A phase 2, interventional, nonrandomized, parallel treatment assignment, open label trial

Patients will be discussed within a tumor board (medical oncology) prior to inclusion.

Patients (if deemed eligible) can be treated with:

• Panitumumab
• Olaparib
• Dabrafenib
• Nilotinib
• Trametinib
• Erlotinib
• Trastuzumab and Pertuzumab (combination treatment)
• Vemurafenib and Cobimetinib (combination treatment)
• Vismodegib
• Regorafenib
• Nivolumab

Percentage of submitted patients, ORR, safety.

Adult (age >18 years) patient with a histologically¬ proven locally advanced or metastatic solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma who is no longer benefitting from standard anticancer treatment or for whom no such treatment is available or indicated.

ECOG performance status 0¬2.

Patients must have acceptable organ function as defined below. However, specific inclusion/ exclusion criteria specified in the drug-specific study manual will take precedence: Absolute neutrophil count ≥ 1.5 x 109/l, Hemoglobin > 5.6 mmol/l, Platelets > 75 x 109/l, Total bilirubin

< 2 x ULN, AST (SGOT) and ALT (SGPT) < 2.5 x institutional ULN (or < 5 x ULN in patients with known hepatic metastases), Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 50 mL/min/1.73 m2.

Patients must have objectively evaluable or measurable disease.

Results must be available from a tumor genomic or protein expression test.

Patients must have a tumor profile for which single agent treatment with one of the EMA approved targeted anti- cancer drugs included in this study has potential clinical benefit based on preclinical data or clinical information (see section 5).

A new (obtained ≤2 months before inclusion, and without any type of anti-cancer therapy within those ≤2 months ) fresh frozen tumor biopsy specimen for extensive biomarker testing is mandatory before the start of treatment with a targeted agent included in the protocol.

Ability to understand and the willingness to sign a written informed consent document.

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 childbearing 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.

Ongoing toxicity > grade 2, other than alopecia.

Patient is receiving any other anticancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) except for medications that are prescribed for supportive care but may potentially have an anticancer effect (e.g., megestrol acetate, bisphosphonates). These medications must have been started ≥ 1 week prior to enrollment on this study.

Patient is pregnant or nursing.

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 the 3 months prior to registration. All patients with previously treated brain metastases must be stable for at least 1 month after completion of treatment and off steroid treatment prior to study enrollment.

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.

Patients with known left ventricular ejection fraction (LVEF) < 40% are not eligible.

Patients with stroke (including TIA) or acute myocardial infarction within 3 months before the first dose of study treatment are not eligible.

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.