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NCT06966453PHASE1, PHASE2Recruiting

A Study of Disitamab Vedotin in Adults With HER2 Expressing Advanced Breast Cancer

Pfizer

Start Date

6/30/2025

Completion Date

1/27/2030

Summary

The purpose of this clinical study is to learn about the safety and effects of the study medicine (called disitamab vedotin) for the possible treatment of people with breast cancer that is hard to treat and has spread in the body (advanced cancer). This study is seeking participants who: * have breast cancer that is hard to treat and has spread in the body (advanced cancer) * have tumors that have HER2 on them * have received previous treatment for their advanced breast cancer All participants in this study will receive disitamab vedotin at the study clinic once every 2 weeks as an intravenous (IV) infusion (given directly into a vein). Participants will take the study medicine until they or their doctor decides to stop. This might be because their cancer is getting worse, the study medicine is no longer helping, they have bad side effects, or they wish to stop taking the study medicine. During this time, the participants will have study visits every 2 weeks. After the participants have stopped taking the study medicine, they will have follow-up visits about every 6 weeks unless their cancer gets worse. After that, they will have follow-up phone calls about every 12 weeks. The study team will look at the experiences of people receiving the study medicine. This will help the study team decide if the study medicine is safe and effective.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of locally-advanced, unresectable, or metastatic breast carcinoma. * Human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status appropriate for enrollment in cohort. * HER2 status determined by most recent local assessment based on American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) guidelines for assessment of HER2 in BC for interpretation of HER2 expression and amplification * HER2+: immunohistochemistry (IHC) 3+ or IHC 2+/in situ hybridization (ISH)+ * HER2-low: IHC 1+/ISH-negative or untested or IHC 2+/ISH-negative * HER2-ultralow: IHC 0 with membrane staining (any staining of the membrane in \>0 and ≤10% of cancer cells) o HR+ disease is determined as either estrogen receptor (ER) and/or progesterone receptor (PgR) positive \[ER or PgR ≥1%\]) and HR negative disease is determined as both ER and PR negative \[ER and PgR \<1%\]) per ASCO/CAP guidelines in the advanced disease setting. If a patient has had multiple ER/PgR results for advanced disease, the most recent test result will be used to confirm eligibility. Prior therapy requirements for Cohort 1 (HER2+, HR+ or HR- participants): * Received prior trastuzumab, pertuzumab and a taxane if available as local first line standard of care therapy for advanced disease. * Prior tucatinib based therapy is allowed. * Must have progression on or after, or be intolerant to, T-DXd in any line advanced disease setting. * No more than 3 prior systemic cytotoxic therapy regimens (including antibody drug conjugates \[ADCs\]) for Locally Advanced (LA)/metastatic breast cancer (mBC). Participants previously treated with (neo)adjuvant cytotoxic therapy and have disease relapsed within 6 months of cytotoxic treatment is considered to have received 1 line of cytotoxic therapy for LA/mBC. Prior therapy requirements for Cohort 2 (HR+/HER2-low participants): * No more than 3 prior systemic cytotoxic therapy regimens (including ADCs) for LA/mBC. Participants previously treated with (neo)adjuvant cytotoxic therapy and have disease relapsed within 6 months of cytotoxic treatment is considered to have received 1 line of cytotoxic therapy for LA/mBC. * Participants with known germline breast cancer gene (BRCA) mutation must have received a poly-ADP ribose polymerase (PARP) inhibitor, where available and not medically contraindicated. * Must have progression on or after, or be intolerant to, trastuzumab deruxtecan (T-DXd) in any line advanced disease setting. * Must have intolerance to endocrine therapy (ET) or ET refractory disease: * Progressed on ≥2 lines of ET for LA/mBC AND had received a cyclin-dependent kinase (CDK)4/6 inhibitor in the adjuvant or metastatic setting if available as local standard of care and not contraindicated. OR • Progressed on 1 line of ET for LA/mBC AND had a relapse while on adjuvant ET after definitive surgery for primary tumor AND had received a cyclin-dependent kinase (CDK) 4/6 inhibitor in the adjuvant or advanced setting if available as local standard of care and not contraindicated. Prior therapy requirements for Cohort 3 (HR+/HER2-ultralow or HR-/HER2-low \[HER2 low TNBC\] participants): * No more than 4 prior systemic cytotoxic chemotherapy regimens (including ADCs) for advanced or mBC. Participants previously treated with (neo)adjuvant cytotoxic therapy and have disease relapsed within 6 months of cytotoxic treatment is considered to have received 1 line of cytotoxic therapy for LA/mBC. * Known germline BRCA mutation must have received a PARP-inhibitor if available as local standard of care therapy and not medically contraindicated. * Prior sacituzumab govitecan is allowed. * Prior T-DXd is allowed. * Participants with HR negative (TNBC), HER2-low and programmed cell death receptor ligand 1 (PD-L1)-positive (combined positive score \[CPS\] ≥10) tumors must have received pembrolizumab (or other PD-L1 inhibitor) with chemotherapy if available as local standard of care therapy and not medically contraindicated. * Participants with HR+/HER2-ultra low tumors must have received at least 1 antihormonal therapy in any setting or be ineligible for ET. * Participants with HR+/HER2-ultra low tumors must have had prior therapy with a CDK4/6 inhibitor in the adjuvant or advanced setting. Exclusion Criteria: * Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin. * Active central nervous system (CNS) and/or leptomeningeal metastasis. * Participants with a history of other invasive malignancy within 3 years before the Cycle 1 Day 1 (C1D1) of study intervention, or any evidence of residual disease from a previously diagnosed malignancy. * Prior therapy with ADCs with MMAE payload. * Participants who have received prior systemic anticancer treatment or radiotherapy within 2 weeks, or 5 half-lives, whichever is shorter, prior to C1D1 of study intervention. Note: If the last immediate anticancer treatment contained an antibody-based agent(s), then an interval of 28 days or 5 half-lives (whichever is shorter) of the agent(s) prior to receiving the study intervention treatment is required. * Participants must have recovered from all adverse events due to previous therapies.

Interventions

DRUG

Disitamab vedotin

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Conditions

Breast CancerBreast Neoplasms

Locations

Southern Cancer Center, PC

Daphne, Alabama 36526

United States

Southern Cancer Center, PC

Foley, Alabama 36535

United States

Southern Cancer Center, PC

Mobile, Alabama 36608

United States

Banner Gateway Medical Center

Gilbert, Arizona 85234

United States

Banner MD Anderson Cancer Center

Gilbert, Arizona 85234

United States

Los Angeles Cancer Network - Anaheim

Anaheim, California 92805

United States

City of Hope National Medical Center

Duarte, California 91010

United States

Los Angeles Cancer Network

Fountain Valley, California 92708

United States

Los Angeles Hematology Oncology Medical Group

Glendale, California 91204

United States

City of Hope at Irvine Lennar

Irvine, California 92618

United States

Los Angeles Cancer Network

Los Angeles, California 90017

United States

Valkyrie Clinical Trials

Los Angeles, California 90067

United States

Mission Community Hospital (Satellite Site)

Los Angeles, California 91402

United States

Clinical and Translational Research Unit (CTRU)

Palo Alto, California 94304

United States

Stanford Cancer Center

Palo Alto, California 94304

United States

Stanford Women's Cancer Center

Palo Alto, California 94304

United States

Stanford Health Care, Investigational Drug Service

Stanford, California 94305

United States

Los Angeles Hematology Oncology Medical Group

Van Nuys, California 91405

United States

Rocky Mountain Cancer Centers, LLP

Aurora, Colorado 80012

United States

Rocky Mountain Cancer Centers, LLP

Boulder, Colorado 80303

United States

Rocky Mountain Cancer Centers, LLP

Centennial, Colorado 80112

United States

Rocky Mountain Cancer Centers, LLP

Colorado Springs, Colorado 80907

United States

Rocky Mountain Cancer Centers, LLP

Colorado Springs, Colorado 80923

United States

Rocky Mountain Cancer Centers, LLP

Denver, Colorado 80220

United States

Rocky Mountain Cancer Centers, LLP

Englewood, Colorado 80113

United States

Rocky Mountain Cancer Centers, LLP

Lakewood, Colorado 80228

United States

Rocky Mountain Cancer Centers, LLP

Littleton, Colorado 80120

United States

Rocky Mountain Cancer Centers, LLP

Lone Tree, Colorado 80124

United States

Rocky Mountain Cancer Centers, LLP

Longmont, Colorado 80504

United States

Rocky Mountain Cancer Centers, LLP

Pueblo, Colorado 81003

United States

Rocky Mountain Cancer Centers, LLP

Thornton, Colorado 80260

United States

Smilow Cancer Hospital - Derby

Derby, Connecticut 06418

United States

Smilow Cancer Hospital - Fairfield

Fairfield, Connecticut 06824

United States

Smilow Cancer Hospital - Glastonbury

Glastonbury, Connecticut 06033

United States

Smilow Cancer Hospital - Greenwich

Greenwich, Connecticut 06830

United States

Smilow Cancer Hospital - Guilford

Guilford, Connecticut 06437

United States

Smilow Cancer Hospital at St. Francis

Hartford, Connecticut 06105

United States

Smilow Cancer Hospital - Yale New Haven Health

New Haven, Connecticut 06510

United States

Yale-New Haven Hospital

New Haven, Connecticut 06510

United States

Yale University - Smilow Cancer Hospital; C/O Thomas Ferencz, RPh, BCOP

New Haven, Connecticut 06511

United States

Yale School of Medicine

New Haven, Connecticut 06520

United States

Smilow Cancer Hospital - North Haven

North Haven, Connecticut 06473

United States

Smilow Cancer Hospital - Long Ridge

Stamford, Connecticut 06902

United States

Smilow Cancer Hospital - Torrington

Torrington, Connecticut 06790

United States

Smilow Cancer Hospital - Trumbull

Trumbull, Connecticut 06611

United States

Smilow Cancer Hospital - Waterbury

Waterbury, Connecticut 06708

United States

Smilow Cancer Hospital - Waterford

Waterford, Connecticut 06385

United States

Georgetown University Medical Center - Department of Pharmacy, Oncology Pharmacy

Washington D.C., District of Columbia 20007

United States

Georgetown University Medical Center

Washington D.C., District of Columbia 20007

United States

Medstar Georgetown University Hospital

Washington D.C., District of Columbia 20007

United States

Florida Cancer Specialists

Clearwater, Florida 33761

United States

Sylvester Comprehensive Cancer Center - The Lennar Foundation Medical Center

Coral Gables, Florida 33146

United States

Sylvester Comprehensive Cancer Center - Coral Springs

Coral Springs, Florida 33065

United States

University of Miami Hospital and Clinics - Deerfield Beach

Deerfield Beach, Florida 33442

United States

Sylvester Comprehensive Cancer Center- Doral

Doral, Florida 33166

United States

Florida Cancer Specialists

Gainesville, Florida 32605

United States

Sylvester Comprehensive Cancer Center - Hollywood

Hollywood, Florida 33021

United States

Florida Cancer Specialists

Largo, Florida 33770

United States

Florida Cancer Specialists

Lecanto, Florida 34461

United States

Sylvester Comprehensive Cancer Center

Miami, Florida 33136

United States

University of Miami Hospital and Clinics

Miami, Florida 33136

United States

Sylvester Comprehensive Cancer Center - Kendall

Miami, Florida 33176

United States

Sylvester Comprehensive Cancer Center - Sole Mia

North Miami, Florida 33181

United States

Florida Cancer Specialists

Ocala, Florida 34474

United States

Florida Cancer Specialists

Orange City, Florida 32763

United States

Florida Cancer Specialists

Orlando, Florida 32806

United States

Sylvester Comprehensive Cancer Center - Plantation

Plantation, Florida 33324

United States

Florida Cancer Specialists

St. Petersburg, Florida 33705

United States

Florida Cancer Specialists

Tallahassee, Florida 32308

United States

Florida Cancer Specialists

Tampa, Florida 33607

United States

Florida Cancer Specialists

Tavares, Florida 32778

United States

Florida Cancer Specialists

The Villages, Florida 32159

United States

Florida Cancer Specialists

Trinity, Florida 34655

United States

Florida Cancer Specialists

West Palm Beach, Florida 33401

United States

Florida Cancer Specialists

Winter Park, Florida 32789

United States

Winship Cancer Institute @ Emory University Hospital Midtown

Atlanta, Georgia 30308

United States

Emory Clinic Investigational Drug Services

Atlanta, Georgia 30322

United States

Emory University Hospital

Atlanta, Georgia 30322

United States

Winship Cancer Institute

Atlanta, Georgia 30322

United States

Oncology Associates of Oregon, P.C.

Albany, Oregon 97321

United States

Oncology Associates of Oregon, P.C.

Corvallis, Oregon 97330

United States

Oncology Associates of Oregon, P.C.

Eugene, Oregon 97401

United States

Oncology Associates of Oregon, P.C.

Springfield, Oregon 97477

United States

Alliance Cancer Specialists, PC

Bensalem, Pennsylvania 19020

United States

Alliance Cancer Specialists, PC

Doylestown, Pennsylvania 18901

United States

Alliance Cancer Specialists, PC

Horsham, Pennsylvania 19044

United States

Alliance Cancer Specialists, PC

Langhorne, Pennsylvania 19047

United States

Alliance Cancer Specialists, PC

Media, Pennsylvania 19063

United States

Alliance Cancer Specialists, PC

Sellersville, Pennsylvania 18960

United States

Alliance Cancer Specialists, PC

Wynnewood, Pennsylvania 19096

United States

Sarah Cannon Research Institute - Pharmacy

Nashville, Tennessee 37203

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

Texas Oncology-Northeast Texas

Allen, Texas 75013

United States

Texas Oncology - DFW

Arlington, Texas 76012

United States

Texas Oncology - DFW

Arlington, Texas 76014

United States

Texas Oncology - DFW

Bedford, Texas 76022

United States

Texas Oncology - DFW

Dallas, Texas 75203

United States

Texas Oncology - DFW

Dallas, Texas 75230

United States

Texas Oncology - DFW

Dallas, Texas 75231

United States

Texas Oncology - DFW

Dallas, Texas 75237

United States

Texas Oncology - DFW

Dallas, Texas 75246

United States

Texas Oncology-Northeast Texas

Denison, Texas 75020

United States

Texas Oncology-Northeast Texas

Denton, Texas 76201

United States

Texas Oncology-Northeast Texas

Flower Mound, Texas 75028

United States

Texas Oncology - DFW

Fort Worth, Texas 76104

United States

Texas Oncology - DFW

Grapevine, Texas 76051

United States

US Oncology Investigation Products Center(IPC)

Irving, Texas 75063

United States

US Oncology Investigational Product Center (IPC)

Irving, Texas 75063

United States

Texas Oncology-Northeast Texas

Lewisville, Texas 75056

United States

Texas Oncology-Northeast Texas

Longview, Texas 75601

United States

Texas Oncology-Northeast Texas

McKinney, Texas 75071

United States

Texas Oncology-Northeast Texas

Palestine, Texas 75801

United States

Texas Oncology-Northeast Texas

Paris, Texas 75460

United States

Texas Oncology - DFW

Plano, Texas 75075

United States

Texas Oncology - DFW

Plano, Texas 75093

United States

Texas Oncology - San Antonio

San Antonio, Texas 78217

United States

Texas Oncology - San Antonio

San Antonio, Texas 78240

United States

Texas Oncology-Northeast Texas

Tyler, Texas 75702

United States

Virginia Cancer Specialists, PC

Arlington, Virginia 22201

United States

Oncology & Hematology Associates of Southwest Virginia Inc dba Blue Ridge Cancer Care

Blacksburg, Virginia 24060

United States

Virginia Oncology Associates

Chesapeake, Virginia 23320

United States

Virginia Cancer Specialists, PC

Fairfax, Virginia 22031

United States

Oncology & Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care

Low Moor, Virginia 24457

United States

Virginia Cancer Specialists, PC

Manassas, Virginia 20110

United States

Virginia Oncology Associates

Newport News, Virginia 23606

United States

Virginia Oncology Associates

Norfolk, Virginia 23502

United States

Virginia Cancer Specialists, PC

Reston, Virginia 20190

United States

Oncology & Hematology Associates of Southwest Virginia Inc dba Blue Ridge Cancer Care

Roanoke, Virginia 24014

United States

Oncology & Hematology Associates of Southwest Virginia Inc dba Blue Ridge Cancer Care

Salem, Virginia 24153

United States

Virginia Oncology Associates

Virginia Beach, Virginia 23456

United States

Virginia Oncology Associates

Williamsburg, Virginia 23188

United States

Oncology & Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care

Wytheville, Virginia 24382

United States

Swedish Cancer Institute

Seattle, Washington 98104

United States

Swedish Medical Center

Seattle, Washington 98122

United States

Blacktown Hospital

Blacktown, New South Wales 2148

Australia

Royal Brisbane and Women's Hospital

Brisbane, Queensland 4029

Australia

Western Health-Sunshine & Footscray Hospitals

St Albans, Victoria 3021

Australia

ANIMI - Unidade de Tratamento Oncologico

Lages, Santa Catarina 88501001

Brazil

Centro de Oncologia - CEON+ - Unidade São Caetano do Sul

São Caetano do Sul, São Paulo 09541-270

Brazil

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta T2N 5G2

Canada

Waterloo Regional Health Network

Kitchener, Ontario N2G 1G3

Canada

Lakeridge Health

Oshawa, Ontario L1G 2B9

Canada

Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung

Essen, North Rhine-Westphalia 45136

Germany

University Hospital Carl Gustav Carus, Technical University Dresden

Dresden, Saxony 01307

Germany

Charité University Hospital Berlin

Berlin, 10117

Germany

Universitätsklinikum Heidelberg

Heidelberg, 69120

Germany

Universitätsklinikum Leipzig

Leipzig, 04103

Germany

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Naples, Campania 80131

Italy

Azienda Ospedaliero-Universitaria di Bologna IRCCS

Bologna, Emilia-Romagna 40138

Italy

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"

Meldola, Emilia-Romagna 47014

Italy

Cro-Irccs

Aviano, Friuli Venezia Giulia 33081

Italy

Azienda USL Toscana Nord Ovest_Ospedale Civile di Livorno

Livorno, Tuscany 57124

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168

Italy

Aichi Cancer Center

Nagoya, Aichi-ken 464-8681

Japan

Kanagawa cancer center

Yokohama, Kanagawa 2418515

Japan

The University of Osaka Hospital

Suita, Osaka 565-0871

Japan

National Cancer Center Hospital

Chuo-ku, Tokyo 104-0045

Japan

The Cancer Institute Hospital of JFCR

Koto, Tokyo 135-8550

Japan

Pan American Center for Oncology Trials, LLC

Rio Piedras, 00935

Puerto Rico

Parc de Salut Mar - Hospital del Mar

Barcelona, Barcelona [barcelona] 08003

Spain

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [barcelona] 08035

Spain

Hospital Universitario La Paz

Madrid, Madrid, Comunidad de 28046

Spain

Hospital Universitario Virgen de la Victoria

Málaga, Málaga 29010

Spain

Hospital Clinico de Valencia

Valencia, Valenciana, Comunitat 46010

Spain

Hospital Universitario Virgen Nieves

Granada, 18012

Spain

Hospital Beata María Ana

Madrid, 28007

Spain