TriangleNCT03529110 · CITED IN SOURCE DOCUMENTS
DS-8201a Versus T-DM1 for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [DESTINY-Breast03]
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2025-10-21
This study is designed to compare the anti-tumor activity as well as the safety and efficacy of DS-8201a versus T-DM1 in HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
Overall Survival (OS) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
Percentage of Participants With Objective Response Rate (ORR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
Duration of Response (DoR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
Progression-Free Survival (PFS) Based on Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: 1. Must be competent and able to comprehend, sign, and date an Institutional Review Board (IRB) or Ethics Committee (EC) approved ICF before performance of any study-specific procedures or tests. 2. Adults ≥18 y old. (Please follow local regulatory requirements if the legal age of consent for study participation is \>18 y old.) 3. Pathologically documented breast cancer that: 1. is unresectable or metastatic. 2. has confirmed HER2-positive expression as determined according to American Society of Clinical Oncology - College of American Pathologists guidelines evaluated at a central laboratory.23 3. was previously treated with trastuzumab and taxane in the advanced/ metastatic setting or progressed within 6 mo after neoadjuvant or adjuvant treatment involving a regimen including trastuzumab and taxane. 4. Documented radiologic progression (during or after most recent treatment or within 6 mo after completing adjuvant therapy). 5. Subjects must be HER2-positive as confirmed by central laboratory assessment of most recent tumor tissue sample available. If archived tissue is not available, a fresh biopsy is required. 6. Presence of at least 1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1 Exclusion Criteria: 1. Prior treatment with an anti-HER2 ADC (such as T-DM1) in the metastatic setting. Prior treatment in the adjuvant/neoadjuvant setting would be allowed if progression of disease did not occur within 12 mo of end of adjuvant therapy. 2. Uncontrolled or significant cardiovascular disease, including any of the following: 1. History of myocardial infarction within 6 mo before randomization; 2. History of symptomatic congestive heart failure (New York Heart Association Class II to IV); 3. Troponin levels consistent with myocardial infarction as defined according to the manufacturer within 28 d prior to randomization; 4. Corrected QT interval (QTc) prolongation to \> 470 ms (females) or \>450 ms (male) based on average of Screening triplicate 12-lead ECG; 5. LVEF \< 50% within 28 d prior to randomization 3. Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening. 4. Spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. * Subjects with clinically inactive brain metastases may be included in the study. * Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 wk must have elapsed between the end of whole brain radiotherapy and study enrollment. 5. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product. 6. History of severe hypersensitivity reactions to other mAbs.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).
- intervention Names
- Drug: Trastuzumab deruxtecan (T-DXd)
- label
- Trastuzumab deruxtecan (T-DXd)
- type
- EXPERIMENTAL
- description
- Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.
- intervention Names
- Drug: Ado-trastuzumab emtansine (T-DM1)
- label
- Ado-trastuzumab emtansine (T-DM1)
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Trastuzumab deruxtecan (T-DXd)
- description
- T-DXd is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously.
- name
- Trastuzumab deruxtecan (T-DXd)
- other Names
- DS-8201a
- type
- DRUG
- arm Group Labels
- Ado-trastuzumab emtansine (T-DM1)
- description
- The treatment will be in accordance with the approved label.
- name
- Ado-trastuzumab emtansine (T-DM1)
- other Names
- T-DM1
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 524
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Progression-free survival (PFS) by BICR was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
- measure
- Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
- time Frame
- Up to 33 months (data cut-off)
- secondary Outcomes
- description
- Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause.
- measure
- Overall Survival (OS) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
- time Frame
- Up to 33 months (data cut-off)
- description
- The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by BICR and investigator assessment based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR is reported.
- measure
- Percentage of Participants With Objective Response Rate (ORR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
- time Frame
- Up to 33 months (data cut-off)
- description
- Duration of Response (DoR) was defined as the time from the date of the first documentation of objective response (complete response \[CR\] or partial response \[PR\]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR in participants with confirmed CR/PR based on BICR and investigator assessment is reported.
- measure
- Duration of Response (DoR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
- time Frame
- Up to 33 months (data cut-off)
- description
- Progression-free survival (PFS) by investigator assessment was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
- measure
- Progression-Free Survival (PFS) Based on Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
- time Frame
- Up to 33 months (data cut-off)
Full study description
- brief Summary
- This study is designed to compare the anti-tumor activity as well as the safety and efficacy of DS-8201a versus T-DM1 in HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane.
Source references
- references
- citation
- Iwata H, Xu B, Kim SB, Chung WP, Park YH, Kim MH, Tseng LM, Chung CF, Huang CS, Kim JH, Chiu JWY, Yamashita T, Li W, Egorov A, Nishijima S, Nakatani S, Nishiyama Y, Sugihara M, Cortes J, Im SA. Trastuzumab deruxtecan versus trastuzumab emtansine in Asian patients with HER2-positive metastatic breast cancer. Cancer Sci. 2024 Sep;115(9):3079-3088. doi: 10.1111/cas.16234. Epub 2024 Jul 9.
- pmid
- 38979893
- type
- DERIVED
- citation
- Cortes J, Hurvitz SA, Im SA, Iwata H, Curigliano G, Kim SB, Chiu JWY, Pedrini JL, Li W, Yonemori K, Bianchini G, Loi S, Borges GS, Wang X, Bachelot T, Nakatani S, Ashfaque S, Liang Z, Egorov A, Hamilton E. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial. Nat Med. 2024 Aug;30(8):2208-2215. doi: 10.1038/s41591-024-03021-7. Epub 2024 Jun 2.
- pmid
- 38825627
- type
- DERIVED
- citation
- Ma R, Shi Y, Yan R, Yin S, Bu H, Huang J. Efficacy and safety of trastuzumab deruxtecan in treating human epidermal growth factor receptor 2-low/positive advanced breast cancer:A meta-analysis of randomized controlled trials. Crit Rev Oncol Hematol. 2024 Apr;196:104305. doi: 10.1016/j.critrevonc.2024.104305. Epub 2024 Mar 3.
- pmid
- 38442809
- type
- DERIVED
- citation
- Cortes J. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer: a plain language summary of the DESTINY-Breast03 study. Future Oncol. 2024 Feb;20(4):167-178. doi: 10.2217/fon-2023-0422. Epub 2023 Dec 7.
- pmid
- 38059424
- type
- DERIVED
- citation
- Rugo HS, Crossno CL, Gesthalter YB, Kelley K, Moore HB, Rimawi MF, Westbrook KE, Buys SS. Real-World Perspectives and Practices for Pneumonitis/Interstitial Lung Disease Associated With Trastuzumab Deruxtecan Use in Human Epidermal Growth Factor Receptor 2-Expressing Metastatic Breast Cancer. JCO Oncol Pract. 2023 Aug;19(8):539-546. doi: 10.1200/OP.22.00480. Epub 2023 May 19.
- pmid
- 37207306
- type
- DERIVED
- citation
- Curigliano G, Dunton K, Rosenlund M, Janek M, Cathcart J, Liu Y, Fasching PA, Iwata H. Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Ann Oncol. 2023 Jul;34(7):569-577. doi: 10.1016/j.annonc.2023.04.516. Epub 2023 May 12.
- pmid
- 37179020
- type
- DERIVED
- citation
- Hurvitz SA, Hegg R, Chung WP, Im SA, Jacot W, Ganju V, Chiu JWY, Xu B, Hamilton E, Madhusudan S, Iwata H, Altintas S, Henning JW, Curigliano G, Perez-Garcia JM, Kim SB, Petry V, Huang CS, Li W, Frenel JS, Antolin S, Yeo W, Bianchini G, Loi S, Tsurutani J, Egorov A, Liu Y, Cathcart J, Ashfaque S, Cortes J. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2023 Jan 14;401(10371):105-117. doi: 10.1016/S0140-6736(22)02420-5. Epub 2022 Dec 7.
- pmid
- 36495879
- type
- DERIVED
- citation
- Rugo HS, Bianchini G, Cortes J, Henning JW, Untch M. Optimizing treatment management of trastuzumab deruxtecan in clinical practice of breast cancer. ESMO Open. 2022 Aug;7(4):100553. doi: 10.1016/j.esmoop.2022.100553. Epub 2022 Aug 11.
- pmid
- 35964548
- type
- DERIVED
- citation
- Cortes J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Huang CS, Kim JH, Chiu JWY, Pedrini JL, Lee C, Liu Y, Cathcart J, Bako E, Verma S, Hurvitz SA; DESTINY-Breast03 Trial Investigators. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. doi: 10.1056/NEJMoa2115022.
- pmid
- 35320644
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-4a75a4b0f6d4f16d0cf9
- requested nct id
- NCT03529110
- primary nct id
- NCT03529110
- source kind
- fda_spl_label
- source record id
- a4106ba4-f398-4663-980c-2b7195283edd
- source file sha256
- 424ccf5bc67db0a96ee2c35ed913dd5894642716182773d81ca19cdfb9ba32f3
- payload sha256
- 89c46f07c9eddcdd45ba726d4951fce1bb99ca2b009d981b38a5e5d317cfc912
- payload
- application numbers
- BLA761139
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-4a75a4b0f6d4f16d0cf9
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT03529110
- occurrences
- context exact
- se, % 72 73 Figure 2: Kaplan-Meier Plot of Progression-Free Survival per BICR DESTINY-Breast03 The efficacy of ENHERTU was evaluated in study DESTINY-Breast03 (NCT03529110), a multicenter, open-label, randomized trial that enrolled 524 patients with HER2-positive, unresectable and/or metastatic breast cancer who received prior tr
- end
- 11673
- exact text
- NCT03529110
- start
- 11662
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00500.json
- source file sha256
- 424ccf5bc67db0a96ee2c35ed913dd5894642716182773d81ca19cdfb9ba32f3
- source json pointer
- /results/82/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- a4106ba4-f398-4663-980c-2b7195283edd
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 2a5c82cae51b76ab795b3709725fbbf87538a8fd70e4f14e653fb5a6a43bfd0a
- spl effective time
- 20260515
- spl set id
- 7e67e73e-ddf4-4e4d-8b50-09d7514910b6
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-e86970576b30ca5a45be
- requested nct id
- NCT03529110
- primary nct id
- NCT03529110
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source file sha256
- 862f78faa9e4cbedc19f9ffcaeba97e029ba51b72bb3b81fc67aa8b6adf96904
- payload sha256
- 7f1b97df78ba6ef4437ddf558df4dd1c8c3baddf97660286d4f0ba008326c796
- payload
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-e86970576b30ca5a45be
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT03529110
- occurrences
- context exact
- mab deruxtecan):</p> <div class="pdq-content-list"><ol id="_2217"><li> A phase III, multicenter, open-label, randomized trial (<a href="/clinicaltrials/NCT03529110">DESTINY-Breast03</a> [NCT03529110]) compared the efficacy and safety of trastuzumab deruxtecan with trastuzumab emtansine. The study included 524 patients wit
- end
- 635984
- exact text
- NCT03529110
- start
- 635973
- context exact
- lass="pdq-content-list"><ol id="_2217"><li> A phase III, multicenter, open-label, randomized trial (<a href="/clinicaltrials/NCT03529110">DESTINY-Breast03</a> [NCT03529110]) compared the efficacy and safety of trastuzumab deruxtecan with trastuzumab emtansine. The study included 524 patients with HER2-positive metastatic breast c
- end
- 636019
- exact text
- NCT03529110
- start
- 636008
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/nci/raw/29bf1e5a1d739974ed.html
- source file sha256
- 862f78faa9e4cbedc19f9ffcaeba97e029ba51b72bb3b81fc67aa8b6adf96904
- source json pointer
- Source null
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source retrieved at
- 2026-09-09T23:21:35.419733+00:00
- source string basis
- UTF-8_text_with_universal_newline_translation
- source string sha256
- 536430925e3b0008edd3fb69a869d5645bd6b6dc5c84c21ddf1b3e24f089874c
- source title
- Breast Cancer Treatment (PDQ®)–Health Professional Version
- source update dates
- context
- Updated: April 25, 2025
- datetime
- 2025-04-25T12:00:00Z
- display
- April 25, 2025
Preserved source evidence · Not medical advice