A Study to Evaluate Safety and Preliminary Anti-tumor Activity of Debio 0123 as Monotherapy in Adult Participants With Advanced Solid Tumors

NCT05109975 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: Debio 0123-1022023-504824-24
• Study Type: interventional
• Target: 66
• Locations: 3 countries
• Sites: 15

Brief Summary

This study has two parts: Part 1 and Part 2. The purpose of this study in Part 1, Dose Escalation Part is to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of Debio 0123 as monotherapy with repeated dosing in adults with advanced solid tumors that recurred or progressed after prior therapy and/or for whom no standard therapy of proven benefit is available. The purpose in Part 2, Expansion Part of this study, is to characterize the safety and tolerability of Debio 0123 in each study arm and overall when administered as monotherapy at the MTD/RP2D determined during the Dose Escalation Part 1 and to evaluate the preliminary anti-tumor activity of Debio 0123 when administered as monotherapy to participants in each study arm.

Conditions

Advanced Solid Tumors

Keywords

Advanced Solid Tumors; WEE1-inhibitor

Outcome Measures

Primary Outcomes (6)

• Part 1: Maximum Tolerated Dose (MTD) as Determined by Percentage of Participants with Dose Limiting Toxicities (DLTs)

  Cycle 1 (each cycle is 21 days)

• Part 1: Recommended Phase 2 Dose (RP2D) as Determined by Percentage of Participants with DLTs and Cumulative Safety Data

  Cycle 1 (each cycle is 21 days)

• Part 2: Percentage of Participants with Serious Adverse Events (SAEs)

  Up to 30 days after the last dose of study treatment (up to 13 months)

• Part 2: Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) and Laboratory Abnormalities

  Up to 30 days after the last dose of study treatment (up to 13 months)

• Part 2: Percentage of Participants with Treatment Discontinuations and Treatment Modifications due to Adverse Events (AEs) and Laboratory Abnormalities

  Up to end of study treatment (up to 12 months)

• Part 2: Overall Response Rate (ORR)

  From the start of study treatment until disease progression (up to 12 months)

Secondary Outcomes (4)

• Part 1: Percentage of Participants with SAEs

  Up to 30 days after the last dose of study treatment (up to 13 months)

• Part 1: Percentage of Participants with TEAEs and Laboratory Abnormalities

  Up to 30 days after the last dose of study treatment (up to 13 months)

• Part 1: Plasma Concentration of Debio 0123

  Pre-dose and at multiple time points up to 8 hours (h) on Day 1, Cycle 1 in Part 1 and 4 h on Day 1, Cycle 1 in Part 2 (each cycle is 21 days)

• Parts 1 and 2: Anti-Tumor Activity as Assessed by Percentage of Participants with Tumor Response

  Parts 1 and 2: Up to 12 months

Study Arms (2)

Part 1: Dose Escalation

EXPERIMENTAL

Participants will receive Debio 0123 orally in escalating dose cohorts during each 21-day treatment cycle until progression of disease, unacceptable toxicity, participant's withdrawal, or Investigator's decision, whichever occurs first.

Drug: Debio 0123

Part 2: Expansion

EXPERIMENTAL

Debio 0123 at the RP2D established in Part 1 participants with uterine serous carcinoma (USC) (arm A), recurrent or progressive, high-grade epithelial ovarian cancer (EOC) with cyclin E1 (arm B), and solid tumor with biomarker-driven selection (arm C).

Drug: Debio 0123

Interventions

Debio 0123 DRUG

Debio 0123 orally during 21-day treatment cycles.

Part 1: Dose Escalation; Part 2: Expansion

Eligibility Criteria

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

You may qualify if:

• Part 1 dose escalation only:
• Histologically or cytologically confirmed locally advanced or metastatic solid tumors.
• Measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
• Disease progression under or following standard therapy and/or disease for which no available standard therapy of proven benefit.
• Part 2 expansion only:
• Measurable disease per RECIST version 1.1 criteria for each arm.
• Participants (≥18 years old) who progressed or have recurrence of one of the tumor types specified in the study arms following standard therapy according to RECIST version 1.1, or for whom, in the opinion of the Investigator, no effective standard therapy exists.
• Arm A: Histologically or cytologically confirmed USC that recurred or progressed following at least 1 prior platinum-based line of therapy for management of advanced or metastatic disease.
• Arm B: Histologically or cytologically confirmed, recurrent, high-grade EOC, primary peritoneal cancer, or fallopian tube cancer with cyclin E1 driven selection. Participants must have progressed after at least 1 prior platinum-based therapy for advanced/metastatic disease.
• Arm C: Histologically or cytologically confirmed, locally advanced or metastatic solid tumor with biomarker-driven selection.
• Part 1 dose escalation and Part 2 expansion:
• Accessible tumor for biopsy, and participant willing to undergo tumor biopsy unless archived tumor sample is available.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• Life expectancy of at least 3 months, in the best judgment of the Investigator.
• Adequate bone marrow, liver biochemistry, renal function, and coagulation status.

You may not qualify if:

• Participants with active second malignancies requiring therapy in the last 6 months, with the exception of superficial bladder cancers, ductal carcinoma in situ or other carcinomas in situ, and non-melanoma non-melanoma skin cancers (basal cell/squamous cell skin cancer) that have been treated surgically.
• Current use of an investigational agent or a medical device.
• Major surgery ≤4 weeks prior to the first dose of study treatment or who have not recovered from the surgical procedure.
• History of myocardial infarction or stroke within 6 months, congestive heart failure greater than New York Heart Association (NYHA) class II, unstable angina pectoris, unexplained recurrent syncope, cardiac arrhythmia requiring treatment, family history of sudden death from cardiac-related causes before the age of 50, or any cardiotoxicity experienced after previous chemotherapy.
• Known infection requiring systemic use of an antibiotic or antiviral agent.
• Pregnancy or breast-feeding.
• Inability or unwillingness to swallow oral medication.
• Clinically significant gastrointestinal abnormality that would affect the absorption of the drug.
• Any anti-cancer treatment, monoclonal antibodies/biologics, investigational treatment, or radiotherapy with curative intent within 28 days prior to starting study treatment. Palliative radiation for pain relief is allowed up to 1 week prior to starting study treatment.
• Unresolved AEs or toxicities due to previous treatments, i.e., \>Grade 1. Exceptions will be made for Grade 2 anemia (if hemoglobin is not less than 9 g/dL or 5.6 mmol/L) and \>Grade 2 alopecia and endocrinopathies controlled by replacement therapy (example, hypothyroidism due to immune checkpoint inhibitors).

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (15)

South Texas Accelerated Research Therapeutics (START) Midwest

Grand Rapids, Michigan, 49546, United States

Location

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

Location

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Institut Catala de Oncologia

Girona, 17007, Spain

Location

Clinica Universidad de Navarra

Madrid, 28027, Spain

Location

START Madrid. Hospital Fundación Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Istituto Oncologico della Svizzera italiana - Ente Ospedaliero Cantonale

Bellinzona, 6500, Switzerland

Location

Kantonsspital St. Gallen, Rorschacher Strasse 95

Sankt Gallen, 9007, Switzerland

Location

Universitätsspital Zürich, Dermatologische Klinik

Zurich, 8058, Switzerland

Location

Study Design

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

Study Record Dates

• First Submitted: October 26, 2021
• First Posted: November 5, 2021
• Study Start: November 5, 2021
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); ES (8); CH (3)