Clinical Study to Evaluate Debio0123 + Sacituzumab Govitecan Combination in TNBC or HR+/HER2- Advanced Breast Cancer

NCT06612203 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: MEDOPP0621
• Study Type: interventional
• Target: 76
• Locations: 2 countries
• Sites: 7

Brief Summary

The WIN-B is an international, multicenter, single-arm, phase Ib/II study to evaluate the safety and activity of the Debio 0123 and Sacituzumab govitecan combination therapy in patients with pre-treated advanced/metastatic TNBC or HR+/HER2- breast cancer. Phase Ib will explore if the addition of increasing doses of Debio 0123 to Sacituzumab govitecan is safe and active in pre-treated advanced/metastatic TNBC and HR+/HER2- breast cancer patients. The Debio 0123's recomendad phase 2 doses (RP2D) obtained during phase Ib will then be administered in combination with Sacituzumab govitecan in phase II of the study.

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Phase Ib - Debio 0123's recommended phase II dose (RP2D) when administered in combination with Sacituzumab govitecan in patients with TNBC or HR+/HER2- metastatic breast cancer.

  The RP2D of Debio 0123 when used in combination with Sacituzumab govitecan will be determined based upon evaluation of dose-limiting toxicities (DLTs), adverse events (AEs) and other available data from secondary endpoints.

  Baseline up to 42 days.

• Phase II - Efficacy in terms of objective response rate (ORR) as per RECIST v.1.1 in each cohort.

  ORR, defined as the rate of patients with complete response (CR) or partial response (PR), as determined locally by the investigator using RECIST v.1.1 in patients with TNBC and HR+/HER2- advanced/metastatic breast cancer.

  Approximately 9 months from baseline.

Secondary Outcomes (7)

• Safety and tolerability.

  Approximately 9 months from baseline.

• Preliminary objective response rate (ORR) in TNBC and HR+/HER2- advanced/metastatic breast cancer patients.

  Approximately 9 months from baseline.

• Efficacy in terms of PFS as per RANO-BM for intracranial lesions and RECIST v.1.1 for extracranial lesions in patients with metastatic TNBC and HR+/HER2- advanced/metastatic breast cancer patients.

  Approximately 9 months from baseline.

• Clinical benefit rate (CBR) based on local Investigator assessment as per RANO-BM for intracranial lesions and RECIST v.1.1 for extracranial and overall lesions in TNBC and HR+/HER2- advanced/metastatic breast cancer patients.

  Approximately 9 months from baseline.

• Time to response (TTR) based on local Investigator assessment as per RANO-BM for intracranial lesions and RECIST v.1.1 for extracranial and overall lesions in TNBC and HR+/HER2- advanced/metastatic breast cancer patients.

  Approximately 9 months from baseline.

Study Arms (1)

Debio 0123 + Sacituzumab govitecan

EXPERIMENTAL

Phase Ib of the study will adopt the Bayesian Logistic Regression Model (BLRM) with Overdosing Control. Patients with TNBC and HR+/HER2- advanced/metastatic breast cancer will receive multiple doses of Debio 0123 administered orally during 6 days of each 21-day cycle and 10 mg/kg of Sacituzumab govitecan administered intravenously on D1 and D8 of each 21-day cycle in order to find the RP2D for Debio 0123 when administered in combination with Sacituzumab govitecan. In phase II study, patients with TNBC or HR+/HER2- advanced/metastatic breast cancer will receive the RP2D of Debio 0123 administered orally during 6 days of each 21-day cycle in combination with 10 mg/kg of Sacituzumab govitecan administered intravenously on D1 and D8 of each 21-day cycle until documented disease progression, death, unacceptable toxicity, or discontinuation from the study treatment for any other reason, whichever occurs first.

Drug: Debio 0123 and Sacituzumab govitecan

Interventions

Debio 0123 and Sacituzumab govitecan DRUG

Debio 0123 will be administered orally during 6 days of each 21-day cycle in combination with 10 mg/kg of Sacituzumab govitecan administered intravenously on D1 and D8 of each 21-day cycle until documented disease progression, death, unacceptable toxicity, or discontinuation from the study treatment for any other reason, whichever occurs first.

Also known as: Trodelvy

Debio 0123 + Sacituzumab govitecan

Eligibility Criteria

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

You may qualify if:

• Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
• Female or male patients ≥ 18 years of age at the time of signing ICF.
• Unresectable locally recurrent or metastatic breast cancer documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
• Histologically confirmed TNBC or HR+/HER2- breast cancer as defined by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
• Note: Patients must have known HR and HER2 status locally determined on the most recent analyzed biopsy or FFPE tumor block prior to study entry.
• All patients must have been previously treated with taxanes regardless of disease stage (adjuvant, neoadjuvant, or advanced), unless contraindicated for a given patient.
• Refractory to at least one, and no more than two, prior standard of care chemotherapy regimens for unresectable locally advanced or metastatic breast cancer. Earlier adjuvant or neoadjuvant therapy for more limited disease will be considered as one of the required prior regimens if the development of unresectable locally advanced or metastatic disease occurred within a 12-month period after completion of chemotherapy.
• HR+/HER2- breast cancer patients must be refractory to at least 1 prior anti-cancer hormonal treatment for advanced disease and must have resistance to CDK4/6 inhibitor defined as:
• Disease progression while on, or within 12 months after the end of this treatment in the (neo)adjuvant setting.
• Disease progression to this treatment during advanced disease.
• For phase Ib: evaluable disease according to RECIST v.1.1; for phase II: measurable disease according to RECIST v.1.1.
• Patients with bone-only metastatic disease will be allowed to participate only if they have at least one measurable soft-tissue component ≥10 mm.
• Patients with brain metastasis must have an MRI scan of the brain performed and have had stable CNS disease for at least 4 weeks before entry into the trial.
• Note: low dose corticosteroids for the treatment of brain metastases are permitted provided the dose is stable for 4 weeks.
• Able to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks or fresh tumor biopsy at baseline and after detection of disease progression.

You may not qualify if:

• Current participation in another therapeutic clinical trial, except other translational studies.
• Investigational anti-cancer therapy, chemotherapy or radiotherapy with curative intent within 21 days prior to first dose of study treatment.
• Note: Palliative radiation (e.g., for pain relief) is allowed up to 1 week prior to study treatment start.
• Treatment with monoclonal antibodies/biologics within 28 days prior to first dose of study treatment.
• Has previously been treated with a TROP2-directed antibody-drug conjugate (ADC) or WEE-1 inhibitor in any setting.
• Has previously been treated with topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase 1 inhibitor in any setting.
• Note: for phase Ib, prior treatment with topoisomerase 1 inhibitors or ADC-containing a topoisomerase 1 inhibitor in any setting must be specifically evaluated on a case-by-case basis by the Medical Monitor.
• Patients with advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions \[pleural, pericardial, and/or peritoneal\] and pulmonary lymphangitis).
• Known active uncontrolled or symptomatic central nervous system (CNS) metastases and/or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
• Note: Patients with ≤ 20 mg prednisone or equivalent daily are permitted provided the dose is stable for 4 weeks.
• History of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Has a concurrent malignancy or malignancy within 5 years of study enrollment with the exception of carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.
• Active autoimmune disease that has required systemic treatment in past 2 years or is receiving systemic steroid therapy (e.g., dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment, or any diagnosis of immunodeficiency.
• Known allergy or hypersensitivity reaction to any of the investigational medicinal products (Debio 0123 and Sacituzumab govitecan) or their incorporated substances.
• Major surgical procedure or significant traumatic injury within 14 days before the first dose of study treatment or anticipation of need for major surgery within the course of the study treatment.

Sponsors & Collaborators

• Gilead Sciences: collaborator
• MedSIR: lead
• Debiopharm International SA: collaborator

Study Sites (7)

Hospital Universitari Dexeus

Barcelona, Spain

Location

Hospital Universitario Clínico San Cecilio de Granada

Granada, Spain

Location

Hospital Beata María Ana

Madrid, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital Arnau de Vilanova de Valencia

Valencia, Spain

Location

Beatson West of Scotland Cancer Center

Glasgow, United Kingdom

Location

Barts Health NHS Trust

London, United Kingdom

Location

MeSH Terms

Interventions

sacituzumab govitecan

Study Officials

• Tim Robinson, BMBS, PhD

  University of Bristol, Bristol, England (UK)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 19, 2024
• First Posted: September 25, 2024
• Study Start: January 17, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 5, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5); GB (2)