Study of Lunresertib 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 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.

Exclusion Criteria

• 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 lunresertib.
• 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.