Study of RP-6306 Alone or in Combination with RP-3500 or Debio 0123 in Patients with Advanced Solid Tumors

Inclusion Criteria:

• Male or female and ≥12 years-of-age at the time of informed consent.

• Lansky performance status ≥50% for patients ≤16 years of age, or ECOG score of 0, 1, (or 2 for module 1) for patients >16 years of age.

• Locally advanced or metastatic resistant or refractory solid tumors.

• Patients <18 years of age must weigh at least 40 kg.

• Submission of available tumor tissue at screening or willingness to have a biopsyperformed if safe and feasible

• Next generation sequencing (NGS) report obtained in a CLIA-certified or equivalentlaboratory demonstrating eligible tumor biomarker.

• CCNE1 amplification (non-equivocal) as determined by either a tumor or plasma NGStest, or FISH

• FBXW7 deleterious mutations identified by either a tumor or plasma NGS test

• PPP2R1A deleterious mutations identified by either a tumor or plasma NGS test

• Measurable disease as per RECIST v1.1. For certain modules, patients with prostatecancer or ovarian cancer that have non-measurable disease but have elevated tumormarkers (PSA or CA-125, respectively) can also be eligible

• Ability to swallow and retain oral medications.

• Acceptable hematologic and organ function at screening.

• Negative pregnancy test (serum) for women of childbearing potential (WOCBP) atScreening.

• Resolution of all toxicities of prior therapy or surgical procedures.

• Any prior radiation must have been completed at least 7 days prior to the start ofstudy drugs, and patients must have recovered from any acute adverse effects priorto the start of study treatment.

Exclusion Criteria:

• Chemotherapy or small molecule antineoplastic agent given within 21 days or <5half-lives, whichever is shorter, prior to first dose of study drug.

• History or current condition, therapy, or laboratory abnormality that might confoundthe study results or interfere with the patient's participation for the fullduration of the study treatment.

• Patients who are pregnant or breastfeeding.

• Life-threatening illness, medical condition, active uncontrolled infection, or organsystem dysfunction or other reasons which, in the investigator's opinion, couldcompromise the participating patient's safety.

• Major surgery within 4 weeks prior to first dose of RP-6306.

• Uncontrolled, symptomatic brain metastases.

• Uncontrolled hypertension.

• Certain prior anti-cancer therapy

• Psychological, familial, sociological, or geographical conditions that do not permitcompliance with the protocol and/or follow-up procedures outlined in the protocol.