Back to Trials
NCT06103864PHASE3Recruiting

A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION-Breast05)

AstraZeneca

Start Date

11/23/2023

Completion Date

9/30/2030

Summary

This is a Phase III, randomised, open-label, 3-arm, multicentre, international study assessing the efficacy and safety of Dato-DXd with or without durvalumab compared with investigator's choice chemotherapy in combination with pembrolizumab in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.

Detailed Description

The primary objective of the study is to demonstrate superiority of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of PFS as assessed by BICR in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC. The study will be stratified based on geographic location (US/Canada/Europe vs. Dato-DXd monotherapy enrolling countries vs. rest of world), disease-free interval (DFI) history (de novo vs. prior DFI 6 to 12 months vs. prior DFI \> 12 months), and prior PD-1/PD-L1 treatment for early stage TNBC (yes vs. no). This study aims to see if Dato-DXd with durvalumab allows patients to live longer without their breast cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy and pembrolizumab. This study is also looking to see how the treatment and the breast cancer affects patients' quality of life.

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria * Histologically or cytologically documented locally recurrent inoperable, which cannot be treated with curative intent, or metastatic TNBC, as defined by the ASCO-CAP guidelines. * ECOG PS 0 or 1. * Participants are expected to provide an FFPE tumour sample collected from a locally recurrent inoperable or metastatic tumour. Alternatively, an archival FFPE tumour sample can be submitted; it must have been collected ≤ 3 years prior to the participant signing informed consent (screening start). * PD-L1 positive TNBC based on results from an appropriately validated investigational PD-L1 (22C3) assay (CPS ≥ 10) from a sponsor designated central laboratory. * No prior chemotherapy or other systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer. \- Patients with recurrent disease will be eligible if they have completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months have elapsed between completion of treatment with curative intent and the first documented recurrence. * Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin). * Measurable disease as per RECIST 1.1. * Adequate bone marrow reserve and organ function. * Male and female participants of childbearing potential must agree to use protocol-specified method(s) of contraception. Key Exclusion Criteria * As judged by investigator, any evidence of diseases (such as severe or uncontrolled medical conditions including systemic diseases, uncontrolled hypertension, serious gastrointestinal conditions associated with diarrhoea, chronic diverticulitis or previous complicated diverticulitis, history of allogeneic organ transplant, and active bleeding diseases, ongoing and active infection, significant cardiac conditions, substance abuse, psychiatric illness/social situation or psychological conditions) 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 2 years before Cycle 1 Day 1 and of low potential risk for recurrence. * Participants with a history of previously treated neoplastic spinal cord compression or treated, clinically inactive brain metastases that are no longer symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be included in the study if they have recovered from acute toxic effects of radiotherapy. \- Participants with treated clinically inactive brain metastases that are no longer symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be included in the study if they have recovered from acute toxic effects of radiotherapy. * Uncontrolled infection requiring IV antibiotics, antivirals or antifungals. * Active or uncontrolled hepatitis B or C virus infection. * Known HIV infection that is not well controlled. * Uncontrolled or significant cardiac disease. * History of non-infectious ILD/pneumonitis (including radiation pneumonitis) that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. * Clinically severe pulmonary function compromise. * Clinically significant corneal disease. * Active or prior documented autoimmune or inflammatory disorders. * Prior exposure to any treatment including ADC containing a chemotherapeutic agent targeting topoisomerase I and TROP2-targeted therapy. * Any concurrent anti-cancer treatment. * Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors or Dato-DXd. * Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.

Interventions

DRUG

Dato-DXd

DRUG

Durvalumab

DRUG

Paclitaxel

DRUG

Nab-paclitaxel

DRUG

Gemcitabine

DRUG

Carboplatin

DRUG

Pembrolizumab

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Breast Cancer

Locations

Research Site

Daphne, Alabama 36526

United States

Research Site

Springdale, Arkansas 72762

United States

Research Site

Duarte, California 91010

United States

Research Site

Glendale, California 91204

United States

Research Site

Sacramento, California 95817

United States

Research Site

Santa Rosa, California 95403

United States

Research Site

Aurora, Colorado 80012

United States

Research Site

New Haven, Connecticut 06510

United States

Research Site

Jacksonville, Florida 32256

United States

Research Site

Miami, Florida 33176

United States

Research Site

Palm Bay, Florida 32909

United States

Research Site

Plantation, Florida 33324

United States

Research Site

Atlanta, Georgia 30318

United States

Research Site

Honolulu, Hawaii 96819

United States

Research Site

Chicago, Illinois 60637

United States

Research Site

Decatur, Illinois 62526

United States

Research Site

Elmhurst, Illinois 60126

United States

Research Site

Naperville, Illinois 60540

United States

Research Site

New Albany, Indiana 47150

United States

Research Site

Des Moines, Iowa 50309

United States

Research Site

Lexington, Kentucky 40503

United States

Research Site

Louisville, Kentucky 40202

United States

Research Site

Louisville, Kentucky 40207

United States

Research Site

Baton Rouge, Louisiana 70808

United States

Research Site

Baton Rouge, Louisiana 70809

United States

Research Site

Baltimore, Maryland 21215

United States

Research Site

Columbia, Maryland 21044

United States

Research Site

Boston, Massachusetts 02111

United States

Research Site

Worcester, Massachusetts 01655

United States

Research Site

Detroit, Michigan 48201

United States

Research Site

Grand Rapids, Michigan 49503

United States

Research Site

Saint Paul, Minnesota 55109

United States

Research Site

Hattiesburg, Mississippi 39401

United States

Research Site

St Louis, Missouri 63129

United States

Research Site

Albuquerque, New Mexico 87109

United States

Research Site

Albany, New York 12206

United States

Research Site

New York, New York 10065

United States

Research Site

Stony Brook, New York 11794-7263

United States

Research Site

Cincinnati, Ohio 45219

United States

Research Site

Cincinnati, Ohio 45245

United States

Research Site

Cleveland, Ohio 44195

United States

Research Site

York, Pennsylvania 17403

United States

Research Site

Providence, Rhode Island 02903

United States

Research Site

Chattanooga, Tennessee 37404

United States

Research Site

Nashville, Tennessee 37203

United States

Research Site

Dallas, Texas 75230

United States

Research Site

Dallas, Texas 75246

United States

Research Site

Dallas, Texas 75246

United States

Research Site

El Paso, Texas 79902

United States

Research Site

Flower Mound, Texas 75028

United States

Research Site

Fort Worth, Texas 76104

United States

Research Site

Houston, Texas 77054

United States

Research Site

Houston, Texas 77090

United States

Research Site

Houston, Texas 77098

United States

Research Site

Kingwood, Texas 77339

United States

Research Site

McKinney, Texas 75071

United States

Research Site

Sugar Land, Texas 77479

United States

Research Site

Charlottesville, Virginia 22903

United States

Research Site

Fairfax, Virginia 22031

United States

Research Site

Midlothian, Virginia 23114

United States

Research Site

Norfolk, Virginia 23502

United States

Research Site

Roanoke, Virginia 24014

United States

Research Site

Tacoma, Washington 98405

United States

Research Site

Madison, Wisconsin 53792

United States

Research Site

CABA, 1414

Argentina

Research Site

CABA, 1425

Argentina

Research Site

CABA, C1113AAE

Argentina

Research Site

CABA, C1425

Argentina

Research Site

Ciudad Autónoma Buenos Aires, C1430EFA

Argentina

Research Site

Ciudad de Buenos Aires, C1015ABO

Argentina

Research Site

Rosario, 2000

Argentina

Research Site

San Nicolás de los Arroyos, B2900

Argentina

Research Site

Camperdown, 2050

Australia

Research Site

Darlinghurst, 2010

Australia

Research Site

Heidelberg, 3084

Australia

Research Site

Melbourne, 3000

Australia

Research Site

Nedlands, 6009

Australia

Research Site

Waratah, 2298

Australia

Research Site

Barretos, 14784-400

Brazil

Research Site

Curitiba, 80730-150

Brazil

Research Site

Florianópolis, 88034-000

Brazil

Research Site

Goiânia, 74000-000

Brazil

Research Site

Itajaí, 88301-220

Brazil

Research Site

Porto Alegre, 90035-003

Brazil

Research Site

Recife, 52010-075

Brazil

Research Site

São Paulo, 01246-000

Brazil

Research Site

São Paulo, 01317-001

Brazil

Research Site

Teresina, 64049-200

Brazil

Research Site

Barrie, Ontario L4M 6M2

Canada

Research Site

Hamilton, Ontario L8V 5C2

Canada

Research Site

Toronto, Ontario M5G 2M9

Canada

Research Site

Greenfield Park, Quebec J4V 2H1

Canada

Research Site

Montreal, Quebec H2X 0A9

Canada

Research Site

Montreal, Quebec H4A 3J1

Canada

Research Site

Québec, Quebec G1S 4L8

Canada

Research Site

Regina, Saskatchewan S4T 7T1

Canada

Research Site

Saskatoon, Saskatchewan S7N 4H4

Canada

Research Site

Anyang, 455000

China

Research Site

Beijing, 100044

China

Research Site

Beijing, 100142

China

Research Site

Bengbu, 233004

China

Research Site

Changchun, 130021

China

Research Site

Changsha, 410008

China

Research Site

Changsha, 410013

China

Research Site

Chengdu, 610000

China

Research Site

Chengdu, 610041

China

Research Site

Chongqing, 400030

China

Research Site

Fuzhou, 350014

China

Research Site

Guangzhou, 510060

China

Research Site

Guangzhou, 510120

China

Research Site

Guangzhou, 510700

China

Research Site

Hangzhou, 310009

China

Research Site

Hangzhou, 310016

China

Research Site

Hangzhou, 310022

China

Research Site

Harbin, 150081

China

Research Site

Hefei, 230031

China

Research Site

Jinan, 250021

China

Research Site

Meizhou, 514031

China

Research Site

Nanchang, 330009

China

Research Site

Nanjing, 2100008

China

Research Site

Nanjing, 210009

China

Research Site

Nanning, 530021

China

Research Site

Shandong,

China

Research Site

Shanghai, 200025

China

Research Site

Shanghai, 200080

China

Research Site

Shenyang, 110004

China

Research Site

Tianjin, 300000

China

Research Site

Wenzhou, 325000

China

Research Site

Wuhan, 430022

China

Research Site

Wuhan, 430079

China

Research Site

Xi'an, 710061

China

Research Site

Xiamen, 361003

China

Research Site

Xintai, 54031

China

Research Site

Xuzhou, 221009

China

Research Site

Zhanjiang, 524003

China

Research Site

Zhengzhou, 450008

China

Research Site

Zhengzhou, 450052

China

Research Site

Lille, 59000

France

Research Site

Lyon, 69373

France

Research Site

Montpellier, 34298

France

Research Site

Paris, 75020

France

Research Site

Saint-Herblain, 44805

France

Research Site

Toulouse, 31059

France

Research Site

Vandœuvre-lès-Nancy, 54511

France

Research Site

Villejuif, 94800

France

Research Site

Düsseldorf, 40479

Germany

Research Site

Essen, 45136

Germany

Research Site

Georgsmarienhütte, 49124

Germany

Research Site

Hamburg, 20357

Germany

Research Site

Hanover, 30625

Germany

Research Site

Heidelberg, 69120

Germany

Research Site

Heilbronn, 74078

Germany

Research Site

Leipzig, 04103

Germany

Research Site

Hong Kong, 999077

Hong Kong

Research Site

Hong Kong, 999077

Hong Kong

Research Site

Hong Kong,

Hong Kong

Research Site

Shatin, 00000

Hong Kong

Research Site

Calicut, 673601

India

Research Site

Chennai, 600031

India

Research Site

Jaipur, 302004

India

Research Site

Kochi, 682027

India

Research Site

Kolkata, 700160

India

Research Site

Kottayam, 686008

India

Research Site

Marg Jaipur, 302004

India

Research Site

Mohali, 160055

India

Research Site

Mysuru, 570017

India

Research Site

Nagpur, 440001

India

Research Site

Nashik, 422009

India

Research Site

New Delhi, 110075

India

Research Site

New Delhi, 11029

India

Research Site

Puducherry, 605006

India

Research Site

Surat, 395002

India

Research Site

Thiruvananthapuram, 695011

India

Research Site

Vadodara, 391760

India

Research Site

Visakhapatnam, 530053

India

Research Site

Bergamo, 24127

Italy

Research Site

Empoli, 50053

Italy

Research Site

Milan, 20132

Italy

Research Site

Milan, 20141

Italy

Research Site

Modena, 41124

Italy

Research Site

Naples, 80131

Italy

Research Site

Padova, 35128

Italy

Research Site

Reggio Emilia, 42123

Italy

Research Site

Roma, 00168

Italy

Research Site

Rozzano, 20089

Italy

Research Site

Akashi-shi, 673-8558

Japan

Research Site

Bunkyō City, 113-8431

Japan

Research Site

Bunkyō City, 113-8677

Japan

Research Site

Chiba, 260-8717

Japan

Research Site

Chūōku, 104-0045

Japan

Research Site

Fukuoka, 811-1395

Japan

Research Site

Fukushima, 960-1295

Japan

Research Site

Gifu, 501-1194

Japan

Research Site

Hidaka-shi, 350-1298

Japan

Research Site

Hiroshima, 730-8518

Japan

Research Site

Hiroshima, 734-8551

Japan

Research Site

Isehara-shi, 259-1193

Japan

Research Site

Kamogawa-shi, 296-8602

Japan

Research Site

Kashiwa, 277-8577

Japan

Research Site

Kitaadachi-gun, 362-0806

Japan

Research Site

Kōtoku, 135-8550

Japan

Research Site

Kumamoto, 860-8556

Japan

Research Site

Kurume-shi, 830-0011

Japan

Research Site

Matsuyama, 791-0280

Japan

Research Site

Nagoya, 466-8560

Japan

Research Site

Nagoya, 467-8602

Japan

Research Site

Niigata, 951-8566

Japan

Research Site

Nishinomiya-shi, 663-8501

Japan

Research Site

Okayama, 700-8558

Japan

Research Site

Osaka, 541-8567

Japan

Research Site

Osakasayama-shi, 589-8511

Japan

Research Site

Ota-shi, 373-8550

Japan

Research Site

Sapporo, 003-0804

Japan

Research Site

Sendai, 980-8574

Japan

Research Site

Shinagawa-ku, 142-8666

Japan

Research Site

Shinjuku-ku, 160-0023

Japan

Research Site

Shinjuku-ku, 162-8655

Japan

Research Site

Tsu, 514-8507

Japan

Research Site

Tsukuba, 305-8577

Japan

Research Site

Yokohama, 241-8515

Japan

Research Site

CD Mexico, 04980

Mexico

Research Site

Guadalajara, 44638

Mexico

Research Site

Guadalajara, 44670

Mexico

Research Site

Mexico City, 0 3100

Mexico

Research Site

Mexico City, 06760

Mexico

Research Site

México, 04700

Mexico

Research Site

Tuxtla Gutiérrez, 29090

Mexico

Research Site

Bacolod, 6100

Philippines

Research Site

Cebu City, 6000

Philippines

Research Site

City of Muntinlupa, 1780

Philippines

Research Site

Manila, 1000

Philippines

Research Site

Quezon City, 1112

Philippines

Research Site

San Juan City, 1502

Philippines

Research Site

Bialystok, 15-027

Poland

Research Site

Bydgoszcz, 85-796

Poland

Research Site

Gdansk, 80-952

Poland

Research Site

Gdynia, 81-519

Poland

Research Site

Konin, 62-500

Poland

Research Site

Krakow, 31-115

Poland

Research Site

Krakow, 31-501

Poland

Research Site

Legnica, 59-220

Poland

Research Site

Lodz, 90-302

Poland

Research Site

Lublin, 20-090

Poland

Research Site

Przemyśl, 37-700

Poland

Research Site

Warsaw, 02-781

Poland

Research Site

Wroclaw, 53-413

Poland

Research Site

Singapore, 119228

Singapore

Research Site

Singapore, 169610

Singapore

Research Site

Singapore, 217562

Singapore

Research Site

Singapore, 308433

Singapore

Research Site

Cape Town, 7570

South Africa

Research Site

Johannesburg, 2013

South Africa

Research Site

Johannesburg, 2193

South Africa

Research Site

Johannesburg, 2196

South Africa

Research Site

Paarl, 7646

South Africa

Research Site

Pretoria, 0081

South Africa

Research Site

Pretoria, 0081

South Africa

Research Site

Busan, 49241

South Korea

Research Site

Daegu, 41404

South Korea

Research Site

Goyang-si, 10408

South Korea

Research Site

Seongnam-si, 13620

South Korea

Research Site

Seoul, 02841

South Korea

Research Site

Seoul, 03080

South Korea

Research Site

Seoul, 03722

South Korea

Research Site

Seoul, 05505

South Korea

Research Site

Seoul, 06273

South Korea

Research Site

Seoul, 06351

South Korea

Research Site

Seoul, 06591

South Korea

Research Site

Barcelona, 08028

Spain

Research Site

Barcelona, 8035

Spain

Research Site

Granada, 18016

Spain

Research Site

Hospitalet deLlobregat, 08907

Spain

Research Site

Madrid, 28007

Spain

Research Site

Madrid, 28034

Spain

Research Site

Pamplona, 31008

Spain

Research Site

Santander, 39008

Spain

Research Site

Hsinchu, 300

Taiwan

Research Site

Kaohsiung City, 80756

Taiwan

Research Site

Taichung, 40447

Taiwan

Research Site

Tainan, 704

Taiwan

Research Site

Taipei, 100

Taiwan

Research Site

Taipei, 10449

Taiwan

Research Site

Taipei, 11259

Taiwan

Research Site

Taipei, 112

Taiwan

Research Site

Taoyuan, 333

Taiwan

Research Site

Bangkok, 10210

Thailand

Research Site

Bangkok, 10330

Thailand

Research Site

Bangkok, 10400

Thailand

Research Site

Bangkok, 10700

Thailand

Research Site

Chiang Mai, 50200

Thailand

Research Site

Dusit, 10300

Thailand

Research Site

Khon Kaen, 40002

Thailand

Research Site

Songkhla, 90110

Thailand

Research Site

Ankara, 06520

Turkey (Türkiye)

Research Site

Ankara, 6200

Turkey (Türkiye)

Research Site

Besevler Ankara,

Turkey (Türkiye)

Research Site

Istanbul, 34010

Turkey (Türkiye)

Research Site

Izmir, 35575

Turkey (Türkiye)

Research Site

Küçükçekmece, 34295

Turkey (Türkiye)

Research Site

Samsun, 55200

Turkey (Türkiye)

Research Site

Cardiff, CF14 2TL

United Kingdom

Research Site

Chelsea, SW3 6JJ

United Kingdom

Research Site

Leicester, Le5 4PW

United Kingdom

Research Site

Liverpool, L7 8YA

United Kingdom

Research Site

London, EC1A 7BE

United Kingdom

Research Site

London, SW17 0QT

United Kingdom

Research Site

Oxford, OX3 7LE

United Kingdom

Research Site

Surrey, GU2 7XX

United Kingdom

Research Site

Sutton, SM2 5PT

United Kingdom

Research Site

Taunton, TA1 5DA

United Kingdom

Research Site

Da Nang, 550000

Vietnam

Research Site

Hanoi, 100000

Vietnam

Research Site

Ho Chi Minh City, 700000

Vietnam

Research Site

Hồ Chí Minh, 700000

Vietnam

Research Site

Huế, 530000

Vietnam

Research Site

Viet Tri, 35000

Vietnam

Research Site

Vinh, 460000

Vietnam