Locally-advanced, unresectable, or metastatic breast cancer
Conditions
Interventions
* Drug: Disitamab vedotin
- Given into the vein (IV
intravenous) every 2 weeks.
- Other Names:
RC48
RC48-ADC
Sponsors
Kawai Norisuke
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria * Histologically or cytologically confirmed diagnosis of locally-advanced, unresectable, or metastatic breast carcinoma. * HER2 and 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 1. HER2+, IHC 3+ or IHC 2+/ISH+ 2. HER2-low: IHC 1+/ISH-negative or untested or IHC 2+/ISH-negative 3. HER2-ultralow: IHC 0 with membrane staining (any staining of the membrane in >0 and =1%] and HR negative disease is determined as both ER and PR negative [ER and PgR =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 2. 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 CDK4/6 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 sacitu
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * Objective response (OR) by investigator assessment [Time Frame: 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] - 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| * Duration of response (DOR) per RECIST v1.1 by investigator assessment [Time Frame: 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] - DOR by investigator assessment is defined as the time 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, whichever comes first. * Disease control rate (DCR) (confirmed CR, confirmed PR, and stable disease) per RECIST v1.1 by investigator assessment [Time Frame: 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] - DCR by investigator assessment is defined as the proportion of participants with CR or PR with confirmation, or SD by investigator assessment per RECIST version 1.1. * Progression-free survival (PFS) per RECIST v1.1 by investigator assessment [Time Frame: 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] - PFS by investigator assessment is defined as the time from C1D1 to the first documentation of disease progression as determined by investigator per RECIST version 1.1, or to death due to any cause, whichever comes first. * Overall survival (OS) [Time Frame: From Cycle 1 Day 1 until death due to any cause; up to approximately 3 years] - OS is defined as the time from C1D1 to date of death due to any cause. * PK Parameter: Serum Concentrations of disitamab vedotin, total antibody, and unconjugated MMAE [Time Frame: From Cycle 1 Day 1 to end of treatment; up to approximately 2 years] - Antibody-drug conjugate, TAb, and u | — |
Countries
Japan, Puerto Rico, United States
Contacts
Public ContactClinical Trials Information Desk
Pfizer R&D Japan G.K.
Outcome results
None listed