study of rp-6306 alone or in combination with rp-3500 or debio 0123 in patients with advanced solid tumors

Conditions: Advanced Solid Tumor

Summary: the primary purpose of this study is to assess the safety and tolerability of rp-6306 alone and in combination with rp-3500 or in combination with debio 0123 in patients with eligible advanced solid tumors, determine the maximum tolerated dose (mtd) and assess preliminary anti-tumor activity.

phase 1/1b, multi-center, open-label, dose-escalation study to: * evaluate the safety profile and mtd of rp-6306 alone and in combination with rp-3500 or in combination with debio 0123 when administered orally to establish the recommended phase 2 dose and schedule * characterize the pk and pharmacodynamics of rp-6306 alone and in combination with rp-3500 or in combination with debio 0123 * assess preliminary anti-tumor activity associated with rp-6306 alone and in combination with rp-3500 or in combination with debio 0123

Eligibility criteria:
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 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.