NeoAdjuvant Therapy With Trastuzumab-deruxtecan Versus Chemotherapy+Trastuzumab+Pertuzumab in HER2+ Early Breast Cancer

NCT05704829 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: WSG-AM12 (ADAPT-HER2-IV)
• Study Type: interventional
• Target: 402
• Locations: 1 country
• Sites: 43

Brief Summary

ADAPT-HER2-IV will address question of optimal neoadjuvant therapy in patients with less advanced -HER2+ EBC. ADAPT-HER2-IV is planned as a superiority trial to demonstrate higher pCR rates in both clinically relevant subgroups of low-intermediate risk HER2+ EBC. Moreover, it aims to demonstrate excellent survival in patients treated by T-DXd (with the use of standard chemotherapy at investigator´s decision restricted only to patients with substantial residual tumour burden after T-DXd-treatment).

Conditions

HER2-positive Early Breast Cancer

Keywords

HER2+; T-DXd; Trastuzumab-deruxtecan; pCR; intermediate risk; high risk; low risk; recurrence; neoadjuvant

Outcome Measures

Primary Outcomes (3)

• 1. pCR rate after neoadjuvant treatment

  defined as ypT0is/ypN0, to be compared between all T-DXd treated patients versus standard-of-care (PAC+T+P or PAC/DOC+Carbo+T+P) (pooled across cohorts)

  after 12 weeks of neoadjuvant treatment

• 1. pCR rate after neoadjuvant treatment

  defined as ypT0is/ypN0, to be compared between all T-DXd treated patients versus standard-of-care (PAC+T+P or PAC/DOC+Carbo+T+P) (pooled across cohorts)

  after 18 weeks of neoadjuvant treatment

• 2. distant disease-free survival (dDFS, according to STEEP 2.0 criteria)

  distant disease-free survival (dDFS, according to STEEP 2.0 criteria) in T-DXd treated patients (pooled across cohorts)

  after 3 years

Secondary Outcomes (13)

• clinical response

  after 6 weeks of treatment

• clinical response

  after 12 weeks of treatment

• clinical response

  after 18 (cohort 2) weeks of treatment

• dDFS in patients with pCR

  after 3 years

• pCR rates after different treatment durations

  12 versus 18 weeks

Study Arms (4)

T-DXd: HER2+ and low-intermediate risk for recurrence

EXPERIMENTAL

12 weeks T-DXd i.v. in neoadjuvant treatment; pCR dependent T-DXd for 1 year in total in postneoadjuvant treatment

Drug: Trastuzumab deruxtecan

T-DXd: HER2+ and intermediate-high risk for recurrence

EXPERIMENTAL

18 weeks T-DXd i.v. in neoadjuvant treatment; pCR dependent T-DXd for 1 year in total in postneoadjuvant treatment

Drug: Trastuzumab deruxtecan

Control: HER2+ and low-intermediate risk for recurrence

OTHER

Standard-of-Care-Treatment: 12 weeks PAC+T+P (standard-of-care) in neoadjuvant treatment; pCR dependent SOC chemotherapy +T+/-P or SOC T+/-P for 1 year in total in postneoadjuvant treatment

Drug: Standard-of-Care

Control: HER2+ and intermediate-high risk for recurrence

OTHER

Standard-of-Care-Treatment: 18 weeks PAC/DOC+Carbo+T+P (standard-of-care) in neoadjuvant treatment; pCR dependent SOC chemotherapy +T+/-P or SOC T+/-P for 1 year in total in postneoadjuvant treatment

Drug: Standard-of-Care

Interventions

Trastuzumab deruxtecan DRUG

T-DXd i.v.

Also known as: ENHERTU

T-DXd: HER2+ and intermediate-high risk for recurrence; T-DXd: HER2+ and low-intermediate risk for recurrence

Standard-of-Care DRUG

Chemotherapy+T+P

Also known as: Chemotherapy+T+P

Control: HER2+ and intermediate-high risk for recurrence; Control: HER2+ and low-intermediate risk for recurrence

Eligibility Criteria

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

You may qualify if:

• Female patients with invasive, untreated HER2+ breast cancer (as assessed by local pathology) maximum 6 weeks before registration (standard-of-care diagnostic biopsy according to current AGO guidelines)
• Age ≥18 years 3a. Cohort 1: low- to intermediate-risk for recurrence as per investigator´s decision (recommendation: cT1c - cT2 (1 - ≤3cm), cN0; cT1a/b excluded), OR 3b. Cohort 2: intermediate- to high-risk for recurrence as per investigator´s decision (recommendation: cT2 (\>3 - ≤5cm), cN0) 3c. Elderly patients (≥ 65 years) may be assigned to any cohort as per investigator's decision
• \. Written informed consent 5. LVEF ≥ 50% within 28 days before randomisation 6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 7. Adequate organ and bone marrow function within 14 days before randomisation 8. Adequate treatment washout period before randomisation (refer to protocol for detailed information) 9. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential (refer to protocol for detailed information) 10. Female subjects must not donate, or retrieve for their own use, ova from the time of randomisation and throughout the study treatment period, and for at least 7 months after the final study drug administration. (refer to protocol for detailed information)

You may not qualify if:

• Non-operable breast cancer including inflammatory breast cancer
• cT1a/b breast cancer
• Any previous history of invasive breast cancer
• Primary malignancies within 5 years, with the exception of adequately resected non-melanoma skin cancer, curatively treated in-situ disease
• Any evidence for existing metastatic disease (confirmed by CT Thorax/Abdomen, bone scan, or other methods according to clinical practice
• Previous or concurrent treatment with cytotoxic agents for any reason (except non-oncological reasons)
• Concurrent treatment with other experimental drugs and participation in another clinical trial with any investigational drug within 30 days prior to study entry
• Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study/inadequate organ function
• Reasons indicating risk of poor compliance
• Woman of child-bearing potential defined as a woman physiologically capable of becoming pregnant, and not using highly effective methods of contraception during the study treatment and for 3 months after stopping the treatment.
• Use of oral (oestrogen and progesterone), transdermal, injected, or implanted hormonal methods of contraception as well as hormonal replacement therapy.
• Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
• Patients with a medical history of myocardial infarction (MI) within 6 months before randomisation, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrolment to rule out MI.
• Corrected QT interval (QTcF) prolongation to \> 470 msec (females) based on average of the screening triplicate12-lead ECG.
• History of (non-infectious) ILD / pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.

Sponsors & Collaborators

• West German Study Group: lead
• AstraZeneca: collaborator

Study Sites (43)

Klinikum Mittelbaden, Brustzentrum

Baden-Baden, Baden-Wurttemberg, 76532, Germany

Location

Praxis für Interdisziplinäre Onkologie und Hämatologie (PIO)

Freiburg im Breisgau, Baden-Wurttemberg, 79110, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89075, Germany

Location

Hämotologisch onkologische Praxis Heinrich Bangerter Augsburg GbR

Augsburg, Bavaria, 86150, Germany

Location

Universitätsklinikum Augsburg / Klinik für Frauenheilkunde und Geburtshilfe

Augsburg, Bavaria, 86156, Germany

Location

Breast Center of the University of Munich (LMU) Universitätsfrauenklinik

Munich, Bavaria, 80336, Germany

Location

Rotkreuz Klinikum München

Munich, Bavaria, 80634, Germany

Location

Klinikum Bremerhaven Reinkenheide

Bremerhaven, City state Bremen, 27574, Germany

Location

Universittsklinikum am Klinikum Südstadt

Rostock, ecklenburg-Vorpommerns, 18059, Germany

Location

AGAPLESION Markus Krankenhaus Gynäkologie

Frankfurt am Main, Hesse, 60431, Germany

Location

Klinikum Frankfurt Höchst GmbH

Frankfurt am Main, Hesse, 65929, Germany

Location

Klinikum Kassel

Kassel, Hesse, 34125, Germany

Location

Studien GbR Braunschweig

Braunschweig, Lower Saxony, 38100, Germany

Location

Niels-Stensen-Kliniken Franziskus-Hospital

Georgsmarienhütte, Lower Saxony, 49124, Germany

Location

Ärztehaus am Bahnhofsplatz

Hildesheim, Lower Saxony, 31134, Germany

Location

MVZ Klinik Dr. Hancken GmbH

Stade, Lower Saxony, 21680, Germany

Location

Uniklinik RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, North Rhine-Westphalia, 33604, Germany

Location

St. Elisabeth Krankenhaus GmbH

Cologne, North Rhine-Westphalia, 50935, Germany

Location

Kliniken der Stadt Köln GmbH / Brustzentrum Holweide

Cologne, North Rhine-Westphalia, 51067, Germany

Location

Kliniken für Frauenheilkunde / Universitätsklinikum Düsseldorf

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Luisenkrankenhaus GmbH

Düsseldorf, North Rhine-Westphalia, 40235, Germany

Location

Sankt-Antonius-Hospital

Eschweiler, North Rhine-Westphalia, 52249, Germany

Location

Kliniken Essen-Mitte, Klinik für Senologie/Interdisziplinäres Brustzentrum

Essen, North Rhine-Westphalia, 45136, Germany

Location

Universitätsklinikum Essen, Brustzentrum

Essen, North Rhine-Westphalia, 45147, Germany

Location

Onkodok Gütersloh

Gütersloh, North Rhine-Westphalia, 33332, Germany

Location

St. Barbara Klinik

Hamm, North Rhine-Westphalia, 59073, Germany

Location

Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus

Mönchengladbach, North Rhine-Westphalia, 41061, Germany

Location

MVZ Media Vita am St. Franziskus Hospital

Münster, North Rhine-Westphalia, 48145, Germany

Location

Frauenklinik St. Louise-St. Vincenz-KH GmbH

Paderborn, North Rhine-Westphalia, 33098, Germany

Location

MKS St. Paulus GmbH

Schwerte, North Rhine-Westphalia, 58239, Germany

Location

Praxisnetzwerk Hämatologie und intern. Onkologie

Troisdorf, North Rhine-Westphalia, 53840, Germany

Location

Helios-Klinik Wuppertal

Wuppertal, North Rhine-Westphalia, 42283, Germany

Location

Klinikum Mutterhaus

Trier, Rhineland-Palatinate, 54290, Germany

Location

CaritasKlinikum Saarbrücken St. Theresia

Saarbrücken, Saarland, 66113, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

Location

Frauenklinik / Brustzentrum am Klinikum Obergölzsch Rodewisch

Rodewisch, Saxony, 08228, Germany

Location

UK Schleswig Holstein

Lübeck, Schleswig-Holsteins, 23538, Germany

Location

Charite Campus Mitte

Berlin, 10117, Germany

Location

Ev. Waldkrankenhaus Spandau

Berlin, 14589, Germany

Location

Universitätsklinikum Hamburg-Eppendorf / Klinik und Poliklinik für Gynäkologie

Hamburg, 20246, Germany

Location

Brustzentrum am Krankenhaus Jerusalem

Hamburg, 20357, Germany

Location

MeSH Terms

Conditions

Recurrence

Interventions

trastuzumab deruxtecan; Standard of Care

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Nadia Harbeck, Prof. Dr.

  Breast Centre, Dept. Obstetrics & Gynaecology and CCC Munich LMU University Hospital

  PRINCIPAL INVESTIGATOR

• Sherko Kuemmel, PRof. Dr.

  Breast Centre, Kliniken Essen Mitte Essen

  PRINCIPAL INVESTIGATOR

• Oleg Gluz, PD Dr.

  Breast Centre, Evang. Bethesda-Hospital Moenchengladbach

  PRINCIPAL INVESTIGATOR

• Michael Braun, Prof. Dr.

  Breast Centre Rotkreuzklinikum Munich

  PRINCIPAL INVESTIGATOR

• Monika Graeser, PD Dr.

  Breast Centre, Evang. Bethesda-Hospital Moenchengladbach

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: This is a multicentre, interventional, prospective, two-arm, randomised, open-label, controlled (neo-)adjuvant, phase-II trial evaluating the efficacy and safety of trastuzumab-deruxtecan (T-DXd) vs. standard-of-care paclitaxel + trastuzumab + pertuzumab (PAC+T+P) in low- to intermediate-risk or docetaxel/paclitaxel + carboplatin + trastuzumab + pertuzumab in intermediate- to high-risk HER2+ early breast cancer in pre- and postmenopausal women.

Study Record Dates

• First Submitted: December 28, 2022
• First Posted: January 30, 2023
• Study Start: February 5, 2024
• Primary Completion: June 18, 2025
• Study Completion (Estimated): June 1, 2029
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (43)