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

Eligibility 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 biopsy performed if safe and feasible
• * Next generation sequencing (NGS) report obtained in a CLIA-certified or equivalent laboratory demonstrating eligible tumor biomarker.
• * CCNE1 amplification (non-equivocal) as determined by either a tumor or plasma NGS test, 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 prostate cancer or ovarian cancer that have non-measurable disease but have elevated tumor markers (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) at Screening.
• * 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 of study drugs, and patients must have recovered from any acute adverse effects prior to the start of study treatment.
• * Chemotherapy or small molecule antineoplastic agent given within 21 days or \<5 half-lives, whichever is shorter, prior to first dose of study drug.
• * History or current condition, therapy, or laboratory abnormality that might confound the study results or interfere with the patient's participation for the full duration of the study treatment.
• * Patients who are pregnant or breastfeeding.
• * Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction or other reasons which, in the investigator's opinion, could compromise 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 permit compliance with the protocol and/or follow-up procedures outlined in the protocol.