Abstract 335TiP
Background
HER2+ BC is associated with a high incidence (up to 50%) of brain metastasis (BM) despite advances in treatment (Freedman et al. J Clin Oncol. 2019). Although several agents have been studied in patients (pts) with HER2+ BC with BM, an unmet medical need remains due to the poor prognosis in this pt population. In DESTINY-Breast01, T-DXd demonstrated efficacy in the overall population and preliminary efficacy in a pt subgroup with stable BM, with a confirmed objective response rate (ORR) of 61.4% and an extracranial confirmed ORR by independent central review (ICR) of 58.3%, respectively, median progression-free survival (PFS) of 19.4 and 18.1 mo, respectively, and median duration of response (DOR) of 20.8 and 16.9 mo, respectively (Modi S et al. Cancer Res. 2021. Abst PD3-06; Jerusalem et al. Ann Oncol. 2020. Abst 138O). Here we describe a trial evaluating T-DXd in pts ± BM with previously treated advanced/metastatic HER2+ BC.
Trial design
DESTINY-Breast12 (NCT04739761) is an open-label, multicenter, international (86 sites in the US, Europe, Australia, and Japan), phase 3b/4 study assessing the efficacy and safety of T-DXd 5.4 mg/kg q3w in pts with HER2+ BC ± BM. Pts will be enrolled in 1 of 2 cohorts (250 pts each): cohort 1 (−BM at baseline) and cohort 2 (+BM at baseline). Pts must have previously treated advanced/metastatic HER2+ BC that has progressed with ≥1 prior anti-HER2–based regimen and received ≤2 lines of therapy in the metastatic setting (excludes pts with prior tucatinib). Pts with BM must have untreated BM not needing immediate local therapy or previously treated stable or progressing BM. Primary endpoints are ORR in cohort 1 and PFS in cohort 2 (both by RECIST version 1.1 per ICR). Secondary endpoints in both cohorts are OS, DOR, time to progression, duration of subsequent therapy, PFS2, safety, and changes in symptoms, functioning, and QOL. Incidence of new symptomatic CNS metastasis (CNSM) is a secondary endpoint in cohort 1, and ORR and CNS ORR by RECIST 1.1 per ICR, CNS PFS and DOR, and time to new CNSM are secondary endpoints in cohort 2.
Clinical trial identification
NCT04739761.
Editorial acknowledgement
Medical editorial assistance was provided by ArticulateScience LLC, and funded by AstraZeneca Pharmaceuticals LP.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
N.U. Lin: Financial Interests, Institutional, Other, All support for the present manuscript/abstract (e.g., funding, provision of study materials, medical writing, article processing charges, etc.): AstraZeneca; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Zion Pharmaceuticals; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Role: Prelude Therapeutics; Financial Interests, Personal, Advisory Role: Denali Therapeutics; Financial Interests, Personal, Advisory Role: Olema Pharma; Financial Interests, Personal, Advisory Role: Aleta Bio. E. Ciruelos: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Role: Celgene. G. Jerusalem: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Lilly; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MedImmune; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: AbbVie; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Pfizer. V. Müller: Non-Financial Interests, Personal, Other, Writing support: AstraZeneca; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Seagen; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Personal, Advisory Role: Genomic Health; Financial Interests, Personal, Advisory Role: Hexal; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: ClinSol; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Tesaro; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Nektar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Teva; Financial Interests, Personal, Invited Speaker: Seattle Genetics; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche; Financial Interests, Personal, Invited Speaker, Support for attending meetings and/or travel: Pfizer; Financial Interests, Personal, Invited Speaker, Support for attending meetings and/or travel: Daiichi Sankyo; Financial Interests, Institutional, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Novartis; Financial Interests, Institutional, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Roche; Financial Interests, Institutional, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Seagen; Financial Interests, Institutional, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Genentech. N. Niikura: Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Kyowa-Kirin; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Nippon; Financial Interests, Personal, Invited Speaker: Mediphysics; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Tiho; Financial Interests, Personal, Invited Speaker: Nippon Kayaku; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MSD. G. Viale: Financial Interests, Institutional, Research Grant: Ventana; Financial Interests, Institutional, Research Grant: Cepheid; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Advisory Role: Dako/Agilent; Financial Interests, Personal, Advisory Role: Menarini; Financial Interests, Personal, Advisory Role: Medscape; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche/Genentech; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Daiichi Sankyo; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Pfizer; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Ventana; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Novartis; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Roche; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: MSD Oncology; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca. E. Oscroft, S. Anand: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. G. Walker: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca. N. Harbeck: Financial Interests, Institutional, Other, All support for the abstract: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: SeaGen; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Lilly; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: MSD; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Pierre Fabre; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Pfizer; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: SeaGen; Financial Interests, Personal, Other, Co-Director: WSG.