 1.0 x 10\^9/L for neurologic malignancies
  * Platelets ≥ 75 x 10\^9/L (or ≥ 50 x 10\^9/L if bone marrow involvement by myeloma or lymphoma).
  * Total bilirubin ≤ 1.5 x UNL.
  * AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal value unless liver metastases are present in which case they must be \< 5 x ULN;
  * Serum creatinine ≤ 1.5 x UNL or calculated or measured creatinine clearance ≥ 50mg/min/1.73µ\^2
* Patients must have measurable disease
* Results must be available from tumour genomic or protein expression testing (if used to identify genetic variants), from one of the initiatives / groups listed in protocol Appendix VII. The test may have been performed on the primary tumour or a metastatic deposit (including bone marrow), or blood, in a diagnostic or research laboratory and must reveal a potentially actionable variant.
* Patient consent (Main Study Consent for the screening step) must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to the screening step to document their willingness to participate
* Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre or a CCTG IND site. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial.
* Women/men of childbearing potential must have agreed to use a highly effective contraceptive method.

Exclusion Criteria: (screening step - non-drug specific)

* Patients with prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
* Patients with ongoing toxicity ≥ CTCAE grade 2, other than peripheral neuropathy or asymptomatic, corrected biochemical toxicities (e.g. hypothyroidism corrected by thyroid replacement), related to prior anti-tumour treatment. Patients with ongoing peripheral neuropathy of ≥ CTCAE grade 3 will be excluded.
* Patients concurrently receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) except for medications that are prescribed for supportive care but may potentially have an anti-cancer effect (e.g. megestrol acetate, bisphosphonates) or ongoing castration-intent therapy for prostate cancer. These medications must have been started ≥ one month prior to enrollment on this study. Patients may be on warfarin, low molecular weight heparin or direct factor Xa inhibitors, unless such therapies are prohibited by drug-specific ineligibility criteria.
* Patients with known active progressive brain metastases. Patients with previously treated brain metastases are eligible, provided that the patient has not experienced a seizure or had a clinically significant change in neurological status within one month prior to screening. All patients with previously treated brain metastases must be stable (clinically and radiologically) for at least one month after completion of treatment and either off steroid treatment or only taking physiological doses of steroids prior to the screening step.
* Patients with clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure.
* Patients with known left ventricular ejection fraction (LVEF) \< 40%.
* Patients with stroke (including TIA) or acute myocardial infarction within three months prior to the screening step.
* Patients with acute gastrointestinal bleeding within one month prior to the screening step.
* Patients with any other clinically significant medical condition which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements including, but not limited to: ongoing or active infection, significant uncontrolled hypertension, or severe psychiatric illness/social situations.
* Lactating and nursing women
* Patients who do not meet drug-specific eligibility requirements for the drug selected by the treating physician.