Abstract 330TiP
Background
In the DESTINY-Breast01 study, T-DXd demonstrated a strong efficacy in HER2+ MBC patients (pts) with and without asymptomatic central nervous system (CNS) metastases. T-DXd has also showed promising antitumor activity in HER2-LE (IHC 1+ or 2+ and lack of HER2 amplification) MBC. DEBBRAH is assessing the efficacy and safety of T-DXd in HER2+ and HER2-LE MBC pts with BM and/or LMC.
Trial design
This is an open-label, single-arm, multicenter, phase 2 study. A total of 39 pts will be assigned to one of the following 5 cohorts: (1) HER2+ MBC with non-progressing BM after radiotherapy and/or surgery (N=8); (2) HER2+ or HER2-LE MBC with asymptomatic untreated BM (N=10); (3) HER2+ MBC with progressing BM after local treatment (N=7); (4) HER2-LE MBC with progressing BM after local treatment (N=7); (5) HER2+ or HER2-LE MBC with LMC (N=7). Main selection criteria include: (a) Pts age ≥18 years with pretreated HER2+ or HER2-LE MBC with stable, progressing, or untreated BM and/or LMC; (b) Cohorts 2–4: measurable brain disease; (c) For HER2+ MBC pts: previous treatment with a taxane and ≥1 HER2-targeted therapy for MBC; (d) For HER2-LE MBC pts who are hormone receptor (HR)-negative: previous treatment with ≥1 chemotherapy regimen for MBC. If HR+: previous treatment with ≥1 chemotherapy and 1 endocrine regimen for MBC. Pts will receive 5.4 mg/kg T-DXd intravenously on day 1 of a 21-day cycle until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint for cohort 1 is 16-week progression-free survival as per RANO-BM for CNS lesions and RECIST v.1.1 for extracranial lesions; for cohorts 2–4, CNS overall response rate; for cohort 5, overall survival. Secondary endpoints: additional efficacy outcome and safety as per CTCAE v.5.0. Exploratory endpoints: patient-reported outcomes and predictive or prognostic biomarkers. A single-arm binomial design is used for cohorts 1–4 and a time-to-event design for cohort 5. A futility interim analysis has been planned in cohort 1 after accrual of 4 pts. Sample size was planned to attain an 80% power at nominal level of one-sided α of 0.05 in each cohort.
Clinical trial identification
NCT04420598.
Editorial acknowledgement
Legal entity responsible for the study
MedSIR.
Funding
AZ/Daiichi Sankyo.
Disclosure
M. Vaz Batista: Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Daiichi Sankyo. J.M. Pérez-Garcia: Financial Interests, Personal, Advisory Role: Roche, Lilly, Daiichi Sankyo; Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche. A. Llombart Cussac: Financial Interests, Personal, Project Lead: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, MSD; Financial Interests, Personal, Stocks/Shares: MedSIR, Initia-Research; Financial Interests, Personal, Advisory Role: Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, GenomicHealth, GSK; Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, MSD; Financial Interests, Institutional, Research Grant: Roche, Foundation Medicine, Pierre-Fabre, Agendia; Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Lilly, Novartis, Pfizer, AstraZeneca. M. Ruiz Borrego: Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi Sankyo. F. Racca: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Roche, Bristol Myers Squibb; Financial Interests, Personal, Expert Testimony: Pharmore Research, Psyma; Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Merck Sharp & Dohme, Bristol Myers Squibb. S. Servitja: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, AstraZeneca, MSD, Genomic health; Financial Interests, Personal, Speaker’s Bureau: Roche, MSD, Eisai. L. Lema: Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer. M. Galàn Garmaje: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly, Novartis, Pierre-Fabre, Roche, Bristol Myers Squibb; Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis, Roche, Bristol Myers Squibb. S. González-Santiago: Financial Interests, Personal, Advisory Role: GSK, MSD, Roche, Pfizer. M. Gion: Financial Interests, Personal, Other, honoraria: Roche; Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer. J. Cortés: Financial Interests, Personal, Advisory Role: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology; Financial Interests, Personal, Other, honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F. Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London.; Financial Interests, Personal, Stocks/Shares: MedSIR. S. Braga: Non-Financial Interests, Personal, Other, Travelling, hotel and meal expenses: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Other, honoraria: Daiichi Sankyo. All other authors have declared no conflicts of interest.