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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05109975
• Other study ID #: Debio 0123-102
• Status: Recruiting
• Phase: Phase 1
• Start date: November 5, 2021
• Est. completion date: June 2027

Study information

• Verified date: March 2024
• Source: Debiopharm International SA
• Contact: Debiopharm International S.A
• Phone: +41 21 321 01 11
• Email: clinicaltrials[@]debiopharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 155
• Est. completion date: June 2027
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.]

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• Debio 0123
Debio 0123 orally during 21-day treatment cycles.

Locations

Country	Name	City	State
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Institut Catala de Oncologia	Girona
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	START Madrid. Hospital Fundación Jimenez Diaz	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
Switzerland	Istituto Oncologico della Svizzera italiana - Ente Ospedaliero Cantonale	Bellinzona
Switzerland	Universitätsspital Zürich, Dermatologische Klinik	Zürich
United States	South Texas Accelerated Research Therapeutics (START) Midwest	Grand Rapids	Michigan
United States	South Texas Accelerated Research Therapeutics (START)	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Countries where clinical trial is conducted

United States,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Maximum Tolerated Dose (MTD) as Determined by Percentage of Participants with Dose Limiting Toxicities (DLTs)		Cycle 1 (each cycle is 21 days)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	Part 2: Overall Response Rate (ORR)		From the start of study treatment until disease progression (up to 12 months)
Secondary	Part 1: Percentage of Participants with SAEs		Up to 30 days after the last dose of study treatment (up to 13 months)
Secondary	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)
Secondary	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)
Secondary	Parts 1 and 2: Anti-Tumor Activity as Assessed by Percentage of Participants with Tumor Response		Parts 1 and 2: Up to 12 months