Study of Lunresertib Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid Tumors (MYTHIC)

Debiopharm

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: Lunresertib; Drug: RP-3500; Drug: Debio0123

Study type: Interventional

Funder types: Industry

Identifiers

NCT04855656

RP-6306-01

Debio 0123-106

Details and patient eligibility

About

The primary purpose of this study is to assess the safety and tolerability of lunresertib 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.

Full description

Phase 1/1b, multi-center, open-label, dose-escalation study to:

• Evaluate the safety profile and MTD of lunresertib 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 lunresertib alone and in combination with RP-3500 or in combination with Debio 0123
• Assess preliminary anti-tumor activity associated with lunresertib alone and in combination with RP-3500 or in combination with Debio 0123

This study was previously posted by Repare Therapeutics. In September 2025, sponsorship of the trial was transferred to Debiopharm International S.A

Enrollment: 464 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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464 participants in 3 patient groups

Phase 1: Lunresertib Single-Agent, Dose Escalation and Food-effect Study

Experimental group

Description:

Patients receive lunresertib orally until disease progression, unacceptable toxicity, or investigator/patient decision. Dose escalation will proceed until a maximum tolerated dose is identified.

Treatment:

Drug: Lunresertib

Phase 1: Lunresertib in combination with RP-3500, Dose Escalation Study

Experimental group

Description:

Patients receive lunresertib with RP-3500 orally until disease progression, unacceptable toxicity, or investigator/patient decision. Dose escalation will proceed until a maximum tolerated dose is identified.

Treatment:

Drug: RP-3500

Drug: Lunresertib

Phase 1: Lunresertib in combination with Debio 0123, Dose Escalation Study

Experimental group

Description:

Patients receive lunresertib with Debio 0123 orally until disease progression, unacceptable toxicity, or investigator/patient decision. Dose escalation will proceed until a maximum tolerated dose is identified.

Treatment:

Drug: Debio0123

Drug: Lunresertib