Phase 1 Study of the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of RP-6306 Alone or in Combination with RP-3500 in Patients with Advanced Solid Tumors (MYTHIC Study)
Trial Description
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.
Eligibility Requirements
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.