A Study of T-DXd in Participants With or Without Brain Metastasis Who Have Previously Treated Advanced or Metastatic HER2 Positive Breast Cancer

NCT04739761 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: D9673C000072024-510588-53-002020-005048-46
• Study Type: interventional
• Target: 506
• Locations: 18 countries
• Sites: 81

Brief Summary

This is open-label, multicenter, international study, assessing the efficacy and safety of Trastuzumab deruxtecan (T-DXd) in participants with or without brain metastasis (BMs), with previously-treated advanced/metastatic HER2-positive breast cancer whose disease has progressed on prior anti-HER2-based regimens and who received no more than 2 lines/regimens of therapy in the metastatic setting (excluding tucatinib).

Conditions

Breast Cancer

Keywords

Trastuzumab deruxtecan; Human epidermal growth factor receptor 2 Positive Breast Cancer; Brain Metastasis

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR) in Cohort 1 (Participants Without Brain Metastasis at Baseline)

  The ORR is defined as the percentage (%) of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by independent central review (ICR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

  From first dose (Day 1) to progression of disease (up to 2 years 7 months)

• Progression-free Survival (PFS) Rate at 12 Months in Cohort 2 (Participants With Brain Metastasis at Baseline)

  The PFS rate is the percentage of participants alive and free of disease progression at 12 months, estimated by the Kaplan-Meier method.

  At 12 months

Secondary Outcomes (25)

• Survival Rate at 12 Months

  At 12 Months

• Objective Response Rate in Cohort 2 (Participants With Brain Metastasis at Baseline)

  From first dose (Day 1) to progression of disease (up to 2 years 7 months)

• Duration of Response (DoR)

  From the date of first documented confirmed response until date of documented progression (up to 2 years 7 months)

• Time to Progression

  From first dose (Day 1) to progression of disease (up to 2 years 7 months)

• Duration of Treatment on Subsequent Lines of Therapy

  From the date of first dose of a subsequent therapy until date of last dose of therapy (up to 2 years 7 months)

Study Arms (1)

Trastuzumab Deruxtecan

EXPERIMENTAL

Participants with or without BM at baseline will receive intravenous (IV) T-DXd, 5.4 mg/kg, every 3 weeks (21-day cycle) until Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) defined radiological progression outside central nervous system, unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.

Drug: Trastuzumab Deruxtecan

Interventions

Trastuzumab Deruxtecan DRUG

Participants will receive T-DXd administered using an IV bag containing 5% (w/v) dextrose injection infusion solution.

Also known as: fam-trastuzumab deruxtecan-nxki

Trastuzumab Deruxtecan

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants should have pathologically documented breast cancer that is: unresectable/advanced or metastatic; confirmed HER2-positive status expression as determined according to American Society of Clinical Oncology/College of American Pathologists guidelines
• Participant must have either: no evidence of BM, or untreated BM on screening contrast brain magnetic resonance imaging/ computed tomography (MRI/CT) scan, not needing immediate local therapy or previously-treated stable or progressing BM
• Participants with BMs must be neurologically stable
• For participants requiring radiotherapy due to BMs, there should be an adequate washout period before day of first dosing:
• ≥ 7 days since stereotactic radiosurgery or gamma knife
• ≥ 21 days since whole brain radiotherapy
• Eastern Cooperative Oncology Group performance status 0-1
• Previous breast cancer treatment: radiologic or objective evidence of disease progression on or after HER2 targeted therapies and no more than 2 lines/regimens of therapy in the metastatic setting
• Participant with the following measurable: at least 1 lesion that can be accurately measured at baseline as ≥ 10 mm in the longest diameter with CT or MRI and is suitable for accurate repeated measurements; or following Non-measurable diseases: Non-measurable, bone-only disease that can be assessed by CT or MRI or X-Ray. Lytic or mixed lytic bone lesions that can be assessed by CT or MRI or X-ray in the absence of measurable disease as defined above is acceptable; Participants with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible; and Non-measurable CNS disease (Cohort 2 only)
• Adequate organ and bone marrow function within 14 days before the day of first dosing as defined in the protocol
• Left ventricular ejection fraction ≥ 50% within 28 days before enrollment
• Negative pregnancy test (serum) for women of childbearing potential

You may not qualify if:

• Known or suspected leptomeningeal disease
• Prior exposure to tucatinib treatment
• Refractory nausea and vomiting, chronic gastrointestinal disease, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of T-DXd
• 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
• Based on screening contrast brain MRI/CT scan, participants must not have any of the following: any untreated brain lesions \> 2.0 cm in size; ongoing use of systemic corticosteroids for control of symptoms of BMs; any brain lesion thought to require immediate local therapy; have poorly controlled (\> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to BMs not withstanding CNS-directed therapy
• Has spinal cord compression
• Known active hepatitis B or C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1. Participants with past or resolved hepatitis B virus infection are eligible, if negative for hepatitis B surface antigen and positive for anti-hepatitis B core antigen
• Participants positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
• Receipt of live, attenuated vaccine within 30 days prior to the first dose of T-DXd
• Participants with a medical history of myocardial infarction within 6 months before screening, symptomatic congestive heart failure (New York Heart Association Class II to IV)
• 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
• Lung-specific intercurrent clinically significant illnesses and any autoimmune, connective tissue or inflammatory disorders
• Prior exposure, without adequate treatment washout period before the day of first dosing, to chloroquine/hydroxychloroquine: \< 14 days
• Anticancer chemotherapy: immunotherapy (non-antibody-based therapy), retinoid therapy, hormonal therapy: \< 3 weeks

Sponsors & Collaborators

• AstraZeneca: lead
• Daiichi Sankyo: collaborator

Study Sites (81)

Research Site

Boston, Massachusetts, 02215, United States

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Durham, North Carolina, 27710, United States

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Adelaide, 5000, Australia

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Auchenflower, 4066, Australia

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Clayton, 3168, Australia

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Heidelberg, 3084, Australia

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St Leonards, 2065, Australia

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Subiaco, 6008, Australia

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Anderlecht, 1070, Belgium

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Bruges, 8000, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Vancouver, British Columbia, V5Z 1H7, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Copenhagen, 2100, Denmark

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Herlev, 2730, Denmark

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Odense C, 5000, Denmark

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Helsinki, 00290, Finland

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Tampere, FI-33521, Finland

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Turku, 20520, Finland

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Berlin, 13125, Germany

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Dresden, 1307, Germany

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Erlangen, 91054, Germany

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Essen, 45136, Germany

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Frankfurt, 60389, Germany

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Hamburg, 20246, Germany

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Hanover, 30625, Germany

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Kiel, 24105, Germany

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Mannheim, 68167, Germany

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München, 80336, Germany

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München, 80637, Germany

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Münster, 48149, Germany

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Tübingen, 72076, Germany

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Cork, T12 DV56, Ireland

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Dublin, 7, Ireland

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Dublin, D04 Y8V0, Ireland

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Ancona, 60122, Italy

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Bergamo, 24127, Italy

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Catania, 95126, Italy

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Milan, 20132, 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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Isehara, 259-1193, Japan

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Kawasaki-shi, 216-8511, Japan

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Sapporo, 003-0804, Japan

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Shinagawa-ku, 142-8666, Japan

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Yokohama, 241-8515, Japan

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Maastricht, 6229 HX, Netherlands

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The Hague, 2545 AA, Netherlands

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Bergen, 5009, Norway

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Oslo, 450, Norway

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Oslo, N-0379, Norway

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Gdansk, 80-214, Poland

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Krakow, 31-501, Poland

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Opole, 45-060, Poland

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Warsaw, 02-781, Poland

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Warsaw, 04-141, Poland

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Lisbon, 1400-048, Portugal

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Lisbon, 1649-035, Portugal

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Porto, 4099-001, Portugal

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Barcelona, 08036, Spain

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Barcelona, 8035, Spain

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Bilbao (Vizcaya), 48013, Spain

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Granada, 18014, Spain

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Madrid, 28005, Spain

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Madrid, 28034, Spain

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Madrid, 28041, Spain

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Salamanca, 37007, Spain

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Santander, 39008, Spain

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Santiago de Compostela-Coruña, 15706, Spain

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Seville, 41013, Spain

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Valencia, 46009, Spain

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Gothenburg, 413 45, Sweden

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Lund, 221 85, Sweden

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Uppsala, 751 85, Sweden

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Basel, 4031, Switzerland

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Bellinzona, CH-6500, Switzerland

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Lausanne, 1011, Switzerland

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Lucerne, 6000, Switzerland

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Edinburgh, EH4 2XR, United Kingdom

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Related Publications (1)

• Harbeck N, Ciruelos E, Jerusalem G, Muller V, Niikura N, Viale G, Bartsch R, Kurzeder C, Higgins MJ, Connolly RM, Baron-Hay S, Gion M, Guarneri V, Bianchini G, Wildiers H, Escriva-de-Romani S, Prahladan M, Bridge H, Kuptsova-Clarkson N, Scotto N, Verma S, Lin NU; DESTINY-Breast12 study group. Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial. Nat Med. 2024 Dec;30(12):3717-3727. doi: 10.1038/s41591-024-03261-7. Epub 2024 Sep 13.

  PMID: 39271844 DERIVED

Related Links

• Redacted Statistical Analysis Plan
• Redacted CSP
• Redacted CSR synopsis

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Nadia Harbeck, MD, PhD

  Head, Breast Center, Ludwig-Maximilians-University of Munich Department of Obstetrics and Gynecology Marchioninistr. 15, 81377 Munich, Germany

  PRINCIPAL INVESTIGATOR

• Nancy U. Lin, MD

  Associate Chief, Division of Breast Oncology, Susan F. Smith Center for Women's Cancers Director, Metastatic Breast Cancer Program, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2021
• First Posted: February 5, 2021
• Study Start: June 22, 2021
• Primary Completion: February 8, 2024
• Study Completion (Estimated): May 26, 2027
• Last Updated: May 12, 2026
• Results First Posted: May 16, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• 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 refer 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.

Locations

GB (1); NL (2); NO (3); PT (3); DE (13); US (2); IE (3); BE (4); CA (2); JP (5); PL (5); DK (3); ES (12); CH (4); IT (7); FI (3); AU (6); SE (3)