• Patient (age≥ 18 years) with a histologically-proven locally advanced or metastatic malignant disease who is no longer benefitting from standard anti-cancer treatment or for whom, in the opinion of the investigator, no such treatment is available or indicated.

• ECOG performance status 0-2

• Patients must have acceptable organ function as defined below. However, as noted above, drug-specific inclusion/exclusion criteria specified in the appendix for each agent will take precedence for this and all inclusion criteria:

‣ Absolute neutrophil count ≥ 1500 µl

⁃ Hemoglobin \> 5.6 mmol/l

⁃ Platelets \> 75,000/µl

⁃ Total bilirubin \< 1.5 x institutional upper limit of normal (ULN)

⁃ AST (SGOT) and ALT(SGPT) \< 2.5 x institutional upper limit of normal (ULN) (or \< 5 x ULN in patients with known hepatic metastases)

⁃ Calculated or measured creatinine clearance ≥ 50 mL/min/1.73 m2.

• Patients must have measurable or evaluable disease (per RECIST v1.1 for solid tumor), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or a subcutaneous or superficial lesion that can be measured with calipers by clinical exam. For lymph nodes, the short axis must be ≥15 mm. Patients who have assessable disease by physical or radiographic examination but do not meet these definitions of measurable disease are eligible and will be considered to have evaluable disease. Patient's whose disease cannot be objectively measured by physical or radiographic examination (e.g., elevated serum tumor marker only) are NOT eligible, with the exception of CA-125 for ovarian cancer and PSA for prostate cancer.

• Results must be available from a genomic test or immunohistochemistry (IHC) test for protein expression performed in a laboratory accredited by the competent local regulatory authority. The genomic or IHC test used to qualify a patient for participation in ProTarget may have been performed on any specimen of the patient's tumor obtained at any point during the patient's care at the discretion of the patient's treating physician. Genomic assays performed on cell-free DNA in plasma (liquid biopsies) will also be acceptable if the genomic analysis is performed in a laboratory accredited by the competent local regulatory authority.

• A new biopsy must be performed if possible, for central confirmation by WGS (the result may be awaited and is not required before first dosing).

• Note: Eligible genomic tests may include any of the following technologies: fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), comparative genomic hybridization (CGH), next generation sequencing (NGS), whole exome sequencing (WES). The test may have been performed on a fresh (frozen or in RNA-later) or paraffin-embedded specimen of the primary tumor or a metastatic deposit or on cell free DNA derived from plasma, as determined by the treating physician, and must reveal a potentially actionable genomic variant as defined in Section 5.0, or protein overexpression by IHC.

• Ability to understand and the willingness to sign a written informed consent/assent document

• Have a tumor genomic profile for which treatment with one of the approved targeted anti-cancer therapies included in this study has potential clinical benefit based on the criteria described in Section 7.0.

• For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.

• Because of the risks of drug treatment to the developing fetus, women of child-bearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) in combination with inhibition of ovulation (intrauterine device (IUD), intrauterine hormone-releasing system ( IUS), bilateral tubal occlusion, vasectomized partner or sexual abstinence) for the duration of study participation, and for four to 24 months following completion of study therapy (depending on SPC from individual drugs). Should a woman become pregnant or suspect she is pregnant while participating in this study or if she is the partner of a male participant in this study and becomes pregnant while he is participating in this study, she should inform her or her partner's treating physician immediately as well as her obstetrician. Female study patients who become pregnant must immediately discontinue treatment with any study therapy. Male patients should avoid impregnating a female partner. Male study patients, even if surgically sterilized, (i.e. post-vasectomy) must agree to one of the following: practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or completely abstain from sexual intercourse.