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

Launched by PFIZER · May 9, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new medicine called disitamab vedotin to see how safe and effective it is for treating adults with advanced breast cancer that has spread in the body. Specifically, it focuses on patients whose tumors have a certain protein called HER2. To participate, individuals must have advanced breast cancer that has not responded well to previous treatments, and their tumors must meet specific HER2 testing criteria.

Participants in the study will receive disitamab vedotin through an IV (a small tube placed in a vein) once every two weeks. They will continue receiving the medicine until either their cancer worsens, they experience significant side effects, or they decide to stop. Throughout the trial, participants will have regular check-ups every two weeks, and after stopping the treatment, they will have follow-up visits every six weeks, with additional phone calls every three months. This study is important because it aims to gather information that could help improve treatment options for people with advanced breast cancer.

Gender

ALL

Eligibility 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.