Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer (DB-06)

A Phase 3, Randomized, Multi-center, Open-label Study of Trastuzumab Deruxtecan (T-DXd) Versus Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Breast Cancer Patients Whose Disease Has Progressed on Endocrine Therapy in the Metastatic Setting (DESTINY-Breast06)

This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy in human epidermal growth factor receptor (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has progressed on endocrine therapy in the metastatic setting.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced or Metastatic Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab deruxtecan; Drug: Capecitabine; Drug: Paclitaxel; Drug: Nab-Paclitaxel

Detailed Description

Eligible patients will be those patients who have had disease progression on at least 2 previous lines of endocrine therapies given for the treatment of metastatic disease or disease progression within 6 months of starting first line treatment for metastatic disease with an endocrine therapy combined with a CDK4/6 inhibitor. All patients must have historically confirmed HR positive (either estrogen receptor and/or progesterone receptor positive), HER2-low (defined as IHC2+/ISH- and IHC 1+) or HER2 IHC >0 <1+ expression, as determined by central laboratory testing results, advanced or metastatic breast cancer.

The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy. 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.

• Study Type: Interventional
• Enrollment (Actual): 866
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1125ABD
    • Research Site
  • CABA, Argentina, 1414
    • Research Site
  • CABA, Argentina, C1012AAR
    • Research Site
  • CABA, Argentina, C1019ABS
    • Research Site
  • Ciudad de Buenos Aires, Argentina, 1280
    • Research Site
  • Córdoba, Argentina, 5000
    • Research Site
  • La Plata, Argentina, 1900
    • Research Site
  • Mar del Plata, Argentina, 7600
    • Research Site
  • Rosario, Argentina, S2000DEJ
    • Research Site
  • Rosario, Argentina, S2002KDS
    • Research Site
• Australia
  • Adelaide, Australia, 5000
    • Research Site
  • Birtinya, Australia, 4575
    • Research Site
  • Darlinghurst, Australia, 2010
    • Research Site
  • Murdoch, Australia, 6150
    • Research Site
  • South Brisbane, Australia, 4101
    • Research Site
  • St Leonards, Australia, 2065
    • Research Site
  • Waratah, Australia, 2298
    • Research Site
• Austria
  • Graz, Austria, 8036
    • Research Site
  • Innsbruck, Austria, 6020
    • Research Site
• Belgium
  • Anderlecht, Belgium, 1070
    • Research Site
  • Brussels, Belgium, 1200
    • Research Site
  • Charleroi, Belgium, 6060
    • Research Site
  • Edegem, Belgium, 2650
    • Research Site
  • Ghent, Belgium, 9000
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
  • Namur, Belgium, 5000
    • Research Site
  • Roeselare, Belgium, 8800
    • Research Site
  • Sint-Niklaas, Belgium, 9100
    • Research Site
• Brazil
  • Barretos, Brazil, 14784-400
    • Research Site
  • Belo Horizonte, Brazil, 30110-022
    • Research Site
  • Natal, Brazil, 59075-740
    • Research Site
  • Porto Alegre, Brazil, 90610-000
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Rio de Janeiro, Brazil, 20560-120
    • Research Site
  • Sorocaba, Brazil, 18030-510
    • Research Site
  • São Paulo, Brazil, 04038-034
    • Research Site
  • São Paulo, Brazil, 1323001
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• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Research Site
    • Edmonton, Alberta, Canada, T6G 1Z2
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  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Research Site
  • CA
    • Toronto, CA, Canada, M5G 2M9
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  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Research Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Research Site
    • Toronto, Ontario, Canada, M5G 1X5
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  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Research Site
    • Montreal, Quebec, Canada, H3T 1E2
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    • Sherbrooke, Quebec, Canada, J1H 5N4
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• China
  • Baoding, China, 071000
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  • Beijing, China, 100044
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  • Beijing, China, 100006
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  • Changchun, China, 130021
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  • Changsha, China, 410013
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  • Changsha, China, 410008
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  • Dalian, China, 116001
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  • Foshan, China, 528000
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  • Fuzhou, China, 350011
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  • Guangzhou, China, 510120
    • Research Site
  • Guangzhou, China, 510080
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  • Guangzhou, China, 510060
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  • Hangzhou, China, 310022
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  • Hangzhou, China, 310003
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  • Hangzhou, China, 310020
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  • Harbin, China, 150081
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  • Hefei, China, 230001
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  • Jinan, China, 250001
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  • Linyi, China, 276000
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  • Nanchang, China, 330006
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  • Nanchang, China, 330009
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  • Nanjing, China, 210009
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  • Nanjing, China, 210029
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  • Nanning, China, 530021
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  • Shanghai, China, 200032
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  • Shenyang, China, 110015
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  • Tianjin, China, 300060
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  • Wuhan, China, 430079
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  • Xi'an, China, 710061
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  • Xi'an, China, 710004
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  • Zhengzhou, China, 450008
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  • Ürümqi, China, 830000
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• Denmark
  • Aalborg, Denmark, 9000
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  • Copenhagen Ø, Denmark, 2100
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  • Odense, Denmark, 5000
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  • Vejle, Denmark, 7100
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• France
  • Avignon, France, 84918
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  • Besançon, France, 25000
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  • Bordeaux, France, 33000
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  • Brest, France, 29609
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  • Caen, France, 14076
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  • Dijon, France, 21079
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  • Le Mans, France, 72000
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  • Marseille, France, 13273
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  • Montpellier, France, 34298
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  • Nice, France, 06100
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  • Paris, France, 75005
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  • Pierre-Bénite, France, 69495
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  • Plerin SUR MER, France, 22190
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  • Rennes, France, 35000
    • Research Site
  • Saint-Cloud, France, 92210
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  • Saint-Herblain, France, 44805
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  • Tours, France, 37000
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  • Villejuif, France, 94805
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• Germany
  • Berlin, Germany, 10117
    • Research Site
  • Dresden, Germany, 01307
    • Research Site
  • Freiburg im Breisgau, Germany, 79110
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  • Hanover, Germany, 30625
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  • München, Germany, 81675
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  • München, Germany, D-80336
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  • Münster, Germany, 48149
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  • Velbert, Germany, 42551
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• Hungary
  • Budapest, Hungary, 1145
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  • Budapest, Hungary, 1122
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  • Budapest, Hungary, 1062
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  • Győr, Hungary, 9024
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  • Kecskemét, Hungary, 6000
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  • Nyíregyháza, Hungary, 4400
    • Research Site
  • Szolnok, Hungary, 5000
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  • Tatabánya, Hungary, 2800
    • Research Site
• India
  • Bengaluru, India, 560099
    • Research Site
  • Calicut, India, 673601
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  • Kolkata, India, 700160
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  • Marg Jaipur, India, 302004
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  • New Delhi, India, 110 085
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  • New Delhi, India, 110017
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  • New Delhi, India, 110075
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  • New Delhi, India, 110005
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  • Surat, India, 395002
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  • Thiruvananthapuram, India, 695011
    • Research Site
• Israel
  • Haifa, Israel, 3109601
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
  • Jerusalem, Israel, 9103102
    • Research Site
  • Kfar Saba, Israel, 44281
    • Research Site
  • Petah Tikva, Israel, 49100
    • Research Site
  • Ramat Gan, Israel, 52621
    • Research Site
  • Tel Aviv, Israel, 64239
    • Research Site
• Italy
  • Aviano, Italy, 33081
    • Research Site
  • Bergamo, Italy, 24127
    • Research Site
  • Candiolo, Italy, 10060
    • Research Site
  • Cona, Italy, 44124
    • Research Site
  • Genova, Italy, 16132
    • Research Site
  • Livorno, Italy, 57124
    • Research Site
  • Messina, Italy, 98158
    • Research Site
  • Milan, Italy, 20141
    • Research Site
  • Milan, Italy, 20132
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Padua, Italy, 35128
    • Research Site
  • Parma, Italy
    • Research Site
  • Prato, Italy, 59100
    • Research Site
  • Tricase, Lecce, Italy, 73039
    • Research Site
  • Udine, Italy, 33100
    • Research Site
• Japan
  • Akashi-shi, Japan, 673-8558
    • Research Site
  • Bunkyō City, Japan, 113-8431
    • Research Site
  • Chiba, Japan, 260-8717
    • Research Site
  • Chūōku, Japan, 104-0045
    • Research Site
  • Fukuoka, Japan, 811-1395
    • Research Site
  • Gifu, Japan, 501-1194
    • Research Site
  • Hidaka-shi, Japan, 350-1298
    • Research Site
  • Hiroshima, Japan, 730-8518
    • Research Site
  • Isehara, Japan, 259-1193
    • Research Site
  • Kagoshima, Japan, 892-0833
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  • Kashiwa, Japan, 277-8577
    • Research Site
  • Kawasaki-shi, Japan, 216-8511
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  • Kitaadachi-gun, Japan, 362-0806
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  • Kōtoku, Japan, 135-8550
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  • Matsuyama, Japan, 791-0280
    • Research Site
  • Nagoya, Japan, 460-0001
    • Research Site
  • Naha, Japan, 901-0154
    • Research Site
  • Niigata, Japan, 951-8566
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  • Nishinomiya-shi, Japan, 663-8501
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  • Okayama, Japan, 700-8558
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  • Osaka, Japan, 541-8567
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  • Osakasayama-shi, Japan, 589-8511
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  • Sagamihara-shi, Japan, 252-0375
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  • Sapporo, Japan, 060-8648
    • Research Site
  • Shinagawa-ku, Japan, 142-8666
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  • Shinjuku-ku, Japan, 160-0023
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  • Shizuoka, Japan, 420-8527
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  • Tsu, Japan, 514-8507
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  • Yokohama, Japan, 241-8515
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• Mexico
  • Alc. Cuauhtémoc, Mexico, 06700
    • Research Site
  • Guadalajara Jalisco, Mexico, 44280
    • Research Site
  • Guadalajra, Mexico, 44260
    • Research Site
  • Mexico City, Mexico, 0 3100
    • Research Site
  • Mexico City, Mexico, '14080
    • Research Site
  • Mexico City, Mexico, 6760
    • Research Site
  • Monterrey, Mexico, 64460
    • Research Site
  • México, Mexico, 04700
    • Research Site
  • Nuevo León, Mexico, 66278
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Research Site
  • Breda, Netherlands, 4818 CK
    • Research Site
  • Hengelo, Netherlands, 7555 DL
    • Research Site
  • Leeuwarden, Netherlands, 8934 AD
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  • Rotterdam, Netherlands, 3015 GD
    • Research Site
  • Sittard-Geleen, Netherlands, 6162 BG
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • Research Site
  • Koszalin, Poland, 75-581
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  • Krakow, Poland, 31-501
    • Research Site
  • Lodz, Poland, 90-302
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  • Rzeszów, Poland, 35-021
    • Research Site
  • Warsaw, Poland, 02-781
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  • Wroclaw, Poland, 53-413
    • Research Site
• Portugal
  • Lisbon, Portugal, 1649-035
    • Research Site
  • Lisbon, Portugal, 1998-018
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  • Lisbon, Portugal, 1500-650
    • Research Site
• Russia
  • Krasnodar, Russia, 350040
    • Research Site
  • Moscow, Russia, 115478
    • Research Site
  • Moscow, Russia, 117997
    • Research Site
  • Moscow, Russia, 121205
    • Research Site
  • Moscow, Russia, 111123
    • Research Site
  • Saint Petersburg, Russia, 190103
    • Research Site
  • Saint Petersburg, Russia, 197758
    • Research Site
  • Saint Petersburg, Russia, 195271
    • Research Site
  • Yaroslavl, Russia, 150054
    • Research Site
• Saudi Arabia
  • Dammam, Saudi Arabia, 31444
    • Research Site
  • Jeddah, Saudi Arabia, 21423
    • Research Site
  • Jeddah, Saudi Arabia, 23214
    • Research Site
  • Riyadh, Saudi Arabia, 11426
    • Research Site
  • Riyadh, Saudi Arabia, 11525
    • Research Site
  • Riyadh, Saudi Arabia, 12713
    • Research Site
• Singapore
  • Bukit Merah, Singapore, 169610
    • Research Site
  • Singapore, Singapore, 308433
    • Research Site
  • Singapore, Singapore, 258499
    • Research Site
  • Singapore, Singapore, 119074
    • Research Site
  • Singapore, Singapore, 329563
    • Research Site
• South Korea
  • Daegu, South Korea, 41404
    • Research Site
  • Goyang-si, South Korea, 10408
    • Research Site
  • Incheon, South Korea, 22332
    • Research Site
  • Seongnam-si, South Korea, 13620
    • Research Site
  • Seoul, South Korea, 02841
    • Research Site
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 05505
    • Research Site
  • Seoul, South Korea, 06351
    • Research Site
• Spain
  • A Coruña, Spain, 15006
    • Research Site
  • Barcelona, Spain, 08035
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  • Barcelona, Spain, 08036
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  • Barcelona, Spain, 08907
    • Research Site
  • Córdoba, Spain, 14004
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  • El Palmar, Spain, 30120
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  • Madrid, Spain, 28046
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  • Madrid, Spain, 28007
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  • Madrid, Spain, 28005
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  • San Sebastián, Spain, 20014
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  • Seville, Spain, 41013
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  • Valencia, Spain, 46026
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• Sweden
  • Gothenburg, Sweden, 413 45
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  • Stockholm, Sweden, 118 83
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  • Uppsala, Sweden, 751 85
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  • Vaxjo, Sweden, 35185
    • Research Site
  • Örebro, Sweden, 701 85
    • Research Site
• Taiwan
  • Taichung, Taiwan, 40447
    • Research Site
  • Tainan, Taiwan, 70403
    • Research Site
  • Tainan, Taiwan, 710
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  • Taipei, Taiwan, 235
    • Research Site
  • Taipei, Taiwan, 10449
    • Research Site
  • Taipei, Taiwan, 11217
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  • Taipei, Taiwan, 10048
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  • Taoyuan District, Taiwan, 333
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• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
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  • Cardiff, United Kingdom, CF14 2TL
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  • Edinburgh, United Kingdom, EH4 2XR
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  • Guildford, United Kingdom
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  • Leeds, United Kingdom, LS9 7TF
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  • London, United Kingdom, SE1 9RT
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  • Manchester, United Kingdom, M20 4BX
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  • Northwood, United Kingdom, HA6 2RN
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• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Research Site
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Research Site
  • California
    • Duarte, California, United States, 91010
      • Research Site
    • Los Angeles, California, United States, 90017
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
    • Lakewood, Colorado, United States, 80228
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  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20016
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  • Florida
    • Jacksonville, Florida, United States, 32224
      • Research Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
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  • Kentucky
    • Louisville, Kentucky, United States, 40202
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  • Maryland
    • Bethesda, Maryland, United States, 20817
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  • Massachusetts
    • Boston, Massachusetts, United States, 02114
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  • Michigan
    • Detroit, Michigan, United States, 48202
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  • Minnesota
    • Rochester, Minnesota, United States, 55905
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  • Missouri
    • St Louis, Missouri, United States, 63110
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  • New Jersey
    • Summit, New Jersey, United States, 07901
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  • New York
    • Westbury, New York, United States, 11590
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  • Ohio
    • Columbus, Ohio, United States, 43210
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  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
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  • Tennessee
    • Nashville, Tennessee, United States, 37232
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  • Texas
    • Austin, Texas, United States, 78731
      • Research Site
    • Dallas, Texas, United States, 75246
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
    • Houston, Texas, United States, 77090
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  • Virginia
    • Norfolk, Virginia, United States, 23502
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  • Washington
    • Seattle, Washington, United States, 98104
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  • Wisconsin
    • Madison, Wisconsin, United States, 53792-5666
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 105 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Patients must be ≥18 years of age

• Pathologically documented breast cancer that:

  1. is advanced or metastatic
  2. has a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested)
  3. has HER2-low or HER2 IHC >0 <1+ expression as determined by the central laboratory result established on a tissue sample taken in the metastatic setting
  4. was never previously HER2-positive
  5. is documented HR+ disease in the metastatic setting.
• No prior chemotherapy for advanced or metastatic breast cancer.
• Has adequate tumor samples for assessment of HER2 status

• Must have either:

  1. disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or
  2. disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the ≥2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting.
• Has protocol-defined adequate organ and bone marrow function

Key Exclusion Criteria:

• Ineligible for all options in the investigator's choice chemotherapy arm
• Lung-specific intercurrent clinically significant illnesses
• Uncontrolled or significant cardiovascular disease or infection
• Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by imaging at screening.
• Patients with spinal cord compression or clinically active central nervous system metastases
• Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trastuzumab deruxtecan; Trastuzumab deruxtecan (T-DXd; DS-8201a) arm	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan by intravenous infusion; Other Names: DS-8201a; T-DXd
Active Comparator: Standard of Care; Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm	Drug: Capecitabine; Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally.; Drug: Paclitaxel; Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion.; Drug: Nab-Paclitaxel; Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Low Population	PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by BICR was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 millimeter (mm) from nadir. Median PFS was calculated using Kaplan-Meier method and its confidence interval (CI) using Brookmeyer-Crowley method.	Response evaluations performed at screening, every 6 weeks (q6w) ± 1 week from randomization for 48 weeks, and then every 9 weeks (q9w) ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population	OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Median OS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.	From date of randomization until death due to any cause, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population	PFS per RECIST 1.1 assessed by BICR was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median PFS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.	Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Overall Survival (OS) in the Intent-to-Treat Population	OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Median OS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.	From date of randomization until death due to any cause, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Progression-Free Survival Assessed by Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population	PFS per RECIST 1.1 assessed by Investigator was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median PFS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.	Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Objective Response Rate (ORR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population	ORR per RECIST 1.1 assessed by BICR and Investigator was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR). CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.	Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Duration of Response (DOR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population	DOR per RECIST v1.1 was defined as the time from the date of first documented response until date of documented progression or death in the absence of PD. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median DOR was calculated using Kaplan-Meier method.	Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population	ORR per RECIST 1.1 assessed by BICR and Investigator was defined as the percentage of participants with at least 1 visit response of CR or PR. CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.	Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Duration of Response Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat Population	DOR per RECIST v1.1 was defined as the time from the date of first documented response until date of documented progression or death in the absence of PD. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median DOR was calculated using Kaplan-Meier method.	Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Time From Randomization to Second Progression or Death (PFS2) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population	PFS2 was defined as time from randomization to second progression (the earliest of the progression event subsequent to first subsequent therapy) or death; second progression was defined according to local standard clinical practice and might involve any of the following: objective radiological imaging, symptomatic progression, or death. Median PFS2 was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.	Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant administered a medicinal product and which did not necessarily had a causal relationship with this treatment. A serious adverse event (SAE) was an AE occurring during any study phase, that fulfilled 1 or more of following criteria: resulted in death, was immediately life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was congenital abnormality or birth defect, and was an important medical event that jeopardized participant or required medical treatment to prevent 1 of outcomes listed above. TEAE was any AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiation of the study drug until the 40-day (+7 days) safety follow-up visit.	From first dose of study drug (Day 1) up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a	Blood samples were collected at indicated time points to determine the concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a in serum.	Pre-dose on Day 1 of Cycles 1, 2, 4, 6 and 8; 15 minutes post-dose on Day 1 of Cycles 1, 2 and 4; and 5 hours post-dose on Day 1 of Cycle 1 (each cycle is 21 days)
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91	EORTC QLQ-C30 is a 30-item self-administered questionnaire grouped into 5 multi-item functional scales(physical,role,emotional,cognitive and social),3 multiitem symptom scales(fatigue,pain and nausea/vomiting),2-item global QoL scale,5 single items assessing additional symptoms reported by cancer participants(dyspnea,loss of appetite,insomnia,constipation and diarrhea). All but 2 questions have 4-point scales:1:not at all,2:a little,3:quite a bit,4:very much.2 questions concerning global health status and QoL have 7-point scales with responses ranging from 1:very poor to 7:excellent;higher score:better level of functioning/greater degree of symptoms.For each of 15 scales,final scores were averaged from scores of component items,transformed,range: 0 to 100;higher scores:better functioning,better health related (HR)QoL,or greater level of symptoms(higher scores:opposite interpretations for functioning/QoL and symptoms/problems).Baseline:last observed measurement prior to randomization.	Baseline (Day 1) and Week 91
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58	EORTC QLQ-BR45 is an updated version of the BR23. Self-administered instrument includes original 23-items yielding 5 multi-item scores (body image, sexual functioning, arm symptoms, breast symptoms, and systemic therapy side effects). Additional 22 items yield 4 additional multi-item scales (breast satisfaction, endocrine therapy symptoms, skin mucosis symptoms, and endocrine sexual symptoms). Single items assess sexual enjoyment, future perspective and being upset by hair loss. Items are scored on a 4-point verbal rating scale: 1: not at all, 2: a little, 3: quite a bit, and 4: very much; higher score: better level of functioning or greater degree of symptoms. Scores of these scales were averaged from scores of component items, transformed, and ranged from 0 to 100; higher scores for functioning scales or items indicate better functioning, whereas higher scores for symptom scales or items represent a higher level of symptoms. Baseline:last observed measurement prior to randomization.	Baseline (Day 1) and Week 58
Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score	Time to deterioration was defined as the time from randomization until the date of the first clinically meaningful deterioration that was confirmed at next available assessment, at least 14 days apart, regardless of whether the participant withdrew from study treatment or receives another anti-cancer therapy prior to deterioration.	From randomization until date of first symptom deterioration that is confirmed, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab Deruxtecan	Blood samples were collected at indicated timepoints to determine ADA. Treatment-induced ADA was defined as ADA positive post-baseline and not detected at baseline (negative or missing). Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following drug administration.	From Day 1 up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Time to First Subsequent Treatment or Death (TFST) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population	TFST was defined as time from randomization to the start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment or death due to any cause.	From Day 1 up to 64 months
Time to Second Subsequent Treatment or Death (TSST) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population	TSST was defined as time from randomization to the start date of the second subsequent anti-cancer therapy after discontinuation of randomized treatment or death due to any cause.	From Day 1 up to 64 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Daiichi Sankyo

Publications and helpful links

General Publications

• Tarantino P, Tolaney SM, Curigliano G. Trastuzumab deruxtecan (T-DXd) in HER2-low metastatic breast cancer treatment. Ann Oncol. 2023 Oct;34(10):949-950. doi: 10.1016/j.annonc.2023.07.003. Epub 2023 Jul 26. No abstract available.
• Bardia A, Hu X, Dent R, Yonemori K, Barrios CH, O'Shaughnessy JA, Wildiers H, Pierga JY, Zhang Q, Saura C, Biganzoli L, Sohn J, Im SA, Levy C, Jacot W, Begbie N, Ke J, Patel G, Curigliano G; DESTINY-Breast06 Trial Investigators. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. N Engl J Med. 2024 Dec 5;391(22):2110-2122. doi: 10.1056/NEJMoa2407086. Epub 2024 Sep 15.

Helpful Links

• Daiichi Sankyo Contact for Clinical Trial Information Phone: 908-992-6400
• AZ Breast Cancer Study Navigators
• D9670C00001_CSP_Redacted
• D9670C00001_CSR Synopsis_Redacted
• D9670C00001_Statistical Analysis Plan (SAP)

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2020
• Primary Completion (Actual): March 18, 2024
• Study Completion (Estimated): June 19, 2026

Study Registration Dates

• First Submitted: July 20, 2020
• First Submitted That Met QC Criteria: July 28, 2020
• First Posted (Actual): July 31, 2020

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer; HER2-Negative; HR positive; Anti-HER2-Antibody Drug Conjugate (ADC); HER2-Low; Trastuzumab Deruxtecan (T-DXd; DS-8201a); DESTINY-Breast06
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Paclitaxel; 130-nm albumin-bound paclitaxel; trastuzumab deruxtecan
• Other Study ID Numbers: D9670C00001; 2019-004493-26 (EudraCT Number); 2023-505554-18-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No