A Phase III, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy (Paclitaxel, Nab-paclitaxel or Gemcitabine + Carboplatin) in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION-Breast05)

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Investigational drug late phase More information Active drug More information Moderate burden on patient More information

Trial Details

Sponsor: AstraZeneca (industry)

Phase: 3

Start date: Nov. 23, 2023

Planned enrollment: 625

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Trial ID: NCT06103864
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More trial details at ClinicalTrials.gov More info

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Goal: To determine whether datopotamab deruxtecan (Dato-DXd) with or without durvalumab improves progression-free survival compared to investigator's choice of chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) in combination with pembrolizumab for patients with PD-L1 positive, locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC).

Patients: Patients enrolled have histologically or cytologically confirmed, locally recurrent inoperable or metastatic TNBC that is PD-L1 positive (CPS ≥ 10), with no prior chemotherapy or systemic therapy for metastatic or locally recurrent inoperable breast cancer. Eligible patients must have ECOG PS 0-1 and measurable disease per RECIST 1.1. Both male and female patients are eligible, with requirements for adequate organ function and tissue availability.

Design: This is a randomized, open-label, multicenter, international phase III study with three arms and stratification by geography, disease-free interval, and prior PD-1/PD-L1 exposure. Participants are randomized to one of three arms: Dato-DXd plus durvalumab, Dato-DXd monotherapy, or investigator’s choice chemotherapy with pembrolizumab.

Treatments: The investigational treatment is datopotamab deruxtecan (Dato-DXd), an antibody-drug conjugate targeting TROP2, linked to a topoisomerase I inhibitor payload. Dato-DXd binds TROP2 on tumor cells, is internalized, and delivers a cytotoxic agent that induces DNA damage; the membrane-permeable payload enables bystander killing. In prior phase III studies in lung and breast cancer, Dato-DXd showed improved progression-free survival (e.g., TROPION-Lung01 median PFS 4.4 vs 3.7 months vs docetaxel, HR 0.75), and a generally manageable safety profile, with stomatitis, nausea, and interstitial lung disease/pneumonitis among notable adverse events. Durvalumab, a PD-L1 inhibitor, is combined in one investigational arm. The comparator arm employs investigator’s choice of paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin, each in combination with pembrolizumab, an approved PD-1 inhibitor.

Outcomes: The primary endpoint is progression-free survival (PFS) by blinded independent central review per RECIST 1.1. Key secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response, investigator-assessed PFS, clinical benefit rate at 24 weeks, various patient-reported outcomes (symptom and quality of life deterioration), time to first and second subsequent therapy, PFS2, pharmacokinetics and immunogenicity of Dato-DXd and its combination with durvalumab, and safety/tolerability measures.

Burden on patient: The patient burden is moderate and typical of international phase III registrational trials in metastatic breast cancer. Patients must provide tumor tissue for biomarker testing and undergo regular radiology assessments per RECIST, which are standard. Arm-specific procedures include intravenous administration of Dato-DXd and/or durvalumab under protocol-defined schedules, similar to chemotherapy plus pembrolizumab regimens. There may be additional pharmacokinetic and immunogenicity blood draws in the experimental arms, but otherwise, procedures align closely with standard of care; no research biopsies are described. Patient-reported outcome assessments are included but are non-invasive. Visits and imaging requirements reflect standard oncology practice for advanced breast cancer trials.

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Leipzig, 04103, Germany

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Georgsmarienhütte, 49124, Germany

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Essen, 45136, Germany

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Heilbronn, 74078, Germany

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Nagpur, 440001, India

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Calicut, 673601, India

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Chennai, 600031, India

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Kochi, 682027, India

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Kolkata, 700160, India

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Marg Jaipur, 302004, India

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Mohali, 160055, India

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Mysuru, 570017, India

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Nashik, 422009, India

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New Delhi, 110075, India

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New Delhi, 11029, India

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Pondicherry, 605006, India

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Surat, 395002, India

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Thiruvananthapuram, 695011, India

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Vadodara, 391760, India

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Vishakapatnam, 530053, India

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Rozzano, 20089, Italy

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Roma, 00168, Italy

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Bergamo, 24127, Italy

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Reggio Emilia, 42123, Italy

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Padova, 35128, Italy

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Modena, 41124, Italy

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Milan, 20141, Italy

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Empoli, 50053, Italy

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Sendai-shi, 980-8574, Japan

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Nishinomiya-shi, 663-8501, Japan

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Nagoya-shi, 467-8602, Japan

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Matsuyama-shi, 791-0280, Japan

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Kumamoto-shi, 860-8556, Japan

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Koto-ku, 135-8550, Japan

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Kitaadachi-gun, 362-0806, Japan

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Kashiwa, 277-8577, Japan

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Hidaka-shi, 350-1298, Japan

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Osaka-shi, 541-8567, Japan

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Akashi-shi, 673-8558, Japan

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Busan, 49241, Korea, Republic of

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Singapore, 308433, Singapore

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Singapore, 329563, Singapore

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Singapore, 119228, Singapore

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Paarl, 7646, South Africa

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Cape Town, 7570, South Africa

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Johannesburg, 2013, South Africa

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Johannesburg, 2193, South Africa

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Madrid, 28007, Spain

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Barcelona, 08028, Spain

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Barcelona, 8035, Spain

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Granada, 18016, Spain

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Hospitalet deLlobregat, 08907, Spain

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Madrid, 28034, Spain

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Pamplona, 31008, Spain

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Santander, 39008, Spain

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Taipei, 11259, Taiwan

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Taipei, 10449, Taiwan

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Taipei, 100, Taiwan

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Tainan, 704, Taiwan

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Taichung, 40447, Taiwan

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Kaohsiung, 80756, Taiwan

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Hsinchu, 300, Taiwan

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Taoyuan, 333, Taiwan

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Dusit, 10300, Thailand

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Chiang Mai, 50200, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10330, Thailand

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Bangkok, 10210, Thailand

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Songkhla, 90110, Thailand

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Khon Kaen, 40002, Thailand

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Samsun, 55200, Turkey

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Izmir, 35575, Turkey

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Besevler Ankara, Turkey

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Ankara, 6200, Turkey

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Ankara, 06520, Turkey

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Küçükçekmece, 34295, Turkey

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Chelsea, SW3 6JJ, United Kingdom

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London, SW17 0QT, United Kingdom

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London, EC1A 7BE, United Kingdom

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Liverpool, L7 8YA, United Kingdom

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Leicester, Le5 4PW, United Kingdom

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Status: Recruiting

Research Site

Cardiff, CF14 2TL, United Kingdom

No email / No phone

Status: Recruiting

Research Site

Taunton, TA1 5DA, United Kingdom

No email / No phone

Status: Recruiting

Research Site

Sutton, SM2 5PT, United Kingdom

No email / No phone

Status: Recruiting

Research Site

Surrey, GU2 7XX, United Kingdom

No email / No phone

Status: SUSPENDED

Research Site

Oxford, OX3 7LE, United Kingdom

No email / No phone

Status: Recruiting

Research Site

Daphne, Alabama, 36526, United States

No email / No phone

Status: Recruiting

Research Site

Springdale, Arkansas, 72762, United States

No email / No phone

Status: Recruiting

Research Site

Glendale, California, 91204, United States

No email / No phone

Status: Recruiting

Research Site

Duarte, California, 91010, United States

No email / No phone

Status: Withdrawn

Research Site

Sacramento, California, 95817, United States

No email / No phone

Status: Recruiting

Research Site

Santa Rosa, California, 95403, United States

No email / No phone

Status: Recruiting

Research Site

Aurora, Colorado, 80012, United States

No email / No phone

Status: Recruiting

Research Site

New Haven, Connecticut, 06510, United States

No email / No phone

Status: Recruiting

Research Site

Miami, Florida, 33176, United States

No email / No phone

Status: Recruiting

Research Site

Plantation, Florida, 33324, United States

No email / No phone

Status: Recruiting

Research Site

Jacksonville, Florida, 32256, United States

No email / No phone

Status: Recruiting

Research Site

Palm Bay, Florida, 32909, United States

No email / No phone

Status: Withdrawn

Research Site

Atlanta, Georgia, 30318, United States

No email / No phone

Status: SUSPENDED

Research Site

Honolulu, Hawaii, 96819, United States

No email / No phone

Status: Recruiting

Research Site

Chicago, Illinois, 60637, United States

No email / No phone

Status: Recruiting

Research Site

Naperville, Illinois, 60540, United States

No email / No phone

Status: Recruiting

Research Site

Elmhurst, Illinois, 60126, United States

No email / No phone

Status: Recruiting

Research Site

Decatur, Illinois, 62526, United States

No email / No phone

Status: Withdrawn

Research Site

New Albany, Indiana, 47150, United States

No email / No phone

Status: Recruiting

Research Site

Des Moines, Iowa, 50309, United States

No email / No phone

Status: Recruiting

Research Site

Louisville, Kentucky, 40202, United States

No email / No phone

Status: Recruiting

Research Site

Lexington, Kentucky, 40503, United States

No email / No phone

Status: Recruiting

Research Site

Louisville, Kentucky, 40202, United States

No email / No phone

Status: Withdrawn

Research Site

Louisville, Kentucky, 40207, United States

No email / No phone

Status: Recruiting

Research Site

Baton Rouge, Louisiana, 70809, United States

No email / No phone

Status: Recruiting

Research Site

Baton Rouge, Louisiana, 70808, United States

No email / No phone

Status: Recruiting

Research Site

Baltimore, Maryland, 21215, United States

No email / No phone

Status: Recruiting

Research Site

Columbia, Maryland, 21044, United States

No email / No phone

Status: Recruiting

Research Site

Boston, Massachusetts, 02111, United States

No email / No phone

Status: Withdrawn

Research Site

Worcester, Massachusetts, 01655, United States

No email / No phone

Status: Withdrawn

Research Site

Grand Rapids, Michigan, 49503, United States

No email / No phone

Status: Recruiting

Research Site

Detroit, Michigan, 48201, United States

No email / No phone

Status: Recruiting

Research Site

Saint Paul, Minnesota, 55109, United States

No email / No phone

Status: Recruiting

Research Site

Hattiesburg, Mississippi, 39401, United States

No email / No phone

Status: Withdrawn

Research Site

Saint Louis, Missouri, 63129, United States

No email / No phone

Status: Recruiting

Research Site

Albuquerque, New Mexico, 87109, United States

No email / No phone

Status: Recruiting

Research Site

Albany, New York, 12206, United States

No email / No phone

Status: Recruiting

Research Site

New York, New York, 10065, United States

No email / No phone

Status: Recruiting

Research Site

Stony Brook, New York, 11794-7263, United States

No email / No phone

Status: Recruiting

Research Site

Cincinnati, Ohio, 45219, United States

No email / No phone

Status: Recruiting

Research Site

Cleveland, Ohio, 44195, United States

No email / No phone

Status: Recruiting

Research Site

Cincinnati, Ohio, 45245, United States

No email / No phone

Status: Recruiting

Research Site

York, Pennsylvania, 17403, United States

No email / No phone

Status: Withdrawn

Research Site

Providence, Rhode Island, 02903, United States

No email / No phone

Status: Recruiting

Research Site

Nashville, Tennessee, 37203, United States

No email / No phone

Status: Recruiting

Research Site

Chattanooga, Tennessee, 37404, United States

No email / No phone

Status: Recruiting

Research Site

El Paso, Texas, 79902, United States

No email / No phone

Status: Recruiting

Research Site

Flower Mound, Texas, 75028, United States

No email / No phone

Status: Recruiting

Research Site

Fort Worth, Texas, 76104, United States

No email / No phone

Status: Recruiting

Research Site

Houston, Texas, 77054, United States

No email / No phone

Status: Withdrawn

Research Site

Houston, Texas, 77098, United States

No email / No phone

Status: Withdrawn

Research Site

Houston, Texas, 77090, United States

No email / No phone

Status: Recruiting

Research Site

Kingwood, Texas, 77339, United States

No email / No phone

Status: Withdrawn

Research Site

McKinney, Texas, 75071, United States

No email / No phone

Status: Withdrawn

Research Site

Sugar Land, Texas, 77479, United States

No email / No phone

Status: Recruiting

Research Site

Dallas, Texas, 75230, United States

No email / No phone

Status: Withdrawn

Research Site

Dallas, Texas, 75246, United States

No email / No phone

Status: Recruiting

Research Site

Dallas, Texas, 75246, United States

No email / No phone

Status: Withdrawn

Research Site

Norfolk, Virginia, 23502, United States

No email / No phone

Status: Recruiting

Research Site

Fairfax, Virginia, 22031, United States

No email / No phone

Status: Not yet recruiting

Research Site

Charlottesville, Virginia, 22903, United States

No email / No phone

Status: Recruiting

Research Site

Roanoke, Virginia, 24014, United States

No email / No phone

Status: Recruiting

Research Site

Midlothian, Virginia, 23114, United States

No email / No phone

Status: Recruiting

Research Site

Tacoma, Washington, 98405, United States

No email / No phone

Status: Recruiting

Research Site

Madison, Wisconsin, 53792, United States

No email / No phone

Status: Recruiting

Research Site

Ho Chi Minh City, 700000, Vietnam

No email / No phone

Status: Recruiting

Research Site

Vinh, 460000, Vietnam

No email / No phone

Status: Recruiting

Research Site

Hanoi, 100000, Vietnam

No email / No phone

Status: Recruiting

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