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Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.088
vdae090.088
Final Category: Ongoing Clinical Trials
AcademicSubjects/MED00300
AcademicSubjects/MED00310
OCTS-03 A MULTICENTER, OPEN-LABEL, SINGLE-ARM, MULTICOHORT PHASE II CLINICAL TRIAL OF TRASTUZUMAB DERUXTECAN IN HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-POSITIVE AND HER2-LOW ADVANCED BREAST CANCER (ABC) WITH BRAIN METASTASES AND/OR LEPTOMENINGEAL CARCINOMATOSIS (LMC) – THE DEBBRAH STUDY
Vaz-Batista Marta Hospital Professor Doutor Fernando Fonseca EPE, Lisbon, Spain
Medica Scientia Innovation Research (MEDSIR) - Oncoclínicas&Co, Barcelona, Spain

Pérez-García José Manuel Medica Scientia Innovation Research (MEDSIR) - Oncoclínicas&Co, Barcelona, Spain
International Breast Cancer Center (IBCC), Pangaea Oncology, Quiron Group, Barcelona, Spain

Cortez Patricia IOB Institute of Oncology, Hospital Ruber Internacional, Quiron Group, Madrid, Spain

Garrigós Laia International Breast Cancer Center (IBCC), Pangaea Oncology, Quiron Group, Barcelona, Spain
Hospital Universitari Dexeus, Barcelona, Spain

Ruiz-Borrego Manuel Hospital Universitario Virgen del Rocío, Sevilla, Spain

de la Haba-Rodríguez Juan Instituto Maimonides de Investigacion Biomedica, Hospital Reina Sofia, Universidad de Córdoba, Córdoba, Spain

de las Heras Begoña Bermejo Hospital Clínico Universitario de Valencia, Valencia, Spain

Servitja Sonia Hospital del Mar, Barcelona, Spain

Racca Fabricio IOB Institute of Oncology, Quiron Group, Madrid and Barcelona, Spain

Fernández-Abad María Hospital Ramon y Cajal, Madrid, Spain
Universityo Alcalá de Henares, Madrid, Spain

Blanch Salvador Medica Scientia Innovation Research (MEDSIR) - Oncoclínicas&Co, Barcelona, Spain
Fundación Instituto Valenciano de Oncología, Valencia, Spain

Teurel Iris Instituto Catalán de Oncología de Badalona (ICO), Barcelona, Spain

Sáenz1 Jose Ángel Garcia Hospital Universitari Dexeus, Barcelona, Spain

Ortega Adela Fernandez Instituto Catalán de Oncología de Hospitalet de Llobregat (ICO), Barcelona, Spain

Martrat Griselda Medica Scientia Innovation Research (MEDSIR) - Oncoclínicas&Co, Barcelona, Spain

Shimizu Eileen Medica Scientia Innovation Research (MEDSIR) - Oncoclínicas&Co, Ridgewood, NJ, USA

Alcalá-López Daniel Medica Scientia Innovation Research (MEDSIR) - Oncoclínicas&Co, Barcelona, Spain

Pérez-Escuredo Jhudit Medica Scientia Innovation Research (MEDSIR) - Oncoclínicas&Co, Barcelona, Spain

Braga Sofia Hospital Professor Doutor Fernando Fonseca EPE, Lisbon, Spain

Llombart-Cussac Antonio Hospital Arnau de Vilanova; FISABIO, Valencia, Spain
Universidad Católica de Valencia, Valencia, Spain

Cortes Javier International Breast Cancer Center (IBCC), Pangaea Oncology, Quiron Group, Barcelona, Spain
Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain

Hospital Clínico San Carlos, Madrid, Spain
8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i26i27
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

The DEBBRAH study (NCT04420598) evaluated the efficacy and safety of trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate, in patients with HER2-positive and HER2-low ABC with brain metastases (BM) and/or LMC. Forty-one patients aged ≥18 years were enrolled in 5 cohorts: (1) HER2-positive ABC with non-progressing BM after radiotherapy and/or surgery (n=8); (2) HER2-positive or HER2-low ABC with asymptomatic untreated BM (n=10); (3) HER2-positive ABC with progressing BM after local treatment (n=9); (4) HER2-low ABC with progressing BM after local treatment (n=7); (5) HER2-positive or HER2-low ABC and pathologically confirmed LMC (n=7). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days until disease progression, unacceptable toxicity, or consent withdrawal. At the final analysis cut-off (4th April 2023), with a median follow-up of 15.2 months (range 2.1-30.1), three (7.3%) patients were still receiving T-DXd. In cohort 1, the 16-week progression-free survival rate was 87.5% (p<0.001), meeting the primary endpoint, with seven out of eight patients alive without progressive disease 16 weeks after initiating treatment, demonstrating intracranial and extracranial activity. Among cohorts 2, 3 and 4, intracranial overall response rates ranged from 50% to 70%. In cohort 5, the median overall survival rate was 13.3 months, meeting the primary endpoint. The most common hematologic treatment adverse events (TEAEs) (≥10%) were anemia (31.7%; 0% G≥3), neutropenia (24.4%; 9.8% G≥3) and thrombocytopenia (17.1%; 4.9% G≥3). Fatigue (60.9%; 4.9% G≥3) and nausea (52.2%; 2.4% G≥3) were the most common non-hematologic TEAEs. One (2.4%) patient died due to drug-related pneumonitis. In conclusion, T-DXd showed impressive activity and was consistent with the known safety profile in patients with HER2-positive and HER2-low ABC with a history of BMs and/or LMC. These results justify Destiny Breast 12 and reinforce the need to include this patient population in clinical trials evaluating HER2-targeted agents.
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pmc
