A Phase 3 interventional study of Trastuzumab Deruxtecan and Paclitaxel in Breast Neoplasms, Breast Cancer and HER2-positive Early Breast Cancer, sponsored by AstraZeneca. Active, not recruiting at 145 sites in 18 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-11.
Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment
This study will look at the efficacy and safety of trastuzumab deruxtecan (T-DXd) in a neoadjuvant setting, in high-risk, HER2-positive early non-metastatic breast cancer.
The target population of interest in this study is participants with high-risk HER2-positive early-stage breast cancer. The purpose of this study is to determine the efficacy and safety of T-DXd neoadjuvant therapy.
Participants will be randomised to one of 3 arms: T-DXd monotherapy (Arm A), T-DXd followed by THP (Arm B), or ddAC-THP (Arm C).
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 927 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.
Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Exclusion Criteria:
Trastuzumab deruxtecan
Drug: Trastuzumab Deruxtecan
T-DXd, followed by THP
Drug: Trastuzumab Deruxtecan · Drug: Paclitaxel · Drug: Trastuzumab · Drug: Pertuzumab
doxorubicin and cyclophosphamide, followed by THP
Drug: Paclitaxel · Drug: Trastuzumab · Drug: Pertuzumab · Drug: Doxorubicin · Drug: cyclophosphamide
administered by intravenous infusion
Also known as: T-DXd, Enhertu
administered by intravenous infusion
Also known as: Taxol, Onxol
administered by intravenous infusion
Also known as: Herceptin, Herzuma
administered by intravenous infusion
Also known as: Perjeta
administered by intravenous infusion
Also known as: Adriamycin, Rubex
administered by intravenous infusion
Also known as: Neosar, Cytoxan
Rate of Pathologic Complete Response (pCR).
Proportion of participants who have no evidence by Hematoxylin \& Eosin (H\&E) staining of residual invasive disease in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by central evaluation following completion of neoadjuvant therapy.
Time frame: Through to definitive surgery or discontinuation/withdrawal from study, up to a maximum of approximately 40 months from randomization to primary pCR DCO (12MAR2025)
Event-Free Survival (Count)
Event-free survival (EFS) is defined as the time from date of randomization until disease progression precluding initial surgery, invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause.
Time frame: Up to a maximum of approximately 65 months from randomization to EFS final analysis DCO (Apr 2027)
Event-Free Survival (Duration)
Event-free survival (EFS) is defined as the time from date of randomization until disease progression precluding initial surgery, invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause.
Time frame: Up to a maximum of approximately 65 months from randomization to EFS final analysis DCO (Apr 2027)
The study is active, not recruiting and conducted in 18 countries worldwide across 147 centres, with 927 patients who were randomized up until 24th April 2024. Results are reported for the study at the data cut-off for the primary analysis for pathologic complete response (pCR) on 12th March 2025.
| Milestone | Arm A | Arm B | Arm C |
|---|---|---|---|
| Started | 286 | 321 | 320 |
| Completed | 0 | 0 | 0 |
| Not completed | 286 | 321 | 320 |
| Withdrew: Death | 8 | 3 | 9 |
| Withdrew: Withdrawal by subject | 11 | 4 | 21 |
| Withdrew: As recorded on the case report form (crf). | 1 | 1 | 2 |
| Withdrew: Ongoing at the time of primary analysis for pcr | 266 | 313 | 288 |
Proportion of participants who have no evidence by Hematoxylin \& Eosin (H\&E) staining of residual invasive disease in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by central evaluation following completion of neoadjuvant therapy.
| Percentage of participants | Arm A | Arm B | Arm C |
|---|---|---|---|
| Rate of Pathologic Complete Response (pCR). | 43.01 | 67.29 | 56.25 |
Event-free survival (EFS) is defined as the time from date of randomization until disease progression precluding initial surgery, invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause.
Results for this outcome have not been posted.
Event-free survival (EFS) is defined as the time from date of randomization until disease progression precluding initial surgery, invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause.
Results for this outcome have not been posted.
Collected over All-cause mortality: from date of randomization through to death due to any cause. Adverse events and SAEs are reported from the first dose date, throughout the treatment period and the safety follow-up period (until 40 + 7 days after the discontinuation of all study interventions). Both up to a maximum of approximately 40 months to primary pCR DCO (12MAR2025).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| T-DXd | 8/286 (2.8%) | 29/283 (10.2%) | 269/283 (95.1%) |
| T-DXd-THP | 3/321 (0.9%) | 34/320 (10.6%) | 306/320 (95.6%) |
| ddAC-THP | 9/320 (2.8%) | 63/312 (20.2%) | 307/312 (98.4%) |
| Event | T-DXd | T-DXd-THP | ddAC-THP |
|---|---|---|---|
| PneumoniaInfections and infestations | 3/283 | 1/320 | 9/312 |
| PneumonitisRespiratory, thoracic and mediastinal disorders | 1/283 | 4/320 | 7/312 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/283 | 1/320 | 7/312 |
| AnaemiaBlood and lymphatic system disorders | 1/283 | 0/320 | 5/312 |
| MyelosuppressionBlood and lymphatic system disorders | 0/283 | 0/320 | 5/312 |
| NeutropeniaBlood and lymphatic system disorders | 0/283 | 0/320 | 5/312 |
| PyrexiaGeneral disorders | 0/283 | 2/320 | 4/312 |
| Covid-19Infections and infestations | 3/283 | 3/320 | 3/312 |
| Alanine aminotransferase increasedInvestigations | 0/283 | 2/320 | 3/312 |
| Aspartate aminotransferase increasedInvestigations | 0/283 | 0/320 | 3/312 |
| Event | T-DXd | T-DXd-THP | ddAC-THP |
|---|---|---|---|
| NauseaGastrointestinal disorders | 193/283 | 207/320 | 161/312 |
| DiarrhoeaGastrointestinal disorders | 64/283 | 187/320 | 168/312 |
| AlopeciaSkin and subcutaneous tissue disorders | 120/283 | 152/320 | 153/312 |
| AnaemiaBlood and lymphatic system disorders | 42/283 | 73/320 | 152/312 |
| ConstipationGastrointestinal disorders | 95/283 | 93/320 | 76/312 |
| VomitingGastrointestinal disorders | 87/283 | 91/320 | 66/312 |
| StomatitisGastrointestinal disorders | 39/283 | 59/320 | 86/312 |
| FatigueGeneral disorders | 66/283 | 74/320 | 82/312 |
| Neuropathy peripheralNervous system disorders | 11/283 | 83/320 | 65/312 |
| Alanine aminotransferase increasedInvestigations | 63/283 | 77/320 | 80/312 |
This population includes all randomized patients.
| Age, Categorical(Participants) | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 252 | 282 | 288 | 822 |
| >=65 years | 34 | 39 | 32 | 105 |
| Age, Continuous(Years) | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|
| Mean | 50.3 ± 11.25 | 50.0 ± 11.09 | 50.1 ± 11.32 | 50.1 ± 11.21 |
| Sex: Female, Male(Participants) | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|
| Female | 286 | 321 | 320 | 927 |
| Male | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|
| Hispanic or Latino | 28 | 29 | 28 | 85 |
| Not Hispanic or Latino | 257 | 292 | 292 | 841 |
| Unknown or Not Reported | 1 | 0 | 0 | 1 |
| Race/Ethnicity, Customized(Participants) | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|
| Black or African American | 7 | 5 | 7 | 19 |
| Native Hawaiian or other Pacific Islander | 0 | 1 | 1 | 2 |
| American Indian or Alaska Native | 2 | 2 | 0 | 4 |
| Asian | 127 | 160 | 157 | 444 |
| White | 139 | 140 | 137 | 416 |
| Other | 6 | 9 | 9 | 24 |
| Not reported | 5 | 4 | 9 | 18 |
| Height(cm) | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|
| Mean | 160.248 ± 7.0934 | 159.793 ± 6.8713 | 160.441 ± 7.1728 | 160.158 ± 7.0434 |
| Weight(kg) | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|
| Mean | 66.212 ± 15.2465 | 64.879 ± 12.3807 | 66.284 ± 14.5867 | 65.776 ± 14.0814 |
| BMI(kg/m2) | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|
| Mean | 25.717 ± 5.3100 | 25.383 ± 4.6143 | 25.724 ± 5.2130 | 25.604 ± 5.0432 |
2 further baseline measures are reported on the registry.
Showing the first 100 of 145 sites across 18 countries.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient data from AstraZeneca Group of Companies, sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ Disclosure Commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Supporting information: Study protocol, Sap
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