NeoAdjuvant Therapy With Trastuzumab-deruxtecan Versus Chemotherapy+Trastuzumab+Pertuzumab in HER2+ Early Breast Cancer (ADAPTHER2-IV)

June 5, 2026 updated by: West German Study Group

NeoAdjuvant Dynamic Marker - Adjusted Personalized Therapy Comparing Trastuzumab-deruxtecan Versus Pacli-/Docetaxel+Carboplatin+Trastuzumab+Pertuzumab in HER2+ Early Breast Cancer

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

As the ADAPT-trials have clearly shown, pCR after 12 weeks of therapy, independent of the specific de-escalated neoadjuvant regimen and independent of further use of systemic chemotherapy, is an independent predictor of excellent prognosis4,19, also in patients treated by an antibody-drug conjugate alone (T-DM1), or in those receiving pertuzumab+trastuzumab+/-weekly paclitaxel.

In contrast to the adjuvant setting, none of the neoadjuvant trials so far has focused on HER2+ patients with a low-intermediate risk profile (e.g., node-negative patients with cT1-2 tumours). The ADAPT-HER2-IV trial aims to close this evidence gap.

Since there is some uncertainty about the optimal treatment duration in intermediate- to high-risk HER2+ EBC (e.g., tumour size >3 cm), we recommend using a longer 18-week taxane-based treatment (+/- carboplatin, at investigator´s decision) due to a large body of evidence for taxane + carboplatin combinations in patients in locally advanced stages.

Antibody-drug conjugates appear to be ideal candidate drugs for a "de-escalated" treatment due to their favourable safety (reduced alopecia, polyneuropathy rates, etc.) and a high efficacy profile (e.g., comparable pCR rates after 18 weeks of T-DM1 and taxane+pertuzumab+trastuzumab in the PREDIX HER2 trial20). Similarly to the classical chemotherapy landscape, optimal duration of antibody-drug conjugate-based neoadjuvant therapy remains unclear. pCR rates of around 40% to 60% were observed after 12 and 18 weeks of T-DM1 treatment (+/-pertuzumab) in the ADAPT TP, KRISTINE and PREDIX HER2 trials in HR+/HER2+ disease21,22. Moreover, long-term survival seem to be comparable between T-DM1+pertuzumab and older chemotherapy-containing regimens (docetaxel+carboplatin+trastuzumab+pertuzumab) despite of higher local progression rates and lower pCR in one study22.

Trastuzumab-deruxtecan (T-DXd) has shown promising activity in a small cohort of metastatic patients, including both HER2+ and HER2-low BC, pre-treated with several lines of therapy. Doi et al. reported overall response rates (ORR) of 58% and a disease control rate of 100% with overall survival at 12 months at in HER2+ disease pre-treated by T-DM1+/-pertuzumab in a late line setting23. T-DXd-therapy was associated with a manageable safety profile. Recently, clearly higher efficacy of T-DXd vs. T-DM1 was shown in second line metastatic breast cancer (MBC) in the DESTINY-03 trial24. Median progression free survival was not reached in T-DM1-arm vs. 6.8 months in the T-DXd-arm. This effect was independent of hormone receptor status, prior pertuzumab treatment, visceral metastases, number of prior therapy lines and presence of brain metastases. ORR was doubled (34.2 vs. 79.7%), favouring the T-DXd arm.

Study Type

Interventional

Enrollment (Estimated)

702

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Germany
      • Berlin, Germany, 10117
        • Active, not recruiting
        • Charite Campus Mitte
      • Berlin, Germany, 14589
        • Recruiting
        • Ev. Waldkrankenhaus Spandau
        • Contact:
          • Silke Polata, Dr.
        • Principal Investigator:
          • Silke Polata, Dr.
        • Sub-Investigator:
          • Sonja Cárdenas-Ovalle, Dr.
      • Hamburg, Germany, 20357
        • Recruiting
        • Brustzentrum am Krankenhaus Jerusalem
        • Principal Investigator:
          • Christian Schem, Prof. Dr.
        • Contact:
          • Christian Schem, Prof. Dr.
        • Contact:
          • Anne-Sophie Adam, Dr.
        • Sub-Investigator:
          • Anne-Sophie Adam, Dr.
      • Hamburg, Germany, 20246
        • Recruiting
        • Universitätsklinikum Hamburg-Eppendorf / Klinik und Poliklinik für Gynäkologie
        • Principal Investigator:
          • Lisa Steinhilper, Dr.
        • Contact:
          • Lisa Steinhilper, Dr.
        • Sub-Investigator:
          • Kerstin Riecken, Dr.
    • Baden-Wurttemberg
      • Baden-Baden, Baden-Wurttemberg, Germany, 76532
        • Recruiting
        • Klinikum Mittelbaden, Brustzentrum
        • Sub-Investigator:
          • Uwe Cramer, Dr.
        • Contact:
          • Antje Hahn, Dr.
        • Principal Investigator:
          • Anje Hahn, Dr.
      • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79110
        • Recruiting
        • Praxis für Interdisziplinäre Onkologie und Hämatologie (PIO)
        • Principal Investigator:
          • Matthias Zaiss, Dr.
        • Contact:
          • Matthias Zaiss, Dr.
        • Sub-Investigator:
          • Alexander Völkel, Dr.
      • Tübingen, Baden-Wurttemberg, Germany, 72076
        • Recruiting
        • Universitätsklinikum Tübingen
        • Contact:
          • Andreas Hartkopf, Prof. Dr.
        • Sub-Investigator:
          • Tobias Engler, Dr.
        • Principal Investigator:
          • Andreas Hartkopf, Prof. Dr.
      • Ulm, Baden-Wurttemberg, Germany, 89075
        • Recruiting
        • Universitatsklinikum Ulm
        • Contact:
          • Brigitte Rack, Prof. Dr.
        • Principal Investigator:
          • Brigitte Rack, Prof. Dr.
        • Sub-Investigator:
          • Angelina Fink, Dr.
    • Bavaria
      • Augsburg, Bavaria, Germany, 86150
        • Recruiting
        • Hämotologisch onkologische Praxis Heinrich Bangerter Augsburg GbR
        • Contact:
          • Bernhard Heinrich, Dr.
        • Sub-Investigator:
          • Markus Bangerter, Prof. Dr.
        • Principal Investigator:
          • Bernhard Heinrich, Dr.
      • Augsburg, Bavaria, Germany, 86156
        • Recruiting
        • Universitätsklinikum Augsburg / Klinik für Frauenheilkunde und Geburtshilfe
        • Contact:
          • Nina Ditsch, Prof. Dr.
        • Principal Investigator:
          • Nina Ditsch, Prof. Dr.
        • Sub-Investigator:
          • Melitta Köpke, Dr.
        • Sub-Investigator:
          • Jaqueline Sagasser, Dr.
      • Munich, Bavaria, Germany, 80336
        • Recruiting
        • Breast Center of the University of Munich (LMU) Universitätsfrauenklinik
        • Principal Investigator:
          • Nadia Harbeck, Prof. Dr.
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Rachel Würstlein, PD Dr.
      • Munich, Bavaria, Germany, 80634
        • Recruiting
        • Rotkreuz Klinikum München
        • Contact:
        • Sub-Investigator:
          • Claus Hanusch, Dr. med.
        • Principal Investigator:
          • Michael Braun, Prof. Dr.
        • Contact:
    • Free Hanseatic City of Bremen
      • Bremerhaven, Free Hanseatic City of Bremen, Germany, 27574
        • Active, not recruiting
        • Klinikum Bremerhaven Reinkenheide
    • Hesse
      • Frankfurt am Main, Hesse, Germany, 65929
        • Recruiting
        • Klinikum Frankfurt Höchst GmbH
        • Principal Investigator:
          • Joachim Rom, Prof. Dr.
        • Contact:
          • Joachim Rom, Prof. Dr.
        • Sub-Investigator:
          • Annette Junker-Stein, Dr.
      • Frankfurt am Main, Hesse, Germany, 60431
        • Recruiting
        • AGAPLESION Markus Krankenhaus Gynäkologie
        • Principal Investigator:
          • Marc Thill, Prof. Dr.
        • Sub-Investigator:
          • Christiane Brandi, Dr.
        • Contact:
          • Madeleine Modrow
      • Kassel, Hesse, Germany, 34125
        • Recruiting
        • Klinikum Kassel
        • Sub-Investigator:
          • Lydia Dautzenberg
        • Principal Investigator:
          • Yasmin Baila
        • Contact:
          • Yasmin Baila
    • Lower Saxony
      • Braunschweig, Lower Saxony, Germany, 38100
        • Recruiting
        • Studien GbR Braunschweig
        • Contact:
          • Janine Kreiss-Sender, Dr.
        • Principal Investigator:
          • Janine Kreiss-Sender, Dr.
        • Sub-Investigator:
          • Ralf Lorenz, Dr.
      • Georgsmarienhütte, Lower Saxony, Germany, 49124
        • Recruiting
        • Niels-Stensen-Kliniken Franziskus-Hospital
        • Principal Investigator:
          • Kerstin Lüdtke-Heckenkamp, Dr. med.
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Jost Wamhoff, Dr. med.
      • Hildesheim, Lower Saxony, Germany, 31134
        • Recruiting
        • Ärztehaus am Bahnhofsplatz
        • Principal Investigator:
          • Christoph Uleer, Dr.
        • Sub-Investigator:
          • Jasmin Pourfard, Dr.
        • Contact:
          • Christoph Uleer, Dr.
      • Stade, Lower Saxony, Germany, 21680
        • Recruiting
        • MVZ Klinik Dr. Hancken GmbH
        • Contact:
          • Birte Rahn
        • Principal Investigator:
          • Wiebke Timm, Dr.
        • Sub-Investigator:
          • Britta Heitmann, Dr.
        • Sub-Investigator:
          • Stefan Frühhauf, Prof. Dr.
    • Mecklenburg-Vorpommerns
      • Rostock, Mecklenburg-Vorpommerns, Germany, 18059
        • Recruiting
        • Universittsklinikum am Klinikum Südstadt
        • Contact:
          • Michaela Stecher
        • Principal Investigator:
          • Kristin Strauß, Dr.
        • Sub-Investigator:
          • Juliane Terpe-Weiland, Dr.
    • North Rhine-Westphalia
      • Aachen, North Rhine-Westphalia, Germany, 52074
        • Recruiting
        • Uniklinik RWTH Aachen
        • Contact:
          • Elmar Stickeler, Prof. Dr.
        • Principal Investigator:
          • Elmar Stickeler, Prof. Dr.
        • Sub-Investigator:
          • Brigitte Sophia Winkler, Dr.
      • Bielefeld, North Rhine-Westphalia, Germany, 33604
        • Recruiting
        • Onkologische Schwerpunktpraxis Bielefeld
        • Contact:
          • Siemke Steinke, Dr.
        • Contact:
          • Birgit Reunig-Bruns
        • Principal Investigator:
          • Siemke Steinke, Dr.
        • Sub-Investigator:
          • Hendrik Riesenberg, Dr. med.
      • Cologne, North Rhine-Westphalia, Germany, 50935
        • Recruiting
        • St. Elisabeth Krankenhaus GmbH
        • Contact:
          • Susanne Brandner, Dr.
        • Principal Investigator:
          • Susanne Brandner, Dr.
        • Sub-Investigator:
          • Claudia Schumacher, Dr.
      • Cologne, North Rhine-Westphalia, Germany, 51067
        • Recruiting
        • Kliniken der Stadt Köln GmbH / Brustzentrum Holweide
        • Principal Investigator:
          • Myriam Vincent
        • Contact:
          • Fatima Kourisna
        • Sub-Investigator:
          • Mathias Roland Warm, Prof. Dr.
      • Düsseldorf, North Rhine-Westphalia, Germany, 40225
        • Recruiting
        • Kliniken für Frauenheilkunde / Universitätsklinikum Düsseldorf
        • Contact:
          • Eugen Rückhaberle, Prof. Dr.
        • Principal Investigator:
          • Eugen Rückhaberle, Prof. Dr.
        • Sub-Investigator:
          • Tanja Fehm, Prof. Dr.
      • Düsseldorf, North Rhine-Westphalia, Germany, 40235
        • Active, not recruiting
        • Luisenkrankenhaus GmbH
      • Eschweiler, North Rhine-Westphalia, Germany, 52249
        • Recruiting
        • Sankt-Antonius-Hospital
        • Principal Investigator:
          • Peter Staib, Dr.
        • Contact:
          • Gabi Ziemons
        • Contact:
          • Franziska Wilhelm
        • Sub-Investigator:
          • Matthias Humberg, Dr. med
      • Essen, North Rhine-Westphalia, Germany, 45136
        • Recruiting
        • Kliniken Essen-Mitte, Klinik für Senologie/Interdisziplinäres Brustzentrum
        • Principal Investigator:
          • Sherko Kuemmel, Prof. Dr.
        • Contact:
          • Dorothea Schindowski
        • Sub-Investigator:
          • Jennifer Spönlein, Dr. med.
      • Essen, North Rhine-Westphalia, Germany, 45147
        • Recruiting
        • Universitätsklinikum Essen, Brustzentrum
        • Principal Investigator:
          • Oliver Hoffmann, Prof. Dr.
        • Sub-Investigator:
          • Ann-Kathrin Bittner, PD Dr.
        • Contact:
      • Gütersloh, North Rhine-Westphalia, Germany, 33332
        • Recruiting
        • Onkodok Gütersloh
        • Principal Investigator:
          • Reinhard Depenbusch, Dr.
        • Contact:
          • Reinhard Depenbusch, Dr.
        • Sub-Investigator:
          • Stefan Sonnenberg, Dr.
      • Hamm, North Rhine-Westphalia, Germany, 59073
        • Recruiting
        • St. Barbara Klinik
        • Principal Investigator:
          • Claudia Strunk, Dr.
        • Contact:
          • Claudia Strunk, Dr.
        • Sub-Investigator:
          • Wlodzimierz Badur, Dr.
      • Mönchengladbach, North Rhine-Westphalia, Germany, 41061
        • Recruiting
        • Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus
        • Contact:
          • Raquel von Schumann, Dr. med.
        • Principal Investigator:
          • Raquel von Schumann, Dr. med.
        • Sub-Investigator:
          • Oleg Gluz, PD Dr. med
      • Münster, North Rhine-Westphalia, Germany, 48145
        • Recruiting
        • MVZ Media Vita am St. Franziskus Hospital
        • Contact:
          • Stefanie Wiebe, Dr.
        • Principal Investigator:
          • Stefanie Wiebe, Dr.
        • Sub-Investigator:
          • Corina Neumann, Dr.
      • Paderborn, North Rhine-Westphalia, Germany, 33098
        • Recruiting
        • Frauenklinik St. Louise-St. Vincenz-KH GmbH
        • Contact:
          • Michael Patrick Lux, Prof. Dr.
        • Principal Investigator:
          • Michael Patrick Lux, Prof. Dr.
        • Sub-Investigator:
          • Michaela Wüllner, Dr.
      • Schwerte, North Rhine-Westphalia, Germany, 58239
        • Recruiting
        • MKS St. Paulus GmbH
        • Sub-Investigator:
          • Michael Hartmann, Dr.
        • Contact:
          • Johanna Westkämper
        • Principal Investigator:
          • Asja Sborowski, Dr.
      • Troisdorf, North Rhine-Westphalia, Germany, 53840
        • Recruiting
        • Praxisnetzwerk Hämatologie und intern. Onkologie
        • Contact:
          • Andreas Diel
        • Principal Investigator:
          • Andreas Diel
        • Sub-Investigator:
          • Ernst Rodermann, Dr.
      • Witten, North Rhine-Westphalia, Germany, 58452
        • Not yet recruiting
        • Marien-Hospital Witten
        • Contact:
          • Monika Graeser, Prof. Dr.
        • Principal Investigator:
          • Monika Graeser, Prof. Dr.
      • Wuppertal, North Rhine-Westphalia, Germany, 42283
        • Recruiting
        • Helios-Klinik Wuppertal
        • Sub-Investigator:
          • Oliver Schmalz, Dr.
        • Contact:
          • Vesna Bjelic-Radisic, Prof. Dr.
        • Principal Investigator:
          • Vesna Bjelic-Radisic, Prof. Dr.
        • Sub-Investigator:
          • Bianca Böning, Dr.
    • Rhineland-Palatinate
      • Trier, Rhineland-Palatinate, Germany, 54290
        • Recruiting
        • Klinikum Mutterhaus
        • Contact:
          • Sebastian Jud, Prof. Dr.
        • Principal Investigator:
          • Sebastian Jud, Prof. Dr.
        • Sub-Investigator:
          • Marion Klieden, Dr.
    • Saarland
      • Saarbrücken, Saarland, Germany, 66113
        • Recruiting
        • CaritasKlinikum Saarbrücken St. Theresia
        • Contact:
          • Mustafa Deryal, Dr.
        • Principal Investigator:
          • Mustafa Deryal, Dr.
        • Sub-Investigator:
          • Carolin Beckmann, Dr.
    • Saxony
      • Leipzig, Saxony, Germany, 04103
        • Recruiting
        • Universitätsklinikum Leipzig
        • Principal Investigator:
          • Bahriye Aktas, Prof. Dr.
        • Contact:
          • Bahriye Aktas, Prof. Dr.
        • Sub-Investigator:
          • Susanne Briest, Dr.
        • Sub-Investigator:
          • Dirk Forstmeyer, Dr.
      • Rodewisch, Saxony, Germany, 08228
        • Recruiting
        • Frauenklinik / Brustzentrum am Klinikum Obergölzsch Rodewisch
        • Contact:
          • Barbara Prediger, Dr.
        • Principal Investigator:
          • Barbara Prediger, Dr.
        • Sub-Investigator:
          • Stefanie Strobel, Dr.
        • Sub-Investigator:
          • Jiri Pomyje, MUDr.
    • Schleswig-Holsteins
      • Lübeck, Schleswig-Holsteins, Germany, 23538
        • Recruiting
        • UK Schleswig Holstein
        • Contact:
          • Maggie Banys-Paluchowski, Prof. Dr.
        • Principal Investigator:
          • Maggie Banys-Paluchowski, Prof. Dr.
        • Sub-Investigator:
          • Kaschner Katharina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Patients eligible for inclusion in this study must meet all the following criteria:

1. 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) 2. Age ≥18 years 3a. Cohort 1: low- to intermediate-risk for recurrence as per investigator´s decision (recommendation: cT1c - cT2 (1 - ≤3cm) AND cN0; cT1a/b, cN0 excluded), OR 3b. Cohort 2: intermediate- to high-risk for recurrence as per investigator´s decision (recommendation: cT2 (>3 - ≤5cm), cN0) 3c. Cohort 3: intermediate- to high-risk for recurrence as per investigator´s decision, (recommendation: clinical stage II (cT2, cN0); cT1c, cN0 only if neoadjuvant treatment intended) 4. Written informed consent 5. LVEF ≥ 50% within 28 days before randomisation 6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 7. Adequate bone marrow and organ function within 14 days before randomisation as defined by the following laboratory values:

  • absolute neutrophil count ≥ 1.5 × 109/L,
  • platelets ≥ 100 × 109/L,
  • haemoglobin ≥ 9.0 g/dL:
  • estimated glomerular filtration rate (eGFR) ≥ 30 mL/min by a Cockcroft-Gault formula,
  • INR ≤ 1.5,
  • serum creatinine < 1.5 mg/dL,
  • total bilirubin < ULN, except for patients with Gilbert's Syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN,
  • aspartate transaminase (AST) < 2.5 × ULN,
  • alanine transaminase (ALT) < 2.5 × ULN. 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) Post-menopausal status is accepted for women, who at the time of initiation of study medication, either
  • had underwent bilateral oophorectomy, or
  • are ≥ 60 years of age, or
  • are < 60 years of age and amenorrhoeic for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression)

  • and/or whose FSH- and oestradiol-blood values are within the postmenopausal range per local laboratory normal range.

    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.

Exclusion Criteria:

Patients eligible for inclusion in this study must not meet any of the following criteria:

  1. 1. Non-operable breast cancer including inflammatory breast cancer
  2. cT1a/b, cN0 breast cancer
  3. Any previous history of invasive breast cancer

  4. Primary malignancies within 5 years, with the exception of

    • adequately resected non-melanoma skin cancer
    • curatively treated in-situ disease
  5. Any evidence for existing metastatic disease (confirmed by CT Thorax/Abdomen, bone scan, or other methods according to clinical practice
  6. Previous or concurrent treatment with cytotoxic agents for any reason (except non-oncological reasons)
  7. Concurrent treatment with other experimental drugs and participation in another clinical trial with any investigational drug within 30 days prior to study entry
  8. Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study/inadequate organ function
  9. Reasons indicating risk of poor compliance
  10. 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 7 months after stopping the treatment.
  11. Use of oral (oestrogen and progesterone), transdermal, injected, or implanted hormonal methods of contraception as well as hormonal replacement therapy.
  12. 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.
  13. 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.
  14. Corrected QT interval (QTcF) prolongation to > 470 msec (females) based on average of the screening 12-lead ECG.
  15. 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.

  16. Lung criteria:

    • Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder
    • Any autoimmune, connective tissue or inflammatory disorders (e.g., Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of randomisation.
    • Prior pneumonectomy (complete)
    • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
  17. Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients should be tested for HIV prior to randomisation if required by local regulations or ethics committee (EC).

  18. Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of trastuzumab deruxtecan or carboplatin.

    Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IMP.

  19. Known allergy or hypersensitivity to study treatment (T-DXd), to comparator (SoC-) treatment, or any of the study drug / comparator (SoC-) excipients.
  20. History of severe hypersensitivity reactions to other monoclonal antibodies.
  21. Pregnant or breastfeeding female patients, or patients who are planning to become pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: T-DXd 12 weeks: HER2+ and low-intermediate risk for recurrence
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 i.v.
Other Names:
  • ENHERTU
Experimental: T-DXd 18 weeks: HER2+ and intermediate-high risk for recurrence
18 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 i.v.
Other Names:
  • ENHERTU
Other: Control SoC CTx 12 weeks: HER2+ and low-intermediate risk for recurrence
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
Chemotherapy+T+P
Other Names:
  • Chemotherapy+T+P
Other: Control SoC CTx 18 weeks: HER2+ and intermediate-high risk for recurrence
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
Chemotherapy+T+P
Other Names:
  • Chemotherapy+T+P
Experimental: T-DXd 12 weeks + SoC CTx 6 weeks

12 weeks T-DXd i.v. follwed by 6 weeks SoC chemotherapy in neoadjuvant treatment; pCR dependent postneoadjuvant treatment:

  • non-pCR: 14 cycles of T-DXd is strongly recommended or SoC treatment, i.e., chemotherapy and anti-HER2-treatment, including T-DM1 at investigator´s decision
  • pCR: SoC treatment, e.g., T +/- P or T-DM1 (at investigator´s decision)
Drug: Trastuzumab deruxtecan
T-DXd i.v.
Other Names:
  • ENHERTU
Drug: Standard-of-Care
Chemotherapy+T+P
Other Names:
  • Chemotherapy+T+P
Experimental: T-DXd 12 weeks + SoC CTx 12 weeks

12 weeks T-DXd i.v. follwed by 12 weeks SoC chemotherapy in neoadjuvant treatment; pCR dependent postneoadjuvant treatment:

  • non-pCR: 14 cycles of T-DXd is strongly recommended or SoC treatment, i.e., chemotherapy and anti-HER2-treatment, including T-DM1 at investigator´s decision
  • pCR: SoC treatment, e.g., T +/- P or T-DM1 (at investigator´s decision) Therapy for patients with non-pCR who received neoadjuvant T-DXd (12 weeks) + 12 weeks (4 cycles) of SoC chemotherapy will exceed total therapy over one year. Here, approximately 66 weeks are considered as maximum therapy (individual variations may apply)
Drug: Trastuzumab deruxtecan
T-DXd i.v.
Other Names:
  • ENHERTU
Drug: Standard-of-Care
Chemotherapy+T+P
Other Names:
  • Chemotherapy+T+P
Other: SoC CTx 18 weeks

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

  • non-pCR (in particular ypT >1b (5 mm) or ypN+: 14 cycles with T-DXd recommended
  • pCR: SoC treatment, e.g., T +/- P or T-DM1 (at investigator´s decision) Therapy for patients with non-pCR who received neoadjuvant SoC chemotherapy will exceed total therapy over one year. Here, approximately 60 weeks are considered as maximum therapy (individual variations may apply).
Drug: Standard-of-Care
Chemotherapy+T+P
Other Names:
  • Chemotherapy+T+P

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse drug reactions with CTCAE-grade 3 or higher, compared between patients treated with T-DXd neoadjuvant monotherapy for 18 weeks (part 1, cohort 2) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
Time Frame: after 18 weeks of neoadjuvant treatment
compared between patients treated with T-DXd neoadjuvant monotherapy for 18 weeks (part 1, cohort 2) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 18 weeks of neoadjuvant treatment
distant disease-free survival (dDFS, according to STEEP 2.0 criteria): T-DXd
Time Frame: after 3 years
dDFS in patients with T-DXd neoadjuvant monotherapy (pooled experimental treatment arms of part 1, pooled cohorts 1 and 2)
after 3 years
distant disease-free survival (dDFS, according to STEEP 2.0 criteria): CTx
Time Frame: after 3 years
in patients with T-DXd neoadjuvant therapy followed by CHT (pooled experimental treatment arms of part 2, cohort 3)
after 3 years
pCR rate after neoadjuvant treatment
Time Frame: after 18 weeks of neoadjuvant treatment
defined as ypT0is/ypN0, compared between patients treated with T-DXd neoadjuvant monotherapy (pooled experimental treatment arms of part 1, pooled cohorts 1 and 2) compared to patients of corresponding standard-of-care treatments (DOC/PAC+T+P or DOC/PAC+Carbo+T+P) (pooled standard-of-care treatment arms of part 1, pooled cohorts 1 and 2)
after 18 weeks of neoadjuvant treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
iDFS
Time Frame: at end of study
survival endpoint STEEP 2.0
at end of study
OS
Time Frame: at end of study
survival endpoint STEEP 2.0
at end of study
LRFS
Time Frame: at end of study
survival endpoint STEEP 2.0
at end of study
BCFS
Time Frame: at end of study
survival endpoint STEEP 2.0
at end of study
DRFI
Time Frame: at end of study
survival endpoint STEEP 2.0
at end of study
QOL
Time Frame: after 1 year
health-related quality of life
after 1 year
distant disease-free survival (dDFS, according to STEEP 2.0 criteria): 18 weeks
Time Frame: after 3 years
compared between patients treated with T-DXd neoadjuvant monotherapy for 18 weeks (part 1, cohort 2) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 3 years
distant disease-free survival (dDFS, according to STEEP 2.0 criteria): 12 weeks
Time Frame: after 3 years
compared between patients treated with T-DXd neoadjuvant monotherapy for 12 weeks (part 1, cohort 1) and patients treated with SoC for 12 weeks (part 1, cohort 1) 2 and 3 pooled)
after 3 years
distant disease-free survival (dDFS, according to STEEP 2.0 criteria): 12 plus 6 weeks
Time Frame: after 3 years
compared between patients treated with T-DXd neoadjuvant therapy for 12 weeks followed by 6 weeks CHT (part 2, cohort 3) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 3 years
distant disease-free survival (dDFS, according to STEEP 2.0 criteria): 12 plus 12 weeks
Time Frame: after 3 years
compared between patients treated with T-DXd neoadjuvant therapy for 12 weeks followed by 12 weeks CHT (part 2, cohort 3) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 3 years
distant disease-free survival (dDFS, according to STEEP 2.0 criteria)
Time Frame: after 3 years
in patients with pCR after neoadjuvant treatment without further chemotherapy: It should be tested whether 3-year dDFS of each arm exceeds 92% (literature data)
after 3 years
pCR rate: 18 weeks
Time Frame: after 18 weeks treatment
defined as ypTis/ypN0 in patients treated with T-DXd neoadjuvant monotherapy for 18 weeks (part 1, cohort 2) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 18 weeks treatment
pCR rate: 12 weeks
Time Frame: after 12 weeks treatment
defined as ypTis/ypN0 in patients treated with T-DXd neoadjuvant monotherapy for 12 weeks (part 1, cohort 1) and patients treated with SoC for 12 weeks (part 1, cohort 1)
after 12 weeks treatment
pCR rate: 12 plus 12 weeks
Time Frame: after 24 weeks treatment
defined as ypTis/ypN0 in patients treated with T-DXd neoadjuvant therapy for 12 weeks followed by 12 weeks CHT (part 2, cohort 3) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 24 weeks treatment
Clinical response after 6 weeks
Time Frame: after 6 weeks treatment
defined as either cCR, cPR, cSD, after 6 weeks of neoadjuvant treatment compared between T-DXd treated patients and SoC treated patients
after 6 weeks treatment
Clinical response after 12 weeks
Time Frame: after 12 weeks treatment
defined as either cCR, cPR, cSD, after 12 weeks of neoadjuvant treatment compared between T-DXd treated patients and SoC treated patients
after 12 weeks treatment
Clinical response after 24 weeks
Time Frame: after 24 weeks treatment
defined as either cCR, cPR, cSD, after 24 weeks of neoadjuvant treatment compared between T-DXd treated patients and SoC treated patients
after 24 weeks treatment
adverse drug reaction with CTCAE-grade 3 or higher: 12 weeks mono
Time Frame: after 12 weeks treatment
Number of ADR with CTCAE-grade 3 or higher in patients treated with T-DXd neoadjuvant monotherapy for 12 weeks (part 1, cohort 1) and patients treated with SoC for 12 weeks (part 1, cohort 1)
after 12 weeks treatment
adverse drug reaction with CTCAE-grade 3 or higher: 18 weeks combined
Time Frame: after 18 weeks treatment
Number of ADR with CTCAE-grade 3 or higher in patients treated with T-DXd neoadjuvant therapy for 12 weeks followed by 6 weeks CHT (part 2, cohort 3) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 18 weeks treatment
adverse drug reaction with CTCAE-grade 3 or higher: 24 weeks combined
Time Frame: after 24 weeks treatment
Number of ADR with CTCAE-grade 3 or higher in patients treated with T-DXd neoadjuvant therapy for 12 weeks followed by 12 weeks CHT (part 2, cohort 3) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 24 weeks treatment
Proportion of patients with any TEAE: 18 weeks mono
Time Frame: after 18 weeks treatment
compared between patients treated with T-DXd neoadjuvant monotherapy for 18 weeks (part 1, cohort 2) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 18 weeks treatment
Proportion of patients with any TEAE: 12 weeks mono
Time Frame: after 12 weeks treatment
compared between patients treated with T-DXd neoadjuvant monotherapy for 12 weeks (part 1, cohort 1 ) and patients treated with SoC for 12 weeks (part 1, cohort 1)
after 12 weeks treatment
Proportion of patients with any TEAE: 18 weeks combined
Time Frame: after 18 weeks treatment
compared between patients treated with T-DXd neoadjuvant therapy for 12 weeks followed by 6 weeks CHT (part 2, cohort 3) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 18 weeks treatment
Proportion of patients with any TEAE: 24 weeks combined
Time Frame: after 24 weeks treatment
compared between patients treated with T-DXd neoadjuvant therapy for 12 weeks followed by 12 weeks CHT (part 2, cohort 3) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 24 weeks treatment
Frequency of TEAE: 12 weeks
Time Frame: after 12 weeks treatment
in all T-DXd based neoadjuvant treatment regimens as well as in SoC for 12 weeks (part 1, cohort 1)
after 12 weeks treatment
Frequency of TEAE : 18 weeks
Time Frame: after 18 weeks treatment
in all T-DXd based neoadjuvant treatment regimens as well as in SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 18 weeks treatment
Proportion of patients with adverse event of special interest (AESI): 18 weeks mono
Time Frame: after 18 weeks treatment
AESI) (interstitial lung disease, QT time prolongation, LVEF decrease, infusion related reactions) compared between patients treated with T-DXd neoadjuvant monotherapy for 18 weeks (part 1, cohort 2) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 18 weeks treatment
Proportion of patients with adverse event of special interest (AESI): 12 weeks mono
Time Frame: after 12 weeks treatment
AESI) (interstitial lung disease, QT time prolongation, LVEF decrease, infusion related reactions) compared between patients treated with T-DXd neoadjuvant monotherapy for 12 weeks (part 1, cohort 1 ) and patients treated with SoC for 12 weeks (part 1, cohort1 )
after 12 weeks treatment
Proportion of patients with adverse event of special interest (AESI): 18 weeks combined
Time Frame: after 18 weeks treatment
AESI) (interstitial lung disease, QT time prolongation, LVEF decrease, infusion related reactions) compared between patients treated with T-DXd neoadjuvant therapy for 12 weeks followed by 6 weeks CHT (part 2, cohort 3) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 18 weeks treatment
Proportion of patients with adverse event of special interest (AESI): 24 weeks combined
Time Frame: after 24 weeks treatment
AESI) (interstitial lung disease, QT time prolongation, LVEF decrease, infusion related reactions) compared between patients treated with T-DXd neoadjuvant therapy for 12 weeks followed by 12 weeks CHT (part 2, cohort 3) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 24 weeks treatment
Frequency of AESI in T-DXd
Time Frame: after 12 weeks treatment
in all four T-DXd based neoadjuvant treatment regimens
after 12 weeks treatment
Frequency of AESI in SoC: 12 weeks
Time Frame: after 12 weeks treatment
in SoC for 12 weeks (part 1, cohort 1)
after 12 weeks treatment
Frequency of AESI in SoC: 18 weeks
Time Frame: after 18 weeks treatment
in SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
after 18 weeks treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West German Study Group

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: 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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 5, 2024

Primary Completion (Estimated)

June 1, 2030

Study Completion (Estimated)

September 1, 2030

Study Registration Dates

First Submitted

December 28, 2022

First Submitted That Met QC Criteria

January 19, 2023

First Posted (Actual)

January 30, 2023

Study Record Updates

Last Update Posted (Actual)

June 9, 2026

Last Update Submitted That Met QC Criteria

June 5, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WSG-AM12 (ADAPT-HER2-IV)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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