Study of Efficacy and Safety of Ribociclib (LEE011) in Combination With Topotecan and Temozolomide (TOTEM) in Pediatric Patients With Relapsed or Refractory Neuroblastoma and Other Solid Tumors

Inclusion Criteria:

1. Participants and/or guardian have the ability to understand and the willingness tosign a written informed consent document.

2. Age ≥ 12 months and ≤ 21 years at the time of signing consent form Note: The firstdose level of Phase I - part A (dose finding) will enroll participants ≥ 12 years - 21 years old, and may expand to younger participants (≥ 12 months to < 12 years) asdetermined by the data.

3. Histologically or cytologically confirmed solid tumors listed below that haveprogressed despite standard therapy or for which no effective standard therapyexists.

4. Neuroblastoma (for Phase I and Phase II): Histologically proven neuroblastomaas per International Neuroblastoma Staging System (INSS); Relapsed orrefractory disease; Measurable disease per International Neuroblastoma Responsecriteria (INRC); Bone marrow only disease not eligible; Available MYCN statusbefore screening

5. Medulloblastoma (for Phase I) regardless of genetic status (i.e. Groups 3 or 4WNT-activated or non-WNT, SHH-activated or non-SHH)

6. High-grade glioma (for Phase I): including HGG NOS, WHO Grade III or Grade IV;Glioblastoma, IDH-wildtype or IDH-mutant; Anaplastic astrocytoma, IDH-mutant;Anaplastic oligodendroglioma, IDH-mutant; Anaplastic pleomorphicxanthoastrocytoma; Diffuse midline gliomas, H3 K27-altered; Diffuse hemisphericglioma, H3 G34-mutant; Diffuse pediatric-type HGG, H3-wildtype andIDH-wildtype.

7. Malignant rhabdoid tumor (for Phase I) includes diagnoses of atypicalteratoid/rhabdoid tumor (AT/RT), and rhabdoid tumor of the kidney (RTK), andother soft tissues as defined by 2 of the 3 following criteria; either (1)+(2)or (1)+(3): (1) Morphology and immunophenotypic panel consistent with rhabdoidtumor; (2) Loss of SMARCB1 confirmed by immunohistochemistry; (3) Molecularconfirmation of tumor-specific bi-allelic SMARCB1 loss/mutation is encouragedin cases where SMARCB1 immunohistochemistry is equivocal, and required ifSMARCB1 immunohistochemistry is not available

8. Rhabdomyosarcoma (for Phase I) independent of fusion status and subtype

9. Participants with CNS disease who are on corticosteroids should take stable dosesfor at least 7 days prior to first dose of ribociclib with no plans for escalation.

10. Performance status:

11. ≤ 16 years: Lansky Play score ≥ 50%

12. >16 years: Karnofsky performance status ≥ 50% or ECOG < 3

13. Life expectancy of ≥ 12 weeks at the time of enrollment

14. Adequate bone marrow function (bone marrow may be involved with tumor) and organfunction

15. Adequate hepatic, renal, cardiac function

16. Females who are sexually active must agree to use highly effective contraceptionduring and for 6 months after treatment. Additionally, females of childbearingpotential must have a negative serum pregnancy test within 7 days prior to the firstdose of study medication. Pregnant or lactating females are not eligible for thestudy.

17. Sexually active males (including those that have had a vasectomy), who do not agreeto abstinence, must be willing to use a condom during intercourse while on studytreatment and for 6 months after stopping treatment.

Exclusion Criteria:

1. Known hypersensitivity to any of the excipients of ribociclib or topotecan ortemozolomide.

2. Not recovered from clinical and laboratory acute toxicities related to prioranti-cancer therapies

3. Concurrent severe and/or uncontrolled concurrent medical conditions (seriousinfections or significant cardiac, pulmonary, hepatic, psychiatric, GI disease, orother organ dysfunction) that in the investigator's judgement could compromise theirability to tolerate or absorb protocol therapy or would interfere with the studyprocedures or results

4. Clinically significant, uncontrolled heart disease and/or cardiac repolarizationabnormality

5. History of QTc prolongation; taking medications with a known risk to prolong the QTinterval hat cannot be discontinued or replaced by safe alternative medication

6. Currently taking medications that are mainly metabolized by CYP3A4/5 with a narrowtherapeutic index, strong inducers or inhibitors of CYP3A4/5, herbalpreparations/medications and dietary supplements

7. Vaccinated with live, attenuated vaccines within 4 weeks

8. Participated in a prior investigational study within 30 days

9. Received prior treatment with a CDK4/6 inhibitor

10. Received last dose of anticancer therapy (including experimental) within 4 weeks

11. Previous myeloablative therapy with autologous hematopoietic stem cell rescue within 8 weeks

12. Allogeneic stem cell transplant within 3 months

13. Has last fraction of radiation within 4 weeks

14. Major surgery within 2 weeks

15. Pregnant or nursing (breast feeding) female participant or female participant whoplans to become pregnant or breast-feed during the trial.

Other protocol-defined inclusion/exclusion criteria may apply