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

NCT04855656 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: Debio 0123-106RP-6306-01
• Study Type: interventional
• Target: 464
• Locations: 4 countries
• Sites: 22

Brief Summary

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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (6)

• 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

  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

  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

  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

  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

  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

  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 Outcomes (6)

• The plasma concentrations of lunresertib monotherapy (capsule formulation) in the fasted and fed states

  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

  Up to 90 days after last administration of study intervention

• The plasma concentrations of lunresertib and RP-3500 when dosed in combination

  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

  Through Study Completion, an average of 1 year

• To assess the safety and anti-tumor effects of lunresertib capsule + RP-3500

  Through Study Completion, an average of 1 year

Study Arms (3)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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: Lunresertib; Drug: RP-3500

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

EXPERIMENTAL

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: Lunresertib; Drug: Debio0123

Interventions

Lunresertib DRUG

Oral PKMYT1 Inhibitor

Phase 1: Lunresertib Single-Agent, Dose Escalation and Food-effect Study; Phase 1: Lunresertib in combination with Debio 0123, Dose Escalation Study; Phase 1: Lunresertib in combination with RP-3500, Dose Escalation Study

RP-3500 DRUG

Oral ATR Inhibitor

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

Debio0123 DRUG

Oral WEE1 Inhibitor

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

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (22)

# 1019, UCLA, Westwood Cancer Center

Los Angeles, California, 90095, United States

COMPLETED

#1025, University of California San Francisco

San Francisco, California, 94158, United States

RECRUITING

#1012, Yale

New Haven, Connecticut, 06520, United States

RECRUITING

#1017, Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

#1002, Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

#1023, START Midwest

Grand Rapids, Michigan, 49503, United States

RECRUITING

#1016, Mayo Clinic

Rochester, Minnesota, 55902, United States

RECRUITING

#1011, Washington University

St Louis, Missouri, 63130, United States

RECRUITING

#1032, Northwell Health Cancer Institute

New Hyde Park, New York, 11042, United States

RECRUITING

#1008, Columbia University

New York, New York, 10032, United States

COMPLETED

#1004, Memorial Sloan Kettering Cancer Institute

New York, New York, 10065, United States

RECRUITING

#1010, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

COMPLETED

#1007, Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

#1030, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02903, United States

RECRUITING

#1001, The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

#1013, The University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

#1027, University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

#2002, The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

COMPLETED

#2001, Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C1, Canada

RECRUITING

#2003, The Research Institute of the McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

COMPLETED

#4001, Rigshospitalet - Blegdamsvej

Copenhagen, Denmark

RECRUITING

#3003, Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

RECRUITING

Central Study Contacts

Debiopharm International S.A

CONTACT

+41 21 321 01 11; clinicaltrials@debiopharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2021
• First Posted: April 22, 2021
• Study Start: April 30, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (17); CA (3); DK (1); GB (1)