Testing Two Different Drugs (Sacituzumab-govitecan and Trastuzumab-deruxtecan) Combinations Prescribed in an Alterning Pattern to Patients With Metastatic or Locally Advanced Triple-negative Breast Cancer

NCT07151586 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: UC-BCG-25032025-521909-40-00
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase II, multicentre, open-label, randomised controlled trial (patients are randomly assigned to one treatment arm or the other) evaluating two treatment strategies (sacituzumab govitecan and trastuzumab deruxtecan in an alternative schema or sacituzumab govitecan alone) in patients with locally advanced or metastatic triple-negative breast cancer. The goal is to answer the question: Does alternating sacituzumab goveitecan (SG) and trastuzumab deruxtecan (T-DXd) improve survival in patients with HER2-low metastatic triple-negative breast cancer compared to continuing treatment with SG alone?

Conditions

Triple Negative Breast Neoplasms; Neoplasm Metastasis; HER 2 Low-expressing Breast Cancer

Keywords

Antibody-drug conjugates; HER2-low; Triple Negative Breast Cancer; Locally Advanced Breast Cancer; HER2-negative; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  The overall survival is the length of time from randomization that patients enrolled in the study are still alive

  From randomization to death from any cause, up to 4 years.

Secondary Outcomes (6)

• Clinical Benefit Rate (CBR)

  Time from randomization to disease progression, up to 4 years.

• Objective response rate (ORR)

  Time from randomization to disease progression, up to 4 years.

• Progression-free survival (PFS),

  From randomization to disease progression or death, up to 4 years.

• Quality-Adjusted progression free survival (QA-PFS)

  From randomization to disease progression or death, up to 4 years.

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  From first dose through 30 days after the last dose of study treatment

Study Arms (2)

Sacituzumab-Govitecan and Trastuzumab-deruxtecan in alternating shema

EXPERIMENTAL

Patients will receive either SG and T-DXd in an upfront alternating schema: two cycles of SG, followed by two cycles of T-DXd, then two cycles of SG, and so on, until RECIST 1.1-defined disease progression, unless there is unacceptable toxicity, withdrawal of consent or end of study.

Drug: Sacituzumab Govitecan / Trastuzumab Deruxtecan

Sacituzumab-Govitecan alone

ACTIVE COMPARATOR

Patient will receive Sacituzumab-Govitecan 1(monotherapy) until RECIST 1.1-defined disease progression, unless there is unacceptable toxicity, withdrawal of consent or end of study

Drug: Sacituzumab Govitecan / Trastuzumab Deruxtecan

Interventions

Sacituzumab Govitecan / Trastuzumab Deruxtecan DRUG

Sacituzumab govitecan is administered intravenously at a dose of 10 mg/kg on Day 1 and Day 8 of each 3-week cycle. In this study, patients receive two cycles of sacituzumab govitecan followed by two cycles of trastuzumab deruxtecan, alternating throughout the study. Trastuzumab deruxtecan is administered intravenously at a dose of 5.4 mg/kg on Day 1 of each 3-week cycle. In this study, patients receive two cycles of trastuzumab deruxtecan followed by two cycles of sacituzumab govitecan, alternating throughout the study. Both Treatment are continued until disease progression as defined by RECIST 1.1, unacceptable toxicity, withdrawal of consent, or the end of the study.

Also known as: Trodelvy, Enhertu

Sacituzumab-Govitecan alone; Sacituzumab-Govitecan and Trastuzumab-deruxtecan in alternating shema

Eligibility Criteria

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

You may qualify if:

• Patient must have signed a written informed consent prior to any trial specific procedures. (Note : When the patient is physically unable to give his/her written consent, a impartial witness of their choice, independent from the investigator or the sponsor, can confirm in signing the patient's consent)
• Men or women ≥ 18 years of age
• Histologically confirmed metastatic or locally advanced and unresectable triple-negative breast cancer, meeting both of the following criteria by local testing:
• HER2-low breast cancer, defined as either immunohistochemistry (IHC) 2+ / in situ hybridization (ISH)-negative or IHC 1+ (ISH-negative or untested), on either the primary or any metastatic site
• Estrogen receptor (ER) expression \<10% and progesterone receptor (PR) expression \<10% (Note: In case of bilateral breast cancer, participation in the study is permitted as long as both tumours correspond to a triple-negative breast cancer meeting the above criteria)
• Patient eligible to receive sacituzumab-govitecan and T-Dxd according to their indication
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Women of childbearing potential and male patients must agree to use adequate contraception for the duration of trial participation and up to 7 months after completing treatment for women and up to 4 months for men.
• A woman is considered to be of childbearing potential if she is not postmenopausal or has not undergone hysterectomy. Postmenopausal is defined as any of the following:
• Age ≥ 60 years Age \< 60 years and ≥ 12 continuous months of amenorrhea with no identified cause other than menopause Surgical sterilization (bilateral oophorectomy)
• \- Adequate organ and bone marrow function within 28 days before enrollment. The most recent results available must be used for all parameters below:
• Hemoglobin ≥ 9 g/dL. Red blood cell transfusion is not allowed within 1 week prior to screening assessment
• Absolute neutrophil count (ANC) ≥ 1,500/mm³. Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment
• Platelet count ≥ 100,000/mm³. Platelet transfusion is not allowed within 1 week prior to registration
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN) if no liver metastases, or \< 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastasis at baseline

You may not qualify if:

• Patient previously treated with any ADC targeting HER2 or TROP2
• Patient with uncontrolled or significant cardiovascular disease
• Patients with brain metastases (BM) except for asymptomatic treated BM not requiring ongoing corticosteroid treatment with stable lesions on baseline/screening brain MRI. Patients who require treatment of brain metastases are eligible after 14 days post surgery or radiation, if felt to be clinically stable and not requiring ongoing corticosteroid treatment
• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
• Any medical history or condition that per protocol or in the opinion of the investigator is incompatible with the study
• Patients with known allergy or severe hypersensitivity to any of the trial drugs or their excipients
• Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may cause misleading study interpretation or prevent completion of study procedures and followup examinations
• Patients with any other disease or illness that requires hospitalisation or is incompatible with the trial treatment are not eligible
• Pregnant or breast-feeding women at the time of randomization or intention to become pregnant during the study and up to 7 months after treatment
• Person deprived of their liberty or under protective custody or guardianship
• Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (2)

institut Paoli calmette

Marseille, 13009, France

Location

Gustave Roussy

Villejuif, 94800, France

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Neoplasm Metastasis; Breast Neoplasms

Interventions

sacituzumab govitecan; trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alexandre TASSIN DE NONNEVILLE

  Institut Paoli-Calmettes

  STUDY CHAIR

• François BERTUCCI

  Institut Paoli-Calmettes

  STUDY CHAIR

Central Study Contacts

GERALD BAGOE

CONTACT

+337714415 82; g-bagoe@unicancer.fr

Alexandre TASSIN DE NONNEVILLE

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: September 3, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)