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

NCT06680596 | Enrolling By Invitation Phase 2

• 2 other identifiers: UC-GMP-24022024-515349-41-00
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 34

Brief Summary

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).

Conditions

Breast Cancer Metastatic; Breast Cancer Stage IV

Keywords

HR+; HER2 low; HER2 ultralow; molecular screening; ctDNA; T-DXd; Antibody-drug conjugate; trastuzumab deruxtecan; Breast cancer metastatic

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  The progression-free survival is the length of time during and after treatment of the disease with T-DXd that a patient lives with the disease but it does not get worse.

  From first treatment administration to disease progression or death, up to 5 years

Secondary Outcomes (6)

• Overall survival (OS)

  From the first T-DXd administration to death due to any cause, up to 5 years

• Objective response Rate (ORR)

  From first T-DXd Administration to 6 months after the first administration of treatment, up to 5 years

• Duration of response (DoR)

  From the date of first documentation to disease progression or death, up to 5 years

• Clinical benefit rate (CBR)

  From first T-DXd Administration to 6 months after the first administration of treatment, up to 5 years

• Time to response (TTR)

  From the first T-DXd administration to objective response, up to 5 years

Study Arms (1)

T-DXd

EXPERIMENTAL

T-DXd will be administrated as an intra-venous injection of 5.4 mg/kg every three weeks (1 cycle = 21-day treatment).

Drug: trastuzumab derxutecan

Interventions

trastuzumab derxutecan DRUG

T-DXd will be administrated as an intra-venous injection of 5.4 mg/kg every three weeks (1 cycle = 21-day treatment).

T-DXd

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 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).

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• UNICANCER: lead
• AstraZeneca: collaborator
• Breast Cancer Research Foundation: collaborator

Study Sites (34)

Chu Amiens Picardie

Amiens, 80054, France

Location

Clinique de L'Europe Amiens - Cthe

Amiens, 80090, France

Location

Centre Hospitalier D'Auxerre

Auxerre, 89000, France

Location

Sainte Catherine Institut Du Cancer Avignon Provence

Avignon, 84918, France

Location

Centre Hospitalier de la Côte Basque

Bayonne, 64100, France

Location

Centre Hospitalier de Beauvais

Beauvais, 60021, France

Location

Hôpital Simone Veil de Blois

Blois, 41000, France

Location

Chu de Brest - Hôpital Cavale Blanche

Brest, 29200, France

Location

Clinique Pasteur Lanroze - Cfro - Groupe Vivalto Sante

Brest, 29200, France

Location

Centre Hospitalier William Morey

Chalon-sur-Saône, 71100, France

Location

Centre Hospitalier de Cholet

Cholet, 49300, France

Location

Pôle Santé République (Elsan)

Clermont-Ferrand, 63000, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Hospitalier Alpes Léman

Contamine-sur-Arve, 74130, France

Location

Chi Fréjus-Saint-Raphaël

Fréjus, 83608, France

Location

Chd Vendée

La Roche-sur-Yon, 85925, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hopital Prive Jean Mermoz

Lyon, 69008, France

Location

Clinique de La Sauvegarde

Lyon, 69009, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Icm Val D'Aurelle

Montpellier, 34298, France

Location

Medipôle de Nancy - Cog-Ilc (Polyclinique de Gentilly)

Nancy, 54100, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

Groupe Hospitalier Diaconesses Croix Saint-Simon

Paris, 75020, France

Location

Centre Hospitalier de Pau

Pau, 64046, France

Location

Hopital Privé Des Côtes D'Armor (Hpca) - Cario

Plérin, 22190, France

Location

Institut Godinot

Reims, 51100, France

Location

Centre Eugene Marquis

Rennes, France

Location

Chp Saint-Grégoire - Groupe Vivalto Sante

Saint-Grégoire, 35760, France

Location

Clinique Sainte-Anne - Gh Saint-Vincent

Strasbourg, 67000, France

Location

Hôpitaux Du Léman

Thonon-les-Bains, 74200, France

Location

Institut de Cancerologie de Lorraine

Vandœuvre-lès-Nancy, 054519, France

Location

Gustave Roussy

Villejuif, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Fabrice ANDRE, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: After an initial screening phase to identify patients with blood circulating tumours persistent, 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).

Study Record Dates

• First Submitted: November 7, 2024
• First Posted: November 8, 2024
• Study Start: July 30, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (34)