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

• ClinicalTrials.gov Identifier: NCT05109975
• Recruitment Status: Recruiting
• First Posted: November 5, 2021
• Last Update Posted: March 29, 2024
• Sponsor: Debiopharm International SA
• Information provided by (Responsible Party): Debiopharm International SA

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors	Drug: Debio 0123	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 155 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 5, 2021
• Estimated Primary Completion Date: January 2026
• Estimated Study Completion Date: June 2027

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Part 1: Maximum Tolerated Dose (MTD) as Determined by Percentage of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (each cycle is 21 days) ]
2. Part 1: Recommended Phase 2 Dose (RP2D) as Determined by Percentage of Participants with DLTs and Cumulative Safety Data [ Time Frame: Cycle 1 (each cycle is 21 days) ]
3. Part 2: Percentage of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to 30 days after the last dose of study treatment (up to 13 months) ]
4. Part 2: Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) and Laboratory Abnormalities [ Time Frame: Up to 30 days after the last dose of study treatment (up to 13 months) ]
5. Part 2: Percentage of Participants with Treatment Discontinuations and Treatment Modifications due to Adverse Events (AEs) and Laboratory Abnormalities [ Time Frame: Up to end of study treatment (up to 12 months) ]
6. Part 2: Overall Response Rate (ORR) [ Time Frame: From the start of study treatment until disease progression (up to 12 months) ]

Secondary Outcome Measures :

1. Part 1: Percentage of Participants with SAEs [ Time Frame: Up to 30 days after the last dose of study treatment (up to 13 months) ]
2. Part 1: Percentage of Participants with TEAEs and Laboratory Abnormalities [ Time Frame: Up to 30 days after the last dose of study treatment (up to 13 months) ]
3. Part 1: Plasma Concentration of Debio 0123 [ Time Frame: 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) ]
   The pharmacokinetics (PK) of Debio-0123 will be evaluated in plasma.
4. Parts 1 and 2: Anti-Tumor Activity as Assessed by Percentage of Participants with Tumor Response [ Time Frame: Parts 1 and 2: Up to 12 months ]

Eligibility Criteria

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

Criteria

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.]

Contacts and Locations

Contacts

Contact: Debiopharm International S.A; +41 21 321 01 11; clinicaltrials@debiopharm.com

Locations

United States, Michigan

South Texas Accelerated Research Therapeutics (START) Midwest; Recruiting

Grand Rapids, Michigan, United States, 49546

United States, Texas

South Texas Accelerated Research Therapeutics (START); Recruiting

San Antonio, Texas, United States, 78229

Spain

Hospital Universitari Vall d'Hebron; Not yet recruiting

Barcelona, Spain, 08035

Institut Catala de Oncologia; Not yet recruiting

Girona, Spain, 17007

Clinica Universidad de Navarra; Not yet recruiting

Madrid, Spain, 28027

START Madrid. Hospital Fundación Jimenez Diaz; Not yet recruiting

Madrid, Spain, 28040

Hospital Universitario 12 de Octubre; Not yet recruiting

Madrid, Spain, 28041

Hospital Universitario La Paz; Not yet recruiting

Madrid, Spain, 28046

Clinica Universidad de Navarra; Not yet recruiting

Pamplona, Spain, 31008

Switzerland

Istituto Oncologico della Svizzera italiana - Ente Ospedaliero Cantonale; Not yet recruiting

Bellinzona, Switzerland, 6500

Universitätsspital Zürich, Dermatologische Klinik; Completed

Zürich, Switzerland, 8058

Sponsors and Collaborators

Debiopharm International SA

More Information

• Responsible Party: Debiopharm International SA
• ClinicalTrials.gov Identifier: NCT05109975
• Other Study ID Numbers: Debio 0123-102
• First Posted: November 5, 2021
• Last Update Posted: March 29, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Debiopharm International SA:

Advanced Solid Tumors; WEE1-inhibitor

Additional relevant MeSH terms:

Neoplasms