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

May 26, 2026 updated by: Debiopharm International SA

Phase 1/1b Study of the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of Lunresertib Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid Tumors

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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

Expanded Access Status: There is no expanded access program available for the investigational products in this study at this time.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
464

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Completed
        • #2002, The Hospital for Sick Children
      • Toronto, Ontario, Canada, M5G 2C1
        • Recruiting
        • #2001, Princess Margaret Cancer Centre
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Completed
        • #2003, The Research Institute of the McGill University Health Centre
  • Denmark
      • Copenhagen, Denmark
        • Recruiting
        • #4001, Rigshospitalet - Blegdamsvej
  • United Kingdom
      • London, United Kingdom, W1G 6AD
        • Recruiting
        • #3003, Sarah Cannon Research Institute
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Completed
        • # 1019, UCLA, Westwood Cancer Center
      • San Francisco, California, United States, 94158
        • Recruiting
        • #1025, University of California San Francisco
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • #1012, Yale
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • #1017, Mayo Clinic
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • #1002, Dana Farber Cancer Institute
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • #1023, START Midwest
    • Minnesota
      • Rochester, Minnesota, United States, 55902
        • Recruiting
        • #1016, Mayo Clinic
    • Missouri
      • St Louis, Missouri, United States, 63130
        • Recruiting
        • #1011, Washington University
    • New York
      • New Hyde Park, New York, United States, 11042
        • Recruiting
        • #1032, Northwell Health Cancer Institute
      • New York, New York, United States, 10065
        • Recruiting
        • #1004, Memorial Sloan Kettering Cancer Institute
      • New York, New York, United States, 10032
        • Completed
        • #1008, Columbia University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Completed
        • #1010, University of Pennsylvania
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • #1007, Rhode Island Hospital
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • #1030, Women & Infants Hospital of Rhode Island
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • #1001, The University of Texas M.D. Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • #1013, The University of Utah
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • #1027, University of Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

8 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Phase 1: Lunresertib Single-Agent, Dose Escalation and Food-effect Study
Patients receive lunresertib orally until disease progression, unacceptable toxicity, or investigator/patient decision. Dose escalation will proceed until a maximum tolerated dose is identified.
Drug: Lunresertib
Oral PKMYT1 Inhibitor
Experimental: Phase 1: Lunresertib in combination with RP-3500, Dose Escalation Study
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.
Drug: RP-3500
Oral ATR Inhibitor
Drug: Lunresertib
Oral PKMYT1 Inhibitor
Experimental: Phase 1: Lunresertib in combination with Debio 0123, Dose Escalation Study
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.
Drug: Debio0123
Oral WEE1 Inhibitor
Drug: Lunresertib
Oral PKMYT1 Inhibitor

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety and Tolerability of lunresertib either in monotherapy or in combination with RP-3500 or with Debio 0123 in patients with eligible advanced solid tumors
Time Frame: Up to 90 days after last administration of study intervention
Assessed by treatment-emergent adverse events (TEAEs), physical examinations (PEs), safety laboratory assessments, electrocardiograms (ECGs), and vital sign measurements
Up to 90 days after last administration of study intervention
To define the MTD of lunresertib monotherapy, and determine a recommended Phase 2 dose (RP2D) and preferred schedule
Time Frame: Up to 90 days after last administration of study intervention
Assessed by the incidence of Dose-limiting toxicities (DLTs) and the incidence and severity of cumulative safety data
Up to 90 days after last administration of study intervention
To define the MTD of lunresertib in combination with RP-3500 or in combination with Debio 0123, and determine a recommended Phase 2 dose (RP2D) and preferred schedule
Time Frame: Up to 90 days after last administration of study intervention
Assessed by the incidence of dose-limiting toxicities (DLTs) and the incidence and severity of cumulative safety data
Up to 90 days after last administration of study intervention
The relative bioavailability of lunresertib capsule formulation as compared to lunresertib tablet formulation in the fasted state
Time Frame: Time 0 (time of dosing) to 72 hours post-dose for each treatment condition
Assessed by the plasma concentrations of lunresertib with calculation of pharmacokinetic (PK) parameters including maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (Tmax), area under the plasma concentration-time curve (AUC) , for both formulations in the fasted state.
Time 0 (time of dosing) to 72 hours post-dose for each treatment condition
The effect of food on the PK of tablet formulation of lunresertib when administered in fed conditions compared to administration under fasted conditions
Time Frame: Time 0 (time of dosing) to 72 hours post-dose for each treatment condition
Assessed by the plasma concentrations of lunresertib with calculation of the ratio of PK parameters (e.g., Cmax and AUC) between the tablet formulation under fasted and fed state.
Time 0 (time of dosing) to 72 hours post-dose for each treatment condition
To assess the safety and tolerability of lunresertib tablets in combination with RP-3500, confirm the MTD of lunresertib tablets in combination with RP-3500, and determine a RP2D and preferred schedule
Time Frame: Up to 90 days after last administration of study intervention
Assessed by DLTs, TEAEs, safety laboratory assessments, the incidence of DLTs and the incidence and severity of cumulative safety data
Up to 90 days after last administration of study intervention

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The plasma concentrations of lunresertib monotherapy (capsule formulation) in the fasted and fed states
Time Frame: Up to 90 days after last administration of study intervention
Assessed by the plasma concentrations of lunresertib with calculation of maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (Tmax), minimum observed plasma concentration (Cmin), area under the plasma concentration-time curve (AUC), elimination half-life (t1/2), and other parameters as appropriate
Up to 90 days after last administration of study intervention
To assess the relationship between pharmacodynamic biomarkers and PK of lunresertib at different dose levels and/or schedules
Time Frame: Up to 90 days after last administration of study intervention
Assessed by evaluation of biomarkers in pre- and on-treatment biopsies, and circulating tumor DNA (ctDNA) dynamics during treatment
Up to 90 days after last administration of study intervention
The plasma concentrations of lunresertib and RP-3500 when dosed in combination
Time Frame: Up to 90 days after last administration of study intervention
Assessed by the plasma concentrations of lunresertib and RP-3500 with calculation of maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (Tmax), minimum observed plasma concentration (Cmin), area under the plasma concentration-time curve (AUC), elimination half-life (t1/2), and other parameters as appropriate for each analyte
Up to 90 days after last administration of study intervention
To assess preliminary anti-tumor activity achieved with lunresertib monotherapy, lunresertib in combination with RP-3500 or lunresertib in combination with Debio 0123
Time Frame: Through Study Completion, an average of 1 year
Measured by best percent change in tumor size from baseline, objective response rate (ORR), overall response rate, tumor marker response, duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS).
Through Study Completion, an average of 1 year
To assess the safety and anti-tumor effects of lunresertib capsule + RP-3500
Time Frame: Through Study Completion, an average of 1 year
As measure by TEAEs, safety laboratory assessments, Best percent change in tumor size from baseline, ORR, overall response rate, DOR, CBR, tumor marker response, PFS
Through Study Completion, an average of 1 year
To further characterize the PK of lunresertib tablets and assess preliminary anti-tumor
Time Frame: Through Study Completion, an average of 1 year
Measured by Plasma concentrations of lunresertib with calculation of Cmax, Tmax, AUC, elimination t1/2, and other PK parameters as appropriate, Best percent change in tumor size from baseline, ORR, overall response rate, DOR, CBR, tumor marker response, PFS
Through Study Completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Debiopharm International SA

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Debiopharm International SA

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 9, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 22, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 28, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Debio 0123-106
  • RP-6306-01 (Other Identifier: Repare Therapeutics)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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