Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

100

participants targeted

Target at P75+ for phase_1 breast-cancer

Timeline

46mo left

Started Jun 2025

Typical duration for phase_1 breast-cancer

Geographic Reach

9 countries

166 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.6 years study duration

Study Progress19%

Jun 2025Jan 2030

First Submitted

Initial submission to the registry

May 9, 2025

Completed

2 days until next milestone

First Posted

Study publicly available on registry

May 11, 2025

Completed

2 months until next milestone

Study Start

First participant enrolled

June 30, 2025

Completed

2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 25, 2027

Expected

2.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 27, 2030

Last Updated

April 21, 2026

Status Verified

April 1, 2026

Enrollment Period

2.3 years

First QC Date

May 9, 2025

Last Update Submit

April 20, 2026

Conditions

Breast Cancer Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

Objective response (OR) by investigator assessment
The primary endpoint OR by investigator assessment is defined as the proportion of participants with confirmed CR or PR as determined by investigator per RECIST Version 1.1.
From Cycle 1 Day 1 until disease progression by investigator assessment per RECIST version 1.1, or death due to any cause, whichever is earlier; up to approximately 2 years

Secondary Outcomes (7)

Duration of response (DOR) per RECIST v1.1 by investigator assessment
From first documentation of objective response (CR or PR) by investigator assessment per RECIST version 1.1 that is subsequently confirmed, to the first documentation of progressive disease or to death due to any cause; up to approximately 2 years
Disease control rate (DCR) (confirmed CR, confirmed PR, and stable disease) per RECIST v1.1 by investigator assessment
From Cycle 1 Day 1 until disease progression by investigator assessment per RECIST version 1.1, or death due to any cause, whichever is earlier; up to approximately 2 years
Progression-free survival (PFS) per RECIST v1.1 by investigator assessment
From Cycle 1 Day 1 until disease progression by investigator assessment per RECIST version 1.1, or death due to any cause, whichever is earlier; ; up to approximately 2 years
Overall survival (OS)
From Cycle 1 Day 1 until death due to any cause; up to approximately 3 years
PK Parameter: Serum Concentrations of disitamab vedotin, total antibody, and unconjugated MMAE
From Cycle 1 Day 1 to end of treatment; up to approximately 2 years
+2 more secondary outcomes

Study Arms (3)

Cohort 1: HER2+ locally advanced or metastatic breast cancer

EXPERIMENTAL

disitamab vedotin monotherapy

Drug: Disitamab vedotin

Cohort 2: HR+, HER2-low locally advanced or metastatic breast cancer

EXPERIMENTAL

disitamab vedotin monotherapy

Drug: Disitamab vedotin

Cohort 3: HR+, HER2 ultra-low or HR-negative, HER2-low locally advanced or metastatic breast cancer

EXPERIMENTAL

disitamab vedotin monotherapy

Drug: Disitamab vedotin

Interventions

Disitamab vedotinDRUG

Given into the vein (IV; intravenous) every 2 weeks.

Also known as: RC48, RC48-ADC

Cohort 1: HER2+ locally advanced or metastatic breast cancerCohort 2: HR+, HER2-low locally advanced or metastatic breast cancerCohort 3: HR+, HER2 ultra-low or HR-negative, HER2-low locally advanced or metastatic breast cancer

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.
+11 more criteria

You may not qualify if:

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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Pfizerlead

Study Sites (166)

Southern Cancer Center, PC

Daphne, Alabama, 36526, United States

RECRUITING

Southern Cancer Center, PC

Foley, Alabama, 36535, United States

RECRUITING

Southern Cancer Center, PC

Mobile, Alabama, 36608, United States

RECRUITING

Banner Gateway Medical Center

Gilbert, Arizona, 85234, United States

NOT YET RECRUITING

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

NOT YET RECRUITING

Los Angeles Cancer Network - Anaheim

Anaheim, California, 92805, United States

RECRUITING

City of Hope National Medical Center

Duarte, California, 91010, United States

NOT YET RECRUITING

Los Angeles Cancer Network

Fountain Valley, California, 92708, United States

RECRUITING

Los Angeles Hematology Oncology Medical Group

Glendale, California, 91204, United States

RECRUITING

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

NOT YET RECRUITING

Los Angeles Cancer Network

Los Angeles, California, 90017, United States

RECRUITING

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

RECRUITING

Mission Community Hospital (Satellite Site)

Los Angeles, California, 91402, United States

RECRUITING

Clinical and Translational Research Unit (CTRU)

Palo Alto, California, 94304, United States

RECRUITING

Stanford Cancer Center

Palo Alto, California, 94304, United States

RECRUITING

Stanford Women's Cancer Center

Palo Alto, California, 94304, United States

RECRUITING

Stanford Health Care, Investigational Drug Service

Stanford, California, 94305, United States

RECRUITING

Los Angeles Hematology Oncology Medical Group

Van Nuys, California, 91405, United States

RECRUITING