Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer

Inclusion Criteria:

1. Patients must be diagnosed with a solid tumor, CNS tumor or lymphoma that hasprogressed despite standard therapy, or for which no effective standard therapyexists.

2. Age <21 years at inclusion; patients 21 years and older may be included afterapproval by the Study Chair if they have a pediatric type recurrent/refractorymalignancy.

3. Patients must be enrolled on a precision medicine study (i.e. PROFYLE, ZERO orequivalent as agreed with Study Chair).

4. Patients enrolled in a Phase I cohort must have either evaluable or measurabledisease.

5. Patients enrolled in a Phase II cohort must have measurable disease. Evaluable andmeasurable disease are defined by standard imaging criteria for the patient's tumortype.

6. Disease evaluations, laboratory tests, and other clinical assessments that areconsidered standard of care may be undertaken at the patient's local oncologytreatment centre with results transferred to study site for evaluation.

7. Performance status: Karnofsky performance status (for patients > 16 years of age) orLansky play score (for patients ≤ 16 years of age) ≥ 50%.

8. Life expectancy ≥ 6 weeks.

9. Patients must have fully recovered from the acute toxic effects of all prioranticancer therapy and must meet the following minimum duration from prioranticancer-directed therapy prior to enrolment.

10. Adequate organ function.

11. Able to comply with scheduled follow-up and with management of toxicity.

12. Females of childbearing potential must have a negative serum or urine pregnancytest.

13. Fertile males must agree to use adequate contraception during the study andfollowing completion of treatment.

14. Provide a signed and dated informed consent form.

Exclusion Criteria:

1. Patients with symptomatic central nervous system (CNS) primary or metastatic tumourswho are neurologically unstable or require increasing doses of corticosteroids orlocal CNS-directed therapy to control their CNS disease. Patients on stable doses ofcorticosteroids for at least 7 days prior to receiving study drug may be included.

2. Impairment of gastrointestinal (GI) function or GI disease that may significantlyalter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea,vomiting, diarrhoea, or malabsorption syndrome) - only for arms that include orallyadministered therapeutic agents.

3. Clinically significant, uncontrolled heart disease (including history of any cardiacarrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conductionabnormality), unstable ischemia, congestive heart failure within 12 months ofscreening.

4. Known active viral hepatitis or human immunodeficiency virus (HIV) infection or anyother uncontrolled infection.

5. Major surgery within 21 days of the first dose of investigational drug. Gastrostomy,ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumour biopsy and insertionof central venous access devices are not considered major surgery, but for theseprocedures, a 48-hour interval must be maintained before the first dose of theinvestigational drug is administered.

6. Known hypersensitivity to any study drug or component of the formulation.

7. Pregnant or nursing (lactating) females.

8. Any other concomitant serious medical condition or organ dysfunction that in theopinion of the investigator would either compromise patient safety or interfere withthe evaluation of the safety of the investigational drug(s).