Inclusion Criteria:
1. Adult (age \>18 years) patient with a histologically-confirmed locally advanced or metastatic cancer who is no longer benefitting from standard anti-cancer treatment or for whom no such treatment is available or indicated.
2. ECOG performance status 0-2
3. Patients must have acceptable organ function as defined below. However, specific inclusion/exclusion criteria specified in the drug-specific study manual will take precedence:
1. Absolute neutrophil count ≥ 1.5 x 109/l
2. Hemoglobin \> 8.0 mmol/l, without blood transfusion within 7 days
3. Platelets \> 75 x 109/l (not applicable for hematological patients)
4. Total bilirubin \< 1.5 x ULN
5. AST and ALT \< 3 x institutional ULN (or \< 5 x ULN in patients with known hepatic metastases)
6. Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 40 mL/min/1.73 m2
4. Patients must have objectively evaluable or measurable disease (by physical or radiographic examination, according to RECIST v1.1, Lugano, IWG and ELN-AML, IMWG, RANO, GCIG, iRESIST or PCWG3.
5. Results must be available from a tumor molecular profiling. Eligible 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) or immunohistochemistry (IHC). The test may have been performed on the primary tumor or a metastatic lesion, in a diagnostic laboratory or within the context of another commercial platform (eg Foundation Medicine), and must reveal a potentially actionable variant.
6. Patients must have a tumor profile for which treatment with one of the approved (or under revision for approval) targeted anti-cancer drugs included in this study has potential clinical benefit based on preclinical data or clinical information.
7. A new (obtained ≤6 months before inclusion after which no further anti-cancer therapy is allowed) fresh frozen and FFPE tumor biopsy specimen or liquid biopsy for extensive biomarker testing is mandatory before the start of treatment with a targeted agent included in the protocol.
8. Ability to understand and the willingness to sign a written informed consent document and comply to the protocol.
9. For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.
10. Because of the risks of drug treatment to the developing fetus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for four months following completion of study therapy. Male patients should avoid impregnating a female partner. Male 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.
Exclusion Criteria:
1. Ongoing toxicity \> grade 2, other than alopecia or \> grade 1 neuropathy.
2. Patient is receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement). Required wash out period prior to starting study treatment is at least two weeks. An exception is made for:
1. Patients suffering from CRPC are allowed to continue androgen deprivation therapy.
2. Medications that are prescribed for supportive care but may potentially have an anti-cancer effect (e.g., megestrol acetate, bisphosphonates). These medications must have been started ≥ 1 week prior to enrollment on this study.
3. Received colony-stimulating factors (eg, G-CSF, GM-CSF or recombinant EPO) within 14 days prior to the first dose of study intervention
4. Patient is pregnant or nursing.
5. Patients with known active progressive brain metastases. Patients with previously treated brain metastases are eligible, provided that the patient is clinically stable and off steroids for at least 4 weeks prior to study initiation. GMB patients apply additional exclusion criteria.
6. Patients with clinically significant preexisting cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure are not eligible.
7. Patients with clinically significant preexisting cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure are not eligible.
8. Patients with known left ventricular ejection fraction (LVEF) \< 45% are not eligible
9. Patients with stroke (including TIA) or acute myocardial infarction within 3 months before the first dose of study treatment are not eligible
10. 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.
For each drug included in this protocol, specific inclusion and exclusion criteria (based on the Package Insert or manufacturers recommendations) may also apply. Drug-specific inclusion and exclusion criteria will take precedence over the inclusion/exclusion criteria listed above.
