NCT05104866

Brief Summary

The study will evaluate the safety and efficacy of datopotamab deruxtecan (also known as Dato-DXd, DS-1062a), when compared with Investigator's choice of standard of care single-agent chemotherapy (eribulin, capecitabine, vinorelbine, or gemcitabine) in participants with inoperable or metastatic HR-positive, HER2- negative breast cancer who have been treated with one or two prior lines of systemic chemotherapy.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
732

participants targeted

Target at P50-P75 for phase_3 breast-cancer

Timeline
3mo left

Started Oct 2021

Geographic Reach
20 countries

167 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress95%
Oct 2021Jul 2026

First Submitted

Initial submission to the registry

October 4, 2021

Completed
14 days until next milestone

Study Start

First participant enrolled

October 18, 2021

Completed
16 days until next milestone

First Posted

Study publicly available on registry

November 3, 2021

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 24, 2024

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

February 4, 2026

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2026

Expected
Last Updated

May 5, 2026

Status Verified

May 1, 2026

Enrollment Period

2.8 years

First QC Date

October 4, 2021

Results QC Date

July 23, 2025

Last Update Submit

May 4, 2026

Conditions

Keywords

Breast CancerHR positiveHormone Receptor positiveER positivePR positiveHER2 negativeInoperableMetastaticDatopotamab DeruxtecanDato-DXdDS1062DS1062aCapecitabineEribulinGemcitabineVinorelbineTROP2Antibody Drug ConjugateADC

Outcome Measures

Primary Outcomes (2)

  • Progression-Free Survival

    PFS is defined as time from randomization until progression per RECIST 1.1, as assessed by BICR, or death due to any cause. The analysis will include all randomized participants as randomized regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy, or clinically progresses prior to RECIST 1.1.

    On-study tumor assessments occur every 6 weeks then every 9 weeks until disease progression, death or withdrawal of consent assessed up to data cut-off (17Jul2023) to a maximum of approximately 21 months

  • Overall Survival

    OS is defined as time from randomization until the date of death due to any cause. The comparison will include all randomized participants as randomized, regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy. The measure of interest is the hazard ratio of OS.

    From date of randomization until death due to any cause. Assessed up to data cut-off (24Jul2024) to a maximum of approximately 33 months.

Secondary Outcomes (11)

  • Objective Response Rate (ORR)

    From date of randomization until event. Assessed up to data cut-off (17Jul2023) to a maximum of approximately 21 months for BICR assessment and assessed up to data cut-off (24Jul2024) to a maximum of approximately 33 months for investigator assessment.

  • Duration of Response (DoR) as Assessed by BICR Assessment

    From date of first response until progression or death. Tumor assessments occur every 6 weeks then every 9 weeks until disease progression, death or withdrawal of consent. Assessed up to data cut-off (17Jul2023) to a maximum of approximately 21 months.

  • Duration of Response (DoR) as Assessed by Investigator Assessment

    From date of first response until progression or death. Tumor assessments occur every 6 weeks then every 9 weeks until disease progression, death or withdrawal of consent. Assessed up to data cut-off (24Jul2024) to a maximum of approximately 33 months

  • Progression-Free Survival by Investigator Assessment

    On-study tumor assessments occur every 6 weeks then every 9 weeks until disease progression, death or withdrawal of consent assessed up to data cut-off (24Jul2024) to a maximum of approximately 33 months

  • Disease Control Rate (DCR)

    Assessed up to data cut-off (17Jul2023) to a maximum of 21 months for BICR assessment and assessed up to data cut-off (24Jul2024) to a maximum of 33 months for investigator assessment.

  • +6 more secondary outcomes

Study Arms (2)

Dato-DXd

EXPERIMENTAL

Arm 1: Dato-DXd

Drug: Dato-DXd

Investigators Choice of Chemotherapy (ICC)

ACTIVE COMPARATOR

Arm 2: ICC Capecitabine Gemcitabine Eribulin mesylate Vinorelbine

Drug: CapecitabineDrug: GemcitabineDrug: EribulinDrug: Vinorelbine

Interventions

Experimental drug. Provided in 100mg vials. IV infusion.

Also known as: Datopotamab deruxtecan (Dato-DXd, DS-1062a)
Dato-DXd

Tablet. Oral route of administration. Active comparator

Investigators Choice of Chemotherapy (ICC)

IV Infusion. Active comparator

Investigators Choice of Chemotherapy (ICC)

IV Infusion. Active comparator

Also known as: Eribulin Mesylate
Investigators Choice of Chemotherapy (ICC)

IV Infusion. Active comparator

Investigators Choice of Chemotherapy (ICC)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age • Participant must be ≥ 18 years at the time of screening.
  • Type of Participant and Disease Characteristics
  • Inoperable or metastatic HR+, HER2-negative breast cancer
  • Progressed on and not suitable for endocrine therapy per investigator assessment and treated with 1 to 2 lines of prior chemotherapy in the inoperable/metastatic setting. Participant must have documented progression on their most recent line of chemotherapy.
  • Eligible for one of the chemotherapy options listed as ICC (eribulin, capecitabine, vinorelbine, gemcitabine), per investigator assessment.
  • ECOG PS of 0 or 1, with no deterioration over the previous 2 weeks prior to day of first dosing.
  • At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1. Note: Participants with bone-only metastases are not permitted.
  • Participants with a history of previously treated neoplastic spinal cord compression, or clinically inactive brain metastases, 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 weeks must have elapsed between the end of radiotherapy and study enrolment.
  • Adequate organ and bone marrow function within 7 days before day of first dosing as follows:
  • Hemoglobin: ≥ 9.0 g/L.
  • Absolute neutrophil count: 1500/mm3.
  • Platelet count: 100000/mm3. • Total bilirubin: ≤ 1.5 × ULN if no liver metastases; or ≤ 3 × ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.
  • ALT and AST: ≤ 3 × ULN for AST/ALT; however, if elevation is due to liver metastases, ≤ 5.0 × ULN is allowed.
  • Calculated creatinine clearance: ≥ 30 mL/min as calculated using the Cockcroft-Gault equation (using actual body weight).
  • LVEF ≥ 50% by either an echocardiogram or MUGA within 28 days of first dosing.
  • +18 more criteria

You may not qualify if:

  • Medical Conditions
  • Any evidence of diseases which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
  • History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy, adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated.
  • Persistent toxicities caused by previous anticancer therapy (excluding alopecia), not yet improved to CTCAE Version 5.0 Grade ≤ 1 or baseline. Note: participants may be enrolled with some chronic, stable Grade 2 toxicities (defined as no worsening to \> Grade 2 for at least 3 months prior to first dosing and managed with SoC treatment) which the investigator deems related to previous anticancer therapy.
  • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections.
  • Known active or uncontrolled hepatitis B or C infection; or positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (HBsAg, anti-HBs, anti-HBc, or HBV DNA) or hepatitis C (HCV antibody or HCV RNA) infection at screening.
  • Known HIV infection that is not well controlled.
  • Uncontrolled or significant cardiac disease, including myocardial infarction or uncontrolled/unstable angina within 6 months prior to C1D1, CHF (New York Heart Association Class II to IV), uncontrolled or significant cardiac arrhythmia, or uncontrolled hypertension (resting systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 110 mmHg).
  • Investigator judgment of 1 or more of the following:
  • Mean resting corrected QTcF interval \> 470 ms , obtained from triplicate ECGs performed at screening.
  • History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause Torsades de Pointes.
  • Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
  • History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
  • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement, or prior pneumonectomy.
  • Leptomeningeal carcinomatosis.
  • +19 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (167)

Research Site

Duarte, California, 91010, United States

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Los Angeles, California, 90095, United States

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Palo Alto, California, 94305-5826, United States

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San Francisco, California, 94143, United States

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Jacksonville, Florida, 32207, United States

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Atlanta, Georgia, 30322, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02215, United States

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Grand Rapids, Michigan, 49503, United States

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New York, New York, 10065, United States

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Cleveland, Ohio, 44119, United States

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Portland, Oregon, 97239, United States

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Nashville, Tennessee, 37203, United States

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Richmond, Virginia, 23219, United States

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CABA, 1414, Argentina

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Ciudad de Buenos Aires, C1280AEB, Argentina

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La Plata, 1900, Argentina

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Mar del Plata, 7600, Argentina

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Rosario, 2000, Argentina

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Rosario, 2123, Argentina

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Anderlecht, 1070, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Itajaí, 88301-220, Brazil

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Jaú, 17210-070, Brazil

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Porto Alegre, 90035903, Brazil

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Ribeirão Preto, 14051-140, Brazil

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Rio de Janeiro, 20560-120, Brazil

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São Paulo, 01236-030, Brazil

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São Paulo, 01246-000, Brazil

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São Paulo, 01509-900, Brazil

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São Paulo, 1323001, Brazil

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North York, Ontario, M2K 1E1, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Québec, Quebec, G1S 4L8, Canada

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Baoding, 071000, China

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Beijing, 100044, China

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Beijing, 100071, China

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Beijing, 100210, China

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Bengbu, 233004, China

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Changchun, 130021, China

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Changsha, 410013, China

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Chengdu, 610000, China

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Guangzhou, 510060, China

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Hangzhou, 310003, China

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Hangzhou, 310020, China

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Hangzhou, 310022, China

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Harbin, 150049, China

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Jinan, 250001, China

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Jinan, 250117, China

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Linyi, 276000, China

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Nanchang, 330006, China

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Nanchang, 330009, China

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Shanghai, 200000, China

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Tianjin, 300060, China

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Xiamen, 361003, China

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Bezannes, 51430, France

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Bordeaux, 33030, France

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Lille, 59000, France

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Lyon, 69008, France

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Montpellier, 34070, France

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Plérin, 22190, France

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Toulouse, 31059, France

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Villejuif, 94800, France

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Heidelberg, 69120, Germany

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Homburg, 66421, Germany

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Leipzig, 4103, Germany

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München, 80637, Germany

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Ravensburg, 88212, Germany

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Budapest, 1062, Hungary

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Budapest, 1122, Hungary

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Szekszárd, 7100, Hungary

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Szolnok, 5000, Hungary

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Gurgaon, 122001, India

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Howrah, 711103, India

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Hyderabad, 500084, India

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Jaipur, 302022, India

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Kolkata, 700160, India

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Nashik, 422009, India

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Surat, 395002, India

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Visakhapatnam, 530017, India

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Bologna, 40138, Italy

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Candiolo, 10060, Italy

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Florence, 50139, Italy

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Meldola, 47014, Italy

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Milan, 20132, Italy

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Milan, 20141, Italy

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Naples, 80131, Italy

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Padova, 35128, Italy

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Prato, 59100, Italy

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Roma, 00168, Italy

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Chūōku, 104-0045, Japan

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Fukuoka, 811-1395, Japan

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Fukushima, 960-1295, Japan

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Hiroshima, 730-8518, Japan

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Isehara-shi, 259-1193, Japan

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Kagoshima, 892-0833, Japan

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Kashiwa, 227-8577, Japan

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Kitaadachi-gun, 362-0806, Japan

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Kōtoku, 135-8550, Japan

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Kyoto, 606-8507, Japan

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Matsuyama, 791-0280, Japan

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Nagoya, 464-8681, Japan

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Nishinomiya-shi, 663-8501, Japan

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Osaka, 541-8567, Japan

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Osakasayama-shi, 589-8511, Japan

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Sapporo, 003-0804, Japan

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Shinagawa-ku, 142-8666, Japan

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Shinjuku-ku, 162-8655, Japan

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Yokohama, 241-8515, Japan

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Amsterdam, 1081 HV, Netherlands

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Rotterdam, 3083 AN, Netherlands

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Venlo, 5912 BL, Netherlands

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Bialystok, 15-027, Poland

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Gdansk, 80-952, Poland

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Gdynia, 81-519, Poland

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Konin, 62-500, Poland

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Koszalin, 75-581, Poland

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Lodz, 90-302, Poland

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Tomaszów Mazowiecki, 97-200, Poland

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Warsaw, 02-781, Poland

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Moscow, 115478, Russia

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Moscow, 143423, Russia

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George, 6529, South Africa

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Johannesburg, 2013, South Africa

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Johannesburg, 2196, South Africa

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Port Elizabeth, 6045, South Africa

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Pretoria, 0081, South Africa

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Goyang-si, 10408, South Korea

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Seoul, 02841, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Seoul, 6273, South Korea

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A Coruña, 15006, Spain

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Barcelona, 08028, Spain

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Barcelona, 8036, Spain

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Bilbao (Vizcaya), 48013, Spain

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Huelva, 21005, Spain

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L'Hospitalet de Llobregat, 08908, Spain

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Madrid, 28034, Spain

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Madrid, 28040, Spain

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Málaga, 29010, Spain

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Seville, 41013, Spain

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Valencia, 46010, Spain

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Kaohsiung City, 82445, Taiwan

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Kaohsiung City, 833, Taiwan

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Taichung, 40447, Taiwan

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Tainan, 70403, Taiwan

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Taipei, 10050, Taiwan

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Taipei, 10449, Taiwan

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Taipei, 11217, Taiwan

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Taoyuan, 333, Taiwan

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Blackpool, FY3 8NR, United Kingdom

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Bristol, BS2 8ED, United Kingdom

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Cardiff, CF14 2TL, United Kingdom

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Colchester, CO4 5JL, United Kingdom

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Edinburgh, EH4 2XU, United Kingdom

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London, EC1A 7BE, United Kingdom

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London, SW3 6JJ, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Sutton, SM2 5PT, United Kingdom

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Truro, TR1 3LJ, United Kingdom

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Related Publications (2)

  • Bardia A, Jhaveri K, Im SA, Pernas S, De Laurentiis M, Wang S, Martinez Janez N, Borges G, Cescon DW, Hattori M, Lu YS, Hamilton E, Zhang Q, Tsurutani J, Kalinsky K, Rubini Liedke PE, Xu L, Fairhurst RM, Khan S, Denduluri N, Rugo HS, Xu B, Pistilli B; TROPION-Breast01 Investigators. Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Primary Results From TROPION-Breast01. J Clin Oncol. 2025 Jan 20;43(3):285-296. doi: 10.1200/JCO.24.00920. Epub 2024 Sep 12.

  • Bardia A, Jhaveri K, Kalinsky K, Pernas S, Tsurutani J, Xu B, Hamilton E, Im SA, Nowecki Z, Sohn J, Laurentiis M, Janez NM, Adamo B, Lee KS, Jung KH, Rubovszky G, Tseng LM, Lu YS, Yuan Y, Maxwell MJ, Haddad V, Khan SS, Rugo HS, Pistilli B. TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer. Future Oncol. 2024 Mar;20(8):423-436. doi: 10.2217/fon-2023-0188. Epub 2023 Jun 30.

Related Links

MeSH Terms

Conditions

Breast NeoplasmsNeoplasm Metastasis

Interventions

CapecitabineGemcitabineeribulinVinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFluorouracilUracilPyrimidinonesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizines

Results Point of Contact

Title
Global Clinical Lead
Organization
AstraZeneca Clinical Study Information Center

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Parallel
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 4, 2021

First Posted

November 3, 2021

Study Start

October 18, 2021

Primary Completion

July 24, 2024

Study Completion (Estimated)

July 31, 2026

Last Updated

May 5, 2026

Results First Posted

February 4, 2026

Record last verified: 2026-05

Data Sharing

IPD Sharing
Will share

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

Shared Documents
STUDY PROTOCOL, SAP
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.
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.
More information

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