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

Purpose

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.

Conditions

  • Breast Cancer
  • Breast Neoplasms

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort 1: HER2+ locally advanced or metastatic breast cancer 		disitamab vedotin monotherapy
  • Drug: Disitamab vedotin
    Given into the vein (IV; intravenous) every 2 weeks.
    Other names:
    • RC48
    • RC48-ADC
Experimental
Cohort 2: HR+, HER2-low locally advanced or metastatic breast cancer 		disitamab vedotin monotherapy
  • Drug: Disitamab vedotin
    Given into the vein (IV; intravenous) every 2 weeks.
    Other names:
    • RC48
    • RC48-ADC
Experimental
Cohort 3: HR+, HER2 ultra-low or HR-negative, HER2-low locally advanced or metastatic breast cancer 		disitamab vedotin monotherapy
  • Drug: Disitamab vedotin
    Given into the vein (IV; intravenous) every 2 weeks.
    Other names:
    • RC48
    • RC48-ADC

Recruiting Locations

Los Angeles Cancer Network
Fountain Valley 5350207, California 5332921 92708

Los Angeles Cancer Network
Fountain Valley 5350207, California 5332921 92801

Los Angeles Hematology Oncology Medical Group
Glendale 5352423, California 5332921 91204

Los Angeles Cancer Network
Los Angeles 5368361, California 5332921 90017

Valkyrie Clinical Trials
Los Angeles 5368361, California 5332921 90067

Mission Community Hospital (Satellite Site)
Los Angeles 5368361, California 5332921 91402

Clinical and Translational Research Unit (CTRU)
Palo Alto 5380748, California 5332921 94304

Stanford Cancer Center
Palo Alto 5380748, California 5332921 94304

Stanford Women's Cancer Center
Palo Alto 5380748, California 5332921 94304

Stanford Health Care, Investigational Drug Service
Stanford 5398563, California 5332921 94305

Los Angeles Hematology Oncology Medical Group
Van Nuys 5405693, California 5332921 91405

Rocky Mountain Cancer Centers, LLP
Aurora 5412347, Colorado 5417618 80012

Rocky Mountain Cancer Centers, LLP
Boulder 5574991, Colorado 5417618 80303

Rocky Mountain Cancer Centers, LLP
Centennial 5416541, Colorado 5417618 80112

Rocky Mountain Cancer Centers, LLP
Colorado Springs 5417598, Colorado 5417618 80907

Rocky Mountain Cancer Centers, LLP
Colorado Springs 5417598, Colorado 5417618 80923

Rocky Mountain Cancer Centers, LLP
Denver 5419384, Colorado 5417618 80220

Rocky Mountain Cancer Centers, LLP
Englewood 5421250, Colorado 5417618 80113

Rocky Mountain Cancer Centers, LLP
Lakewood 5427946, Colorado 5417618 80228

Rocky Mountain Cancer Centers, LLP
Littleton 5429032, Colorado 5417618 80120

Rocky Mountain Cancer Centers, LLP
Lone Tree 5429208, Colorado 5417618 80124

Rocky Mountain Cancer Centers, LLP
Longmont 5579276, Colorado 5417618 80504

Rocky Mountain Cancer Centers, LLP
Pueblo 5435464, Colorado 5417618 81003

Rocky Mountain Cancer Centers, LLP
Thornton 5441492, Colorado 5417618 80260

Alliance Cancer Specialists, PC
Bensalem 5179995, Pennsylvania 6254927 19020

Alliance Cancer Specialists, PC
Doylestown 5187247, Pennsylvania 6254927 18901

Alliance Cancer Specialists, PC
Horsham 5194302, Pennsylvania 6254927 19044

Alliance Cancer Specialists, PC
Langhorne 5197140, Pennsylvania 6254927 19047

Alliance Cancer Specialists, PC
Media 4559575, Pennsylvania 6254927 19063

Alliance Cancer Specialists, PC
Sellersville 5211420, Pennsylvania 6254927 18960

Alliance Cancer Specialists, PC
Wynnewood 5220230, Pennsylvania 6254927 19096

Sarah Cannon Research Institute - Pharmacy
Nashville 4644585, Tennessee 4662168 37203

SCRI Oncology Partners
Nashville 4644585, Tennessee 4662168 37203

Texas Oncology-Northeast Texas
Allen 4670300, Texas 4736286 75013

Texas Oncology - DFW
Arlington 4671240, Texas 4736286 76012

Texas Oncology - DFW
Arlington 4671240, Texas 4736286 76014

Texas Oncology - DFW
Bedford 4673094, Texas 4736286 76022

Texas Oncology - DFW
Dallas 4684888, Texas 4736286 75203

Texas Oncology - DFW
Dallas 4684888, Texas 4736286 75230

Texas Oncology - DFW
Dallas 4684888, Texas 4736286 75231

Texas Oncology - DFW
Dallas 4684888, Texas 4736286 75237

Texas Oncology - DFW
Dallas 4684888, Texas 4736286 75246

Texas Oncology-Northeast Texas
Denison 4685892, Texas 4736286 75020

Texas Oncology-Northeast Texas
Denton 4685907, Texas 4736286 76201

Texas Oncology-Northeast Texas
Flower Mound 4691585, Texas 4736286 75028

Texas Oncology - DFW
Fort Worth 4691930, Texas 4736286 76104

Texas Oncology - DFW
Grapevine 4694568, Texas 4736286 76051

US Oncology Investigation Products Center(IPC)
Irving 4700168, Texas 4736286 75063

US Oncology Investigational Product Center (IPC)
Irving 4700168, Texas 4736286 75063

Texas Oncology-Northeast Texas
Lewisville 4706057, Texas 4736286 75056

Texas Oncology-Northeast Texas
Longview 4707814, Texas 4736286 75601

Texas Oncology-Northeast Texas
McKinney 4710178, Texas 4736286 75071

Texas Oncology-Northeast Texas
Palestine 4717232, Texas 4736286 75801

Texas Oncology - Northeast Texas
Paris 4717560, Texas 4736286 75460

Texas Oncology-Northeast Texas
Paris 4717560, Texas 4736286 75460

Texas Oncology - DFW
Plano 4719457, Texas 4736286 75075

Texas Oncology - DFW
Plano 4719457, Texas 4736286 75093

Texas Oncology - San Antonio Medical Center
San Antonio 4726206, Texas 4736286 78217

Texas Oncology - San Antonio
San Antonio 4726206, Texas 4736286 78217

Texas Oncology - San Antonio Medical Center
San Antonio 4726206, Texas 4736286 78240

Texas Oncology - San Antonio
San Antonio 4726206, Texas 4736286 78240

Texas Oncology - Northeast Texas
Tyler 4738214, Texas 4736286 75702

Virginia Cancer Specialists, PC
Arlington 4744709, Virginia 6254928 22201

Oncology & Hematology Associates of Southwest Virginia Inc dba Blue Ridge Cancer Care
Blacksburg 4747845, Virginia 6254928 24060

Virginia Oncology Associates
Chesapeake 4752186, Virginia 6254928 23320

Virginia Cancer Specialists, PC
Fairfax 4758023, Virginia 6254928 22031

Oncology & Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care
Low Moor 4770856, Virginia 6254928 24457

Virginia Cancer Specialists, PC
Manassas 4771401, Virginia 6254928 20110

Virginia Oncology Associates
Newport News 4776024, Virginia 6254928 23606

Virginia Oncology Associates
Norfolk 4776222, Virginia 6254928 23502

Virginia Cancer Specialists, PC
Reston 4781530, Virginia 6254928 20190

Oncology & Hematology Associates of Southwest Virginia Inc dba Blue Ridge Cancer Care
Roanoke 4782167, Virginia 6254928 24014

Oncology & Hematology Associates of Southwest Virginia Inc dba Blue Ridge Cancer Care
Salem 4784112, Virginia 6254928 24153

Virginia Oncology Associates
Virginia Beach 4791259, Virginia 6254928 23456

Virginia Oncology Associates
Williamsburg 4793846, Virginia 6254928 23188

Oncology & Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care
Wytheville 4794837, Virginia 6254928 24382

Pan American Center for Oncology Trials, LLC
Rio Piedras 4829037, Puerto Rico 00935

More Details

Status
Recruiting
Sponsor
Pfizer

Study Contact

Pfizer CT.gov Call Center
1-800-718-1021
ClinicalTrials.gov_Inquiries@pfizer.com