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

A Phase 1, Dose-finding Study of Debio 0123 as Monotherapy in Adult Patients With Advanced Solid Tumors, Followed by an Expansion Part to Assess Safety and Preliminary Anti-tumor Activity

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Debio 0123

• Study Type: Interventional
• Enrollment (Estimated): 155
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Debiopharm International S.A; Phone Number: +41 21 321 01 11; Email: clinicaltrials@debiopharm.com

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Not yet recruiting
    • Hospital Universitari Vall d'Hebron
  • Girona, Spain, 17007
    • Not yet recruiting
    • Institut Catala de Oncologia
  • Madrid, Spain, 28046
    • Not yet recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28027
    • Not yet recruiting
    • Clinica Universidad de Navarra
  • Madrid, Spain, 28041
    • Not yet recruiting
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28040
    • Not yet recruiting
    • START Madrid. Hospital Fundación Jimenez Diaz
  • Pamplona, Spain, 31008
    • Not yet recruiting
    • Clinica Universidad de Navarra
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Not yet recruiting
    • Istituto Oncologico della Svizzera italiana - Ente Ospedaliero Cantonale
  • Zürich, Switzerland, 8058
    • Completed
    • Universitätsspital Zürich, Dermatologische Klinik
• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • South Texas Accelerated Research Therapeutics (START) Midwest
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • South Texas Accelerated Research Therapeutics (START)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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. 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, specific solid tumors.

• 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.
  • Willing to practice highly effective methods of contraception.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

• 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.
• Brain tumors and/or brain metastases unless they are asymptomatic, stable on recent imaging (not dated more than 28 days from the inclusion date), and have not required active treatment in the last month before study entry.
• 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, or any cardiotoxicity experienced after previous chemotherapy.
• Known infection requiring systemic use of an antibiotic or antiviral agent.
• Immunization with live or live-attenuated vaccine within 28 days prior to study inclusion or planned injection of live or live-attenuated vaccines.
• Pregnancy or breast-feeding.
• Inability or unwillingness to swallow oral medication.
• Clinically significant gastrointestinal abnormality that would affect the absorption of the drug.
• Chemotherapy, monoclonal antibodies/biologics, 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).

[Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.]

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation; 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; Debio 0123 orally during 21-day treatment cycles.
Experimental: Part 2: Expansion; 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-driven selection (arm B), and solid tumor with biomarker-driven selection (arm C).	Drug: Debio 0123; Debio 0123 orally during 21-day treatment cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 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)
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Parts 1 and 2: Anti-Tumor Activity as Assessed by Percentage of Participants with Tumor Response		Parts 1 and 2: Up to 12 months
Part 1: Plasma Concentration of Debio 0123	The pharmacokinetics (PK) of Debio-0123 will be evaluated in plasma.	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)

Collaborators and Investigators

• Sponsor: Debiopharm International SA

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2021
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: October 26, 2021
• First Submitted That Met QC Criteria: October 26, 2021
• First Posted (Actual): November 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Advanced Solid Tumors; WEE1-inhibitor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: Debio 0123-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No