Detecting Tumor DNA in the Blood of HR+/HER2-low Metastatic Breast Cancer Patients to Find Candidates for T-DXd Therapy

Enrolling by invitation · Phase 2

Conditions studied: Breast Cancer Metastatic, Breast Cancer Stage IV

In brief

After an initial screening phase to identify patients with persistent blood circulating DNA tumors, patients will be enrolled in the treatment phase that was designed as an open-label, multicentre, phase II study, to test the efficacy of trastuzumab deruxtecan in terms of progression-free survival (PFS).

Key facts

Study ID

NCT06680596

Run by

UNICANCER

People needed

80

Starts

2025-07-30

Expected to finish

2029-08-01

Last updated by the study team

2026-08-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patient must have signed the written informed consent for screening phase prior to any trial specific procedures.
• Note: When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
• Patient is ≥18 years of age.
• Documented breast cancer that:
• Is metastatic and eligible to biopsy for subsequent histological or cytological confirmation,
• Is HER2 low (HER2 1+, or 2+ and in situ hybridization (ISH) negative) or HER2 ultra low (IHC 0 with incomplete and faint membrane staining in >0 and ≤10% of tumor cells) on the most recent tumor material available, as defined by the local pathologist under ASCO/CAP guidelines,
• Is HR-positive (positive for estrogen receptor or progesterone receptor ≥10% of tumor cell nuclei are immunoreactive) in the metastatic setting.
• Patient has either:
• a metastatic relapse during or within 1 year after termination of the adjuvant endocrine therapy (AI resistant), or
• a metastatic relapse more than one year of completing adjuvant AI or a de-novo metastatic breast cancer (AI sensitive/naive).
• For AI resistant population: patient has previously gone through the ctDNA screening part of the SAFIR 03 - SCREENING/ARRIBA study and fulfilled all the inclusion criteria and none of the exclusion criteria.
• Patient did not receive any therapy in the metastatic setting.
• Patient is eligible for a first-line treatment with a marketed CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) in combination with either AI or fulvestrant, according to its marketing authorisation.
• Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
• Patient has an adequate bone marrow and organ function.
• Patient has a measurable or an evaluable disease according to Response Evaluation Criteria In Solid Tumours version 1.1 (RECIST v1.1).
• Availability of an archived metastatic tumor sample (FFPE) for exploratory research. Bone metastasis are accepted if tissue is representative of tumor tissue (at least 10% tumor cellularity).
• Patient must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.
• Registration in a National Health Care System (or equivalent).

You may not qualify if…

• Patient is eligible to chemotherapy because of visceral crisis.
• Patient has a breast cancer amenable for resection or radiation therapy with curative intent.
• Prior exposure to antibody-drug conjugate or CDK4/6 inhibitors (in metastatic setting). CDK4/6 inhibitors given in adjuvant setting must be stopped for at least 12 months prior screening
• Patient who has initiated the CDK4/6 inhibitor treatment.
• Patient is unable to swallow tablets.
• Patient has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis requiring steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at baseline
• Patient has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
• Patient has a history of severe hypersensitivity reactions to other monoclonal antibodies.
• Person deprived of their liberty or under protective custody or guardianship.
• Social, familial, or geographic factors that would interfere with study participation or follow-up.
• TREATMENT PHASE_________________________________________________________
• Inclusion criteria
• Patient must have signed the written informed consent for the treatment phase prior to any trial specific procedures.
• Note: When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
• Patient must have discontinued CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) at least 7 days before enrolment, but no longer than 14 days
• Patients must present a no drop of ctDNA determined by a ctDNA assay after 4 weeks of standard of care treatment with a CDK4/6 inhibitor
• Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
• Left ventricular ejection fraction (LVEF) ≥50% within 28 days prior to enrolment.
• Participant has adequate bone marrow and organ function within 14 days before enrolment, defined as the following laboratory values:
• Absolute neutrophil count (ANC) ≥1500/mm³,
• platelet count ≥100,000/mm³,
• haemoglobin ≥9.0 g/dl,
• Serum creatinine ≤1.5 × upper limit of normal (ULN) or creatinine clearance ≥30 mL/min,
• Serum albumin ≥2.5 g/dL,
• Total bilirubin ≤1.5 × ULN (<3 ULN if Gilbert's disease),

Where it is running

• Chu Amiens Picardie — Amiens, France
• Clinique de L'Europe Amiens - Cthe — Amiens, France
• Centre Hospitalier D'Auxerre — Auxerre, France
• Sainte Catherine Institut Du Cancer Avignon Provence — Avignon, France
• Centre Hospitalier de la Côte Basque — Bayonne, France
• Centre Hospitalier de Beauvais — Beauvais, France
• Hôpital Simone Veil de Blois — Blois, France
• Centre Hospitalier de Boulogne-Sur-Mer — Boulogne-sur-Mer, France
• Chu de Brest - Hôpital Cavale Blanche — Brest, France
• Clinique Pasteur Lanroze - Cfro - Groupe Vivalto Sante — Brest, France
• Centre Hospitalier William Morey — Chalon-sur-Saône, France
• Centre Hospitalier de Cholet — Cholet, France
• Pôle Santé République (Elsan) — Clermont-Ferrand, France
• Centre Jean Perrin — Clermont-Ferrand, France
• Centre Hospitalier Alpes Léman — Contamine-sur-Arve, France
• Clinique de Flandre — Coudekerque-Branche, France
• Chi Fréjus-Saint-Raphaël — Fréjus, France
• Chd Vendée — La Roche-sur-Yon, France
• Centre Léon Bérard — Lyon, France
• Hopital Prive Jean Mermoz — Lyon, France
• Clinique de La Sauvegarde — Lyon, France
• Institut Paoli Calmettes — Marseille, France
• Icm Val D'Aurelle — Montpellier, France
• Medipôle de Nancy - Cog-Ilc (Polyclinique de Gentilly) — Nancy, France
• Centre Médico-Chirurgical (Cmc) Ambroise Paré-Hartmann — Neuilly-sur-Seine, France

Full record on ClinicalTrials.gov

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