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)

Protocol # :
Advanced Solid Tumor
Disease Sites
Healthy volunteer
Transplanted organ and tissue status, unspecified
Disease not specified
Gastroesophageal Junction
Other specified personal risk factors, not elsewhere classified
Lip, Oral Cavity and Pharynx
Small Intestine
Other Digestive Organ
Other Respiratory and Intrathoracic Organs
Bones and Joints
Soft Tissue
Mycosis Fungoides
Other Skin
Corpus Uteri
Other Female Genital
Other Male Genital
Urinary Bladder
Other Urinary
Eye and Orbit
Brain and Nervous System
Unknown Sites
Ill-Defined Sites
Other Endocrine System
Kaposi's Sarcoma
Melanoma, Skin
Principal Investigator
Lee, Elizabeth

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

- 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.