HER2-positive Early Breast CancerPhase 2ADAPTHER2-IVNCT05704829
NeoAdjuvant Therapy With Trastuzumab-deruxtecan Versus Chemotherapy+Trastuzumab+Pertuzumab in HER2+ Early Breast Cancer
A Phase 2 study testing Trastuzumab deruxtecan and Standard-of-Care in people with HER2-positive Early Breast Cancer, run by Women's Cancer Study Group GmbH at 44 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- HER2-positive Early Breast Cancer
- What is being tested?
- Trastuzumab deruxtecan and Standard-of-Care
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 702 participants
- Where
- 44 sitesGermany
- Study dates
- 5 Feb 2024to Sep 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
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- 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.
Who cannot join
- Patients eligible for inclusion in this study must not meet any of the following criteria:
- 1. Non-operable breast cancer including inflammatory breast cancer
- cT1a/b, cN0 breast cancer
- Any previous history of invasive breast cancer
- Primary malignancies within 5 years, with the exception of
- adequately resected non-melanoma skin cancer
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- 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 7 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 12-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.
- 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
- 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).
- 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.
- Known allergy or hypersensitivity to study treatment (T-DXd), to comparator (SoC-) treatment, or any of the study drug / comparator (SoC-) excipients.
- History of severe hypersensitivity reactions to other monoclonal antibodies.
- Pregnant or breastfeeding female patients, or patients who are planning to become pregnant
Trial locations and contacts
44 sites in 1 country. Contact the study team or a site near you to ask about taking part.
44 sites in 1 country
Germany44 sites, 41 recruiting
- Recruiting
Uniklinik RWTH Aachen
Aachen, North Rhine-Westphalia, 52074
Elmar Stickeler, Prof. Dr.
Elmar Stickeler, Prof. Dr.
- Recruiting
Hämotologisch onkologische Praxis Heinrich Bangerter Augsburg GbR
Augsburg, Bavaria, 86150
Bernhard Heinrich, Dr.
Bernhard Heinrich, Dr.
- Recruiting
Universitätsklinikum Augsburg / Klinik für Frauenheilkunde und Geburtshilfe
Augsburg, Bavaria, 86156
Nina Ditsch, Prof. Dr.
Nina Ditsch, Prof. Dr.
- Recruiting
Klinikum Mittelbaden, Brustzentrum
Baden-Baden, Baden-Wurttemberg, 76532
Antje Hahn, Dr.
Anje Hahn, Dr.
- Active, not recruiting
Charite Campus Mitte
Berlin, 10117
- Recruiting
Ev. Waldkrankenhaus Spandau
Berlin, 14589
Silke Polata, Dr.
Silke Polata, Dr.
- Recruiting
Onkologische Schwerpunktpraxis Bielefeld
Bielefeld, North Rhine-Westphalia, 33604
Siemke Steinke, Dr.
Birgit Reunig-Bruns
- Recruiting
Studien GbR Braunschweig
Braunschweig, Lower Saxony, 38100
Janine Kreiss-Sender, Dr.
Janine Kreiss-Sender, Dr.
- Active, not recruiting
Klinikum Bremerhaven Reinkenheide
Bremerhaven, Free Hanseatic City of Bremen, 27574
- Recruiting
St. Elisabeth Krankenhaus GmbH
Cologne, North Rhine-Westphalia, 50935
Susanne Brandner, Dr.
Susanne Brandner, Dr.
- Recruiting
Kliniken der Stadt Köln GmbH / Brustzentrum Holweide
Cologne, North Rhine-Westphalia, 51067
Fatima Kourisna
Myriam Vincent
- Recruiting
Kliniken für Frauenheilkunde / Universitätsklinikum Düsseldorf
Düsseldorf, North Rhine-Westphalia, 40225
Eugen Rückhaberle, Prof. Dr.
Eugen Rückhaberle, Prof. Dr.
- Active, not recruiting
Luisenkrankenhaus GmbH
Düsseldorf, North Rhine-Westphalia, 40235
- Recruiting
Sankt-Antonius-Hospital
Eschweiler, North Rhine-Westphalia, 52249
Gabi Ziemons
Franziska Wilhelm
- Recruiting
Kliniken Essen-Mitte, Klinik für Senologie/Interdisziplinäres Brustzentrum
Essen, North Rhine-Westphalia, 45136
Dorothea Schindowski
Sherko Kuemmel, Prof. Dr.
- Recruiting
Universitätsklinikum Essen, Brustzentrum
Essen, North Rhine-Westphalia, 45147
Oliver Hoffmann, Prof. Dr., oliver.hoffmann@uk-essen.de
Oliver Hoffmann, Prof. Dr.
- Recruiting
AGAPLESION Markus Krankenhaus Gynäkologie
Frankfurt am Main, Hesse, 60431
Madeleine Modrow
Marc Thill, Prof. Dr.
- Recruiting
Klinikum Frankfurt Höchst GmbH
Frankfurt am Main, Hesse, 65929
Joachim Rom, Prof. Dr.
Joachim Rom, Prof. Dr.
- Recruiting
Praxis für Interdisziplinäre Onkologie und Hämatologie (PIO)
Freiburg im Breisgau, Baden-Wurttemberg, 79110
Matthias Zaiss, Dr.
Matthias Zaiss, Dr.
- Recruiting
Niels-Stensen-Kliniken Franziskus-Hospital
Georgsmarienhütte, Lower Saxony, 49124
Kerstin Lüdtke-Heckenkamp, Dr. med., +49 541 5022466, jost.wamhoff@niels-stensen-kliniken.de
Jost Wamhoff, Dr. med., +49 541 5022466, jost.wamhoff@niels-stensen-kliniken.de
- Recruiting
Onkodok Gütersloh
Gütersloh, North Rhine-Westphalia, 33332
Reinhard Depenbusch, Dr.
Reinhard Depenbusch, Dr.
- Recruiting
Universitätsklinikum Hamburg-Eppendorf / Klinik und Poliklinik für Gynäkologie
Hamburg, 20246
Lisa Steinhilper, Dr.
Lisa Steinhilper, Dr.
- Recruiting
Brustzentrum am Krankenhaus Jerusalem
Hamburg, 20357
Christian Schem, Prof. Dr.
Anne-Sophie Adam, Dr.
- Recruiting
St. Barbara Klinik
Hamm, North Rhine-Westphalia, 59073
Claudia Strunk, Dr.
Claudia Strunk, Dr.
- Recruiting
Ärztehaus am Bahnhofsplatz
Hildesheim, Lower Saxony, 31134
Christoph Uleer, Dr.
Christoph Uleer, Dr.
- Recruiting
Klinikum Kassel
Kassel, Hesse, 34125
Yasmin Baila
Yasmin Baila
- Recruiting
Universitätsklinikum Leipzig
Leipzig, Saxony, 04103
Bahriye Aktas, Prof. Dr.
Bahriye Aktas, Prof. Dr.
- Recruiting
UK Schleswig Holstein
Lübeck, Schleswig-Holsteins, 23538
Maggie Banys-Paluchowski, Prof. Dr.
Maggie Banys-Paluchowski, Prof. Dr.
- Recruiting
Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus
Mönchengladbach, North Rhine-Westphalia, 41061
Raquel von Schumann, Dr. med.
Raquel von Schumann, Dr. med.
- Recruiting
Breast Center of the University of Munich (LMU) Universitätsfrauenklinik
Munich, Bavaria, 80336
Nadia Harbeck, Prof. Dr., +49897095 ext. 4531, nadia.harbeck@med.uni-muenchen.de
Farangis Stahl, farangis.stahl@med-uni-muenchen.de
- Recruiting
Rotkreuz Klinikum München
Munich, Bavaria, 80634
Michael Braun, Prof. Dr., +49 89 130330, michael.braun@swmbrk.de
Harry Reisch, +49 89 13033662, harry.reisch@swmbrk.de
- Recruiting
MVZ Media Vita am St. Franziskus Hospital
Münster, North Rhine-Westphalia, 48145
Stefanie Wiebe, Dr.
Stefanie Wiebe, Dr.
- Recruiting
Frauenklinik St. Louise-St. Vincenz-KH GmbH
Paderborn, North Rhine-Westphalia, 33098
Michael Patrick Lux, Prof. Dr.
Michael Patrick Lux, Prof. Dr.
- Recruiting
Frauenklinik / Brustzentrum am Klinikum Obergölzsch Rodewisch
Rodewisch, Saxony, 08228
Barbara Prediger, Dr.
Barbara Prediger, Dr.
- Recruiting
Universittsklinikum am Klinikum Südstadt
Rostock, Mecklenburg-Vorpommerns, 18059
Michaela Stecher
Kristin Strauß, Dr.
- Recruiting
CaritasKlinikum Saarbrücken St. Theresia
Saarbrücken, Saarland, 66113
Mustafa Deryal, Dr.
Mustafa Deryal, Dr.
- Recruiting
MKS St. Paulus GmbH
Schwerte, North Rhine-Westphalia, 58239
Johanna Westkämper
Asja Sborowski, Dr.
- Recruiting
MVZ Klinik Dr. Hancken GmbH
Stade, Lower Saxony, 21680
Birte Rahn
Wiebke Timm, Dr.
- Recruiting
Klinikum Mutterhaus
Trier, Rhineland-Palatinate, 54290
Sebastian Jud, Prof. Dr.
Sebastian Jud, Prof. Dr.
- Recruiting
Praxisnetzwerk Hämatologie und intern. Onkologie
Troisdorf, North Rhine-Westphalia, 53840
Andreas Diel
Andreas Diel
- Recruiting
Universitätsklinikum Tübingen
Tübingen, Baden-Wurttemberg, 72076
Andreas Hartkopf, Prof. Dr.
Andreas Hartkopf, Prof. Dr.
- Recruiting
Universitätsklinikum Ulm
Ulm, Baden-Wurttemberg, 89075
Brigitte Rack, Prof. Dr.
Brigitte Rack, Prof. Dr.
- Not yet recruiting
Marien-Hospital Witten
Witten, North Rhine-Westphalia, 58452
Monika Graeser, Prof. Dr.
Monika Graeser, Prof. Dr.
- Recruiting
Helios-Klinik Wuppertal
Wuppertal, North Rhine-Westphalia, 42283
Vesna Bjelic-Radisic, Prof. Dr.
Vesna Bjelic-Radisic, Prof. Dr.
About this study
Official title: 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).
Read the 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.
- Conditions
- HER2-positive Early Breast Cancer
- Being tested
- Trastuzumab deruxtecan, Standard-of-Care
- Keywords
- HER2+, T-DXd, Trastuzumab-deruxtecan, pCR, intermediate risk, high risk, low risk, recurrence, neoadjuvant
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab deruxtecanDrug
Also called ENHERTU
T-DXd i.v.
Standard-of-CareDrug
Also called Chemotherapy+T+P
Chemotherapy+T+P
| Study group | Role | What they receive |
|---|---|---|
| T-DXd 12 weeks: 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 Receives: Drug: Trastuzumab deruxtecan |
| T-DXd 18 weeks: 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 Receives: Drug: Trastuzumab deruxtecan |
| Control SoC CTx 12 weeks: 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 Receives: Drug: Standard-of-Care |
| Control SoC CTx 18 weeks: 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 Receives: Drug: Standard-of-Care |
| T-DXd 12 weeks + SoC CTx 6 weeks | Experimental | 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) Receives: Drug: Trastuzumab deruxtecan; Drug: Standard-of-Care |
| T-DXd 12 weeks + SoC CTx 12 weeks | Experimental | 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) Receives: Drug: Trastuzumab deruxtecan; Drug: Standard-of-Care |
| SoC CTx 18 weeks | 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
* 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). Receives: Drug: Standard-of-Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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)
Measured: after 18 weeks of neoadjuvant treatment
distant disease-free survival (dDFS, according to STEEP 2.0 criteria): T-DXd
dDFS in patients with T-DXd neoadjuvant monotherapy (pooled experimental treatment arms of part 1, pooled cohorts 1 and 2)
Measured: after 3 years
distant disease-free survival (dDFS, according to STEEP 2.0 criteria): CTx
in patients with T-DXd neoadjuvant therapy followed by CHT (pooled experimental treatment arms of part 2, cohort 3)
Measured: after 3 years
pCR rate after 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)
Measured: after 18 weeks of neoadjuvant treatment
Secondary outcomes (33)
distant disease-free survival (dDFS, according to STEEP 2.0 criteria): 18 weeks
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)
Measured: after 3 years
distant disease-free survival (dDFS, according to STEEP 2.0 criteria): 12 weeks
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)
Measured: after 3 years
distant disease-free survival (dDFS, according to STEEP 2.0 criteria): 12 plus 6 weeks
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)
Measured: after 3 years
distant disease-free survival (dDFS, according to STEEP 2.0 criteria): 12 plus 12 weeks
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)
Measured: after 3 years
distant disease-free survival (dDFS, according to STEEP 2.0 criteria)
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)
Measured: after 3 years
pCR rate: 18 weeks
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)
Measured: after 18 weeks treatment
pCR rate: 12 weeks
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)
Measured: after 12 weeks treatment
pCR rate: 12 plus 12 weeks
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)
Measured: after 24 weeks treatment
Clinical response after 6 weeks
defined as either cCR, cPR, cSD, after 6 weeks of neoadjuvant treatment compared between T-DXd treated patients and SoC treated patients
Measured: after 6 weeks treatment
Clinical response after 12 weeks
defined as either cCR, cPR, cSD, after 12 weeks of neoadjuvant treatment compared between T-DXd treated patients and SoC treated patients
Measured: after 12 weeks treatment
Clinical response after 24 weeks
defined as either cCR, cPR, cSD, after 24 weeks of neoadjuvant treatment compared between T-DXd treated patients and SoC treated patients
Measured: after 24 weeks treatment
iDFS
survival endpoint STEEP 2.0
Measured: at end of study
OS
survival endpoint STEEP 2.0
Measured: at end of study
LRFS
survival endpoint STEEP 2.0
Measured: at end of study
BCFS
survival endpoint STEEP 2.0
Measured: at end of study
DRFI
survival endpoint STEEP 2.0
Measured: at end of study
QOL
health-related quality of life
Measured: after 1 year
adverse drug reaction with CTCAE-grade 3 or higher: 12 weeks mono
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)
Measured: after 12 weeks treatment
adverse drug reaction with CTCAE-grade 3 or higher: 18 weeks combined
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)
Measured: after 18 weeks treatment
adverse drug reaction with CTCAE-grade 3 or higher: 24 weeks combined
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)
Measured: after 24 weeks treatment
Proportion of patients with any TEAE: 18 weeks mono
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)
Measured: after 18 weeks treatment
Proportion of patients with any TEAE: 12 weeks mono
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)
Measured: after 12 weeks treatment
Proportion of patients with any TEAE: 18 weeks combined
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)
Measured: after 18 weeks treatment
Proportion of patients with any TEAE: 24 weeks combined
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)
Measured: after 24 weeks treatment
Frequency of TEAE: 12 weeks
in all T-DXd based neoadjuvant treatment regimens as well as in SoC for 12 weeks (part 1, cohort 1)
Measured: after 12 weeks treatment
Frequency of TEAE : 18 weeks
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)
Measured: after 18 weeks treatment
Proportion of patients with adverse event of special interest (AESI): 18 weeks mono
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)
Measured: after 18 weeks treatment
Proportion of patients with adverse event of special interest (AESI): 12 weeks mono
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 )
Measured: after 12 weeks treatment
Proportion of patients with adverse event of special interest (AESI): 18 weeks combined
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)
Measured: after 18 weeks treatment
Proportion of patients with adverse event of special interest (AESI): 24 weeks combined
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)
Measured: after 24 weeks treatment
Frequency of AESI in T-DXd
in all four T-DXd based neoadjuvant treatment regimens
Measured: after 12 weeks treatment
Frequency of AESI in SoC: 12 weeks
in SoC for 12 weeks (part 1, cohort 1)
Measured: after 12 weeks treatment
Frequency of AESI in SoC: 18 weeks
in SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
Measured: after 18 weeks treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study start5 Feb 2024
- Primary completionJun 2030 (estimated)
- Study completionSep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-positive Early Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 702 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Women's Cancer Study Group GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Nadia Harbeck, Prof. Dr., Principal investigator, Breast Centre, Dept. Obstetrics & Gynaecology and CCC Munich LMU University HospitalSherko Kuemmel, PRof. Dr., Principal investigator, Breast Centre, Kliniken Essen Mitte EssenOleg Gluz, PD Dr., Principal investigator, Breast Centre, Evang. Bethesda-Hospital MoenchengladbachMichael Braun, Prof. Dr., Principal investigator, Breast Centre Rotkreuzklinikum MunichMonika Graeser, PD Dr., Principal investigator, Breast Centre, Evang. Bethesda-Hospital Moenchengladbach
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05704829
- Sponsor's protocol ID
- WSG-AM12 (ADAPT-HER2-IV)
- Acronym
- ADAPTHER2-IV
- Status last verified
- Jun 2026
- First submitted
- 28 Dec 2022
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No