Breast Cancer; HER2-positive; MetastaticPhase 3NCT04784715
Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer (DESTINY-Breast09)
A Phase 3 study testing Trastuzumab deruxtecan, Taxane and Pertuzumab in people with Breast Cancer; HER2-positive; Metastatic, run by AstraZeneca at 283 sites in 27 countries.
Trial summary
The study will evaluate the efficacy and safety of trastuzumab deruxtecan (also known as T-DXd, DS-8201a), either alone or in combination with pertuzumab, in treating patients with Human epidermal growth factor receptor 2 (HER2)-positive breast cancer as a first line of treatment in the metastatic setting. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Breast Cancer; HER2-positive; Metastatic
- What is being tested?
- Trastuzumab deruxtecan, Taxane and Pertuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,157 participants
- Where
- 283 sitesin 27 countries
- Study dates
- 26 Apr 2021to 31 Dec 2029
- Phase
- Phase 3
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 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be ≥18 years of age
- Pathologically documented breast cancer that:
- is advanced or metastatic
- is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+ or ISH+)
- is documented by local testing as hormone receptor (HR)-positive or HR-negative disease in the metastatic setting
- No prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer or only 1 previous line of endocrine therapy in the metastatic setting. Participants who have received chemotherapy or HER2-targeted therapy in the neo-adjuvant or adjuvant setting are eligible if > 6 months from treatment to metastatic diagnosis.
- Has protocol-defined adequate organ and bone marrow function
- ECOG performance status 0 or 1
Who cannot join
- Ineligible for any of the agents on the study.
- Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with subject's participation or study results
- Patients with spinal cord compression or clinically active central nervous system metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic may be included in the study.
- Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
- Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
Trial locations and contacts
283 sites in 27 countries.
283 sites in 27 countries
China34 sites
Research Site
Beijing, 100039
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Beijing, 100044
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Beijing, 100191
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Changchun, 130021
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Changsha, 410008
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Changsha, 410013
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Chengdu, 610041
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Chongqing, 400016
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Chongqing, 400030
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Dalian, 116011
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Guangzhou, 510060
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Guangzhou, 510080
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Guangzhou, 510120
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Hangzhou, 310003
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Hangzhou, 310022
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Harbin, 150049
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Kunming, 650118
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Nanchang, 330009
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Nanjing, 210008
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Nanjing, 210029
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Nanning, 530021
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Qingdao, 266100
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Shanghai, 200025
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Shanghai, 200032
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Shenyang, 110001
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Shenzhen, 518036
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Tianjin, 300060
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Wuhan, 430022
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Wuhan, 430030
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Wuhan, 430060
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Xi'an, 710004
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Xi'an, 710061
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Yinchuan, 750004
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Zhengzhou, 450008
Japan32 sites
Research Site
Akashi-shi, 673-8558
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Aomori, 030-8553
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Bunkyō City, 113-8431
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Chiba, 260-8717
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Chūōku, 104-0045
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Fukushima, 960-1295
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Hidaka-shi, 350-1298
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Hiroshima, 730-8518
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Hiroshima, 734-8551
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Isehara-shi, 259-1193
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Kagoshima, 892-0833
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Kawasaki-shi, 216-8511
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Kobe, 650-0047
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Kōtoku, 135-8550
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Kurume-shi, 830-0011
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Kyoto, 606-8507
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Matsuyama, 791-0280
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Nagoya, 464-8681
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Nagoya, 467-8602
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Niigata, 951-8566
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Nishinomiya-shi, 663-8501
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Okayama, 700-8558
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Osaka, 541-8567
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Ota-shi, 373-8550
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Sapporo, 003-0804
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Sendai, 980-8574
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Shinagawa-ku, 142-8666
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Shinjuku-ku, 160-0023
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Shinjuku-ku, 162-8655
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Shizuoka, 420-8527
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Tsu, 514-8507
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Yokohama, 241-8515
United States30 sites
Research Site
Atlanta, Georgia, 30318
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Boston, Massachusetts, 02215
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Dallas, Texas, 75203
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Dallas, Texas, 75246
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Denton, Texas, 76201
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Detroit, Michigan, 48202
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Germantown, Tennessee, 38138
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Glendale, California, 91204
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Glendale, California, 91206
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Houston, Texas, 77090
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Jackson, Mississippi, 39213
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Las Vegas, Nevada, 89128
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Longmont, Colorado, 80501
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Louisville, Kentucky, 40241
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Miami, Florida, 33176
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New York, New York, 10065
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Norfolk, Virginia, 23502
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Palm Bay, Florida, 32909
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Plantation, Florida, 33324
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Roanoke, Virginia, 24014
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San Antonio, Texas, 78240
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Shenandoah, Texas, 77380
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Shirley, New York, 11967
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Silver Spring, Maryland, 20904
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Springdale, Arkansas, 72762
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Summit, New Jersey, 07901
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Tacoma, Washington, 98405
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Tucson, Arizona, 85711
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Tyler, Texas, 75702
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York, Pennsylvania, 17403
France15 sites
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Avignon, 84000
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Besançon, 25000
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Bordeaux, 33030
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Caen, 14076
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Le Mans, 72000
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Montpellier, 34070
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Montpellier, 34298
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Nice, 06189
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Paris, 75005
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Pierre-Bénite, 69495
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Rennes, 35042
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Saint-Cloud, 92210
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Saint-Herblain, 44805
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Toulouse, 31059
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Vandœuvre-lès-Nancy, 54519
Canada13 sites
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Barrie, Ontario, L4M 6M2
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Calgary, Alberta, T2N 5G2
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Halifax, Nova Scotia, B3H 2Y9
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Kitchener, Ontario, N2G 1G3
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Montreal, Quebec, H1T 2M4
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Montreal, Quebec, H2X 3E4
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Montreal, Quebec, H3T 1M5
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Montreal, Quebec, H4A 3J1
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Newmarket, Ontario, L3Y 2P9
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North York, Ontario, M2K 1E1
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Saskatoon, Saskatchewan, S7N 4H4
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Ste-Foy, Quebec, G1V 4G2
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Toronto, Ontario, M5G 1X5
Argentina12 sites
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Buenos Aires, C1125ABD
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Caba, C1118AAT
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CABA, 1414
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CABA, C1012AAR
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Capital Federal, C1417DTB
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Cipolletti, 8234
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Ciudad de Buenos Aires, 1280
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La Plata, 1900
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Mar del Plata, 7600
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Rosario, S2000DEJ
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Rosario, S2002KDS
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San Salvador de Jujuy, 4600
Germany11 sites
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Berlin, 10117
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Dresden, 1307
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Erlangen, 91054
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Essen, 45136
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Frankfurt am Main, 60431
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Freiburg im Breisgau, 79110
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Hamburg, 20357
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Heidelberg, 69120
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Leipzig, 04103
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Münster, 48149
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Paderborn, 33161
India10 sites
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Ahmedabad, 380060
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Bangalore, 560027
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Bengaluru, 560099
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Calicut, 673601
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Gūrgaon, 122001
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Mysuru, 570017
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Nashik, 422009
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Nashik, 422011
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New Delhi, 110075
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New Delhi, 110085
South Korea10 sites
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Cheonan-si, 31151
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Daegu, 41404
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Goyang-si, 10408
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Seoul, 03080
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Seoul, 03722
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Seoul, 05505
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Seoul, 06273
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Seoul, 06351
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Seoul, 06591
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Seoul, 08308
Brazil9 sites
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Florianópolis, 88034-000
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Goiânia, 74000-000
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Londrina, 86015-520
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Natal, 59075-740
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Porto Alegre, 90035-003
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Ribeirão Preto, 14015-130
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São Paulo, 03102-002
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Sorocaba, 18030-005
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Vitória, 29043-260
Hungary9 sites
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Budapest, 1062
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Budapest, 1082
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Budapest, 1115
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Budapest, 1122
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Budapest, 1145
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Győr, 9024
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Kecskemét, 6000
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Nyíregyháza, 4400
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Szolnok, 5000
Italy9 sites
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Bergamo, 24127
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Candiolo, 10060
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Genova, 16132
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Livorno, 57100
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Milan, 20141
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Naples, 80131
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Padova, 35128
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Rozzano, 20089
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Udine, 33100
South Africa9 sites
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Cape Town, 7570
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Cape Town, 7925
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George, 6529
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Johannesburg, 2193
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Johannesburg, 2196
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Port Elizabeth, 6045
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Pretoria, 0081
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Rondebosch, 7700
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Soweto, 2013
Belgium8 sites
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Brussels, 1160
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Brussels, 1200
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Charleroi, 6060
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Edegem, 2650
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Ghent, 9000
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Leuven, 3000
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Liège, 4000
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Namur, 5000
Spain8 sites
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Alicante, 03010
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Barcelona, 08028
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Barcelona, 08036
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Barcelona, 8035
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Madrid, 28041
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Madrid, 28046
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Majadahonda, 28222
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Seville, 41009
Philippines7 sites
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Baguio City, 2600
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Cebu City, 6000
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Davao City, 8000
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Iloilo City, 5000
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Manila, 1000
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Quezon City, 1112
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San Juan City, 1500
Taiwan7 sites
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Taichung, 40443
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Tainan, 70403
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Taipei, 100
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Taipei, 10449
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Taipei, 11217
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Taipei, 235
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Taoyuan, 333
United Kingdom7 sites
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Edinburgh, EH4 2XU
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Guildford, GU2 7WG
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London, EC1A 7BE
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London, NW1 2PG
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Manchester, M20 4BX
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Swansea, SA2 8QA
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Taunton, TA1 5DA
Mexico6 sites
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Alc. Cuauhtémoc, 06700
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Estado de México, 50080
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Guadalajara, 44680
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Metepec, 52140
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Nuevo León, 66278
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Veracruz, 91910
Russia6 sites
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Moscow, 121205
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Moscow, 129090
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Moscow, 143442
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Saint Petersburg, 190020
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Saint Petersburg, 197758
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Yaroslavl, 150054
Turkey (Türkiye)6 sites
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Adana, 01330
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Ankara, 06520
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Ankara, 06800
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Cordaleo, 35575
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Malatya, 44280
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Samsun, 55200
Israel5 sites
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Haifa, 31096
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Jerusalem, 9112001
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Petah Tikva, 4941492
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Ramat Gan, 5266202
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Tel Aviv, 64239
Peru5 sites
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Arequipa, AREQUIPA01
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Lima, 15033
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Lima, 15036
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Lima, LIMA 29
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Lima, LIMA 34
Saudi Arabia5 sites
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Dammam, 31444
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Jeddah, 22384
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Jeddah, 23214
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Riyadh, 11211
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Riyadh, 11426
Sweden5 sites
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Gothenburg, 413 45
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Örebro, 701 85
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Stockholm, 118 83
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Uppsala, 75185
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Vaxjo, 35185
Denmark3 sites
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Copenhagen O, 2100
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Sønderborg, 6400
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Vejle, 7100
About this study
Official title: Phase III Study of Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive, First-line Metastatic Breast Cancer (DESTINY-Breast09)
The study will evaluate the efficacy and safety of trastuzumab deruxtecan (also known as T-DXd, DS-8201a), either alone or in combination with pertuzumab, in treating patients with Human epidermal growth factor receptor 2 (HER2)-positive breast cancer as a first line of treatment in the metastatic setting.
Read the detailed description
Eligible participants will be those diagnosed with HER2-positive (IHC 3+ or ISH+), metastatic breast cancer, who have received no prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer.
The study aims to evaluate the efficacy, and safety of trastuzumab deruxtecan, alone or with pertuzumab, compared with the standard of care treatment (taxane [docetaxel or paclitaxel], trastuzumab and pertuzumab). This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.
- Conditions
- Breast Cancer; HER2-positive; Metastatic
- Being tested
- Trastuzumab deruxtecan, Placebo, Taxane, Pertuzumab, Trastuzumab
- Keywords
- Breast Neoplasms; Breast Diseases; Trastuzumab; Antineoplastic Agents, Phytogenic; Anti-drug conjugate; Molecular Mechanisms of Pharmacological Action;
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis, Breast Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab deruxtecanDrug
Also called DS-8201a; T-DXd
Administered by intravenous infusion
PlaceboDrug
Administered by intravenous infusion
TaxaneDrug
Investigator's choice of docetaxel or paclitaxel administered by intravenous infusion
PertuzumabDrug
Administered by intravenous infusion
TrastuzumabDrug
Administered by intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Trastuzumab deruxtecan (T-DXd) plus pertuzumab-matching placebo Receives: Drug: Trastuzumab deruxtecan; Drug: Placebo |
| Arm B | Experimental | Trastuzumab deruxtecan (T-DXd) plus pertuzumab Receives: Drug: Trastuzumab deruxtecan; Drug: Pertuzumab |
| Arm C | Active comparator | Standard of care (Taxane (paclitaxel or docetaxel), trastuzumab, and pertuzumab) Receives: Drug: Taxane; Drug: Pertuzumab; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment
Defined as time from date of randomisation until the date of objective radiological disease progression according to Blinded Independent Central Review (BICR) using RECIST 1.1 or death by any cause.
Measured: Until progression or death, assessed up to approximately 60 months
Secondary outcomes (14)
Progression Free Survival (PFS) by Investigator assessment
Defined as time from date of randomisation until the date of objective radiological disease progression according to Investigator using RECIST 1.1 or death by any cause.
Measured: Until progression or death, assessed up to approximately 60 months
Overall Survival (OS)
OS is defined as the time from randomisation until the date of death due to any cause.
Measured: Until death, assessed up to approximately 104 months
Objective Response Rate (ORR) by BICR and Investigator assessment
ORR is defined as The proportion of participants who have a complete response (CR) or partial response (PR) based on BICR and investigator assessment using RECIST 1.1.
Measured: Until progression or death (in the absence of progression), assessed up to approximately 60 months
Duration of Response (DoR) by BICR and Investigator Assessment
DoR is defined as the time from date of first detection of objective response until the date of objective radiological disease progression according to BICR and investigator assessment using RECIST 1.1 or death in the absence of progression.
Measured: Until progression or death (in the absence of progression), assessed up to approximately 60 months
Time to second progression or death (PFS2) by Investigator assessment
PFS2 is defined as the time from randomisation until the date of tumor progression on next-line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy after the first progression) or death from any cause; second progression will be defined according to local standard clinical practice.
Measured: Assessed up to approximately 104 months
To assess the effect of T-DXd ± pertuzumab relative to THP in terms of patient-reported pain in participants with HER2 positive, first-line mBC'.
Pain progression: Time to sustained deterioration of European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Pain Scale. Scores range from 0-100 based on 2 items with responses ranging from 1-4. A lower score would mean better outcome.
Measured: Assessed up to approximately 60 months
To assess patient-reported treatment tolerability
Proportion of participants experiencing treatment related symptoms as measured by selected items from the European Organisation for Research and Treatment of Cancer, general cancer module (EORTC QLQ-C30), score of 1-4. A lower score would mean better outcome.
Measured: Assessed up to approximately 60 months
To assess patient-reported treatment tolerability
Proportion of patients reporting different levels of overall tolerability as measured by the Patient Global Impression of Treatment Tolerability (PGI-TT), score of 0-4. A lower score would mean a better outcome.
Measured: Assessed up to approximately 60 months
To assess patient-reported treatment tolerability
Proportion of participants experiencing treatment related symptoms as measured by selected items from the European Organisation for Research and Treatment of Cancer, breast cancer module (EORTC QLQ-BR45), score of 1-4. A lower score would mean better outcome.
Measured: Assessed up to approximately 60 months
To assess patient-reported treatment tolerability
Proportion of participants experiencing treatment related symptoms as measured by selected items from the Patient-Reported Outcomes- Common Terminology Criteria for Adverse Events (PRO-CTCAE). PRO-CTCAE responses are scored from 0 to 4 (or 0/1 for absent/present). A lower score would mean a better outcome.
Measured: Assessed up to approximately 60 months
To assess patient-reported treatment tolerability
The proportion of participants with maintained or improved physical function while on treatment, based on the EORTC QLQ-C30 Physical Functioning scale. Scores range from 0-100, based on 5 items with responses ranging from 1-4. A higher score would mean a better outcome.
Measured: Assessed up to approximately 60 months
Serum concentration of trastuzumab deruxtecan and pertuzumab
Determination of trastuzumab deruxtecan and pertuzumab concentrations in serum.
Measured: Up to Cycle 6, approximately Week 18; each cycle is 21 days
Immunogenicity of trastuzumab deruxtecan.
Number and percentage of participants who develop anti-drug antibody (ADA) for trastuzumab deruxtecan.
Measured: Up to follow-up period, approximately 60 months
Safety and tolerability of trastuzumab deruxtecan, alone or with pertuzumab
Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm
Measured: Assessed up to approximately 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2021
- Study start26 Apr 2021
- Primary completion3 May 2027 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer; HER2-positive; MetastaticStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Study will consist of three arms: Arm A - trastuzumab deruxtecan with pertuzumab-matching placebo Arm B - trastuzumab deruxtecan with pertuzumab Arm C - standard of care (taxane \[docetaxel or paclitaxel\], trastuzumab and pertuzumab)
- Masking
- None (open label)
- Enrolment
- 1,157 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04784715
- Sponsor's protocol ID
- D967UC00001
- Other IDs
- 2023-507904-30-00, 2020-004074-21, 2023
- Status last verified
- Oct 2026
- First submitted
- 19 Feb 2021
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
Tolaney SM, Jiang Z, Zhang Q, Barroso-Sousa R, Park YH, Rimawi MF, Saura C, Schneeweiss A, Toi M, Chae YS, Kemal Y, Chaudhari M, Sendur MAN, Yamashita T, Casalnuovo M, Danso MA, Liu J, Shetty J, Herbolsheimer P, Loibl S; DESTINY-Breast09 Trial Investigators. Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2026 Feb 5;394(6):551-562. doi: 10.1056/NEJMoa2508668. Epub 2025 Oct 29.
PubMed 41160818