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Disitamab vedotin for adults with HER2-expressing advanced breast cancer

A PHASE 1b/2, OPEN-LABEL, MULTICOHORT STUDY OF DISITAMAB VEDOTIN IN ADULTS WITH HER2 EXPRESSING ADVANCED BREAST CANCER

Phase1; Phase2 Interventional Pfizer · NCT06966453

This study will test disitamab vedotin given by IV every two weeks to see if it is safe and helps adults whose HER2-expressing advanced breast cancer has progressed after prior treatment.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment100 (estimated)
Ages18 Years and up
SexAll
SponsorPfizer Industry-sponsored
Drugs / interventionstrastuzumab, pertuzumab, sacituzumab, pembrolizumab, disitamab, tucatinib, chemotherapy
Locations166 sites (Daphne, Alabama and 165 other locations)
Trial IDNCT06966453 on ClinicalTrials.gov

What this trial studies

This phase 1/2 open-label study gives all participants disitamab vedotin by intravenous infusion every two weeks and follows them with clinic visits at the same interval. Participants are enrolled into cohorts based on the level of HER2 expression (HER2+, HER2-low, or HER2-ultralow) and prior treatment history. Treatment continues until disease progression, unacceptable side effects, or patient/physician decision to stop. The trial primarily monitors safety and side effects while also tracking tumor responses and duration of benefit.

Who should consider this trial

Good fit: Adults with histologically or cytologically confirmed locally advanced, unresectable, or metastatic breast cancer whose tumors show HER2 expression (HER2+, HER2-low, or HER2-ultralow) and who have received prior therapy for advanced disease are the intended participants.

Not a fit: Patients whose tumors lack HER2 expression, who cannot tolerate intravenous anti-cancer therapy, or who have uncontrolled medical conditions are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, disitamab vedotin could provide a new targeted treatment option that controls disease and delays progression for people with HER2-expressing advanced breast cancer, including some with low levels of HER2.

How similar studies have performed: Other antibody–drug conjugates targeting HER2—most notably trastuzumab deruxtecan—have shown strong activity in HER2-positive and HER2-low breast cancer, and early studies of disitamab vedotin have reported promising activity, though larger confirmatory trials are still ongoing.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Daphne, Alabama and 165 other locations

+116 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
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Conditions Breast CancerBreast Neoplasms
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.