Abstract 187P
Background
Brain metastases (BM) are a common site of progression in TNBC increasing morbidity and mortality. Strategies providing both intra- and extracranial disease control are urgently required. Dato-DXd is a Trop2-directed antibody-drug conjugate (ADC) with activity in TNBC. Here we report results of the first stage of the prospective single-arm phase II TUXEDO-2 trial investigating activity and safety of Dato-DXd in TNBC pts with active BM.
Methods
TUXEDO-2 includes adult TNBC pts with newly diagnosed untreated or progressing BM and no indication for immediate local treatment. Dato-DXd is administered at a dose of 6.0 mg/kg once every 3 weeks. The primary endpoint is intracranial response rate (RR) centrally assessed by Response Assessment in Neuro-Oncology (RANO) BM criteria. Secondary endpoints consist of extracranial RR, progression-free survival, overall survival, safety, quality-of-life, and neurocognitive function. Based on a Simon’s two-stage design (RR under alternative hypothesis >35%; RR under null hypothesis ≤11%), 8 patients were accrued in the first stage. If ≥2 responses are observed, the trial will accrue an additional 12 pts.
Results
As of February 7th, 2022, 8 pts have been accrued; 75% had newly diagnosed BM and 25% progressive BM. Two pts had received prior sacituzumab govitecan and one pt prior T-DXd as well. At the data cut-off, 5 pts were evaluable for response. We observed 3 objective intracranial responses, corresponding to a RR of 37.5%. One pt died from intestinal perforation (not related) and one pt died from extracranial disease progression, each before the first restaging; one pt is not yet evaluable for response. All responses were observed in ADC-naïve pts. Main toxicities consisted of grade 1/2 fatigue. One pt had grade 2 stomatitis and one case of grade 3 interstitial lung disease was detected.
Conclusions
With three intracranial responses, the first stage of TUXEDO-2 is positive, and the trial has progressed to the second stage. Treatment was generally well tolerated, and no new safety signals were observed. Dato-DXd may thus provide an opportunity for successful systemic therapy of active BM in TNBC.
Clinical trial identification
NCT05866432.
Legal entity responsible for the study
Medical University of Vienna.
Funding
Daiichi Sankyo.
Disclosure
R. Bartsch: Financial Interests, Personal, Invited Speaker: AstraZeneca, Seagen, Roche, Novartis, Eli Lilly, Pierre-Fabre, Daiichi, Gilead, MSD, Pfizer, Eisai, Gruenenthal; Financial Interests, Personal, Advisory Board: Daiichi, AstraZeneca, Roche, Novartis, Eli Lilly, Pierre-Fabre, MSD, Gilead, Seagen, Eisai, Gruenenthal, Menarini; Financial Interests, Institutional, Funding, Investigator Initiated Trial: Daiichi; Financial Interests, Institutional, Invited Speaker, Drug support for investigator initiated trial: MSD. A.S. Berghoff: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Advisory Board: BMS, Merck, DSI, AstraZeneca, CeCaVa, Seagen, Alexion, Servier; Financial Interests, Other, Travel Suppport: Roche, Amgen, AbbVie. J. Furtner: Financial Interests, Personal, Invited Speaker: Seagen, Novartis, Sanova; Financial Interests, Personal, Advisory Board: Servier. M. Marhold: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Advisory Board: Gilead, Eli Lilly, Novartis, AstraZeneca, Daiichi, Pfizer, MedMedia; Financial Interests, Other, Travel Support: Amgen, Gilead, Roche, Novartis, Pierre Fabre, MSD, Daiichi, Eisai. A.M. Starzer: Financial Interests, Personal, Invited Speaker, Lecture honoraria: AstraZeneca; Financial Interests, Institutional, Research Grant, Industry partner of institutional Christian Doppler Laboratory: Roche; Non-Financial Interests, Member, National Oncology Society: OeGHO; Non-Financial Interests, Member, Oncology society of USA: ASCO; Other, Travel support for conference participation: MSD, Lilly. Z.A. Bago-Horvath: Financial Interests, Personal, Advisory Board, Advisory Board Trastuzumab Deruxtecan: AstraZeneca, Daiichi Sankyo Sanyo; Financial Interests, Personal, Advisory Board, Advisory Board Sacituzumab Govitecan: Gilead; Financial Interests, Personal, Other, Travel support: Roche; Financial Interests, Personal, Invited Speaker, Speaker at CME Lectures: MSD; Non-Financial Interests, Institutional, Product Samples, Reagents: Roche. T. Fuereder: Financial Interests, Advisory Board: MSD, BMS, AstraZeneca, Roche, Sanofi, Merck, Boehringer Ingelheim, Janssen, Eli Lilly, Invios, Takeda, Amgen, GSK, Pfizer; Financial Interests, Institutional, Research Grant: Merck, MSD. C. Minichsdorfer: Financial Interests, Advisory Board: MSD, Boehringer Ingelheim, Merck, Amgen; Financial Interests, Invited Speaker: Sandoz; Financial Interests, Other, Travel Support: MSD, Merck. K. Strasser-Weippl: Financial Interests, Advisory Board: Roche, Pfizer, Novartis, Eli Lilly, Daiichi, Myriad, Seagen, MSD, AstraZeneca, Gilead, GSK; Financial Interests, Other, Travel Support: Roche, Pfizer, MSD, Novartis. M. Balic: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Daiichi Sankyo, MSD, Pierre Fabre, Pfizer, Roche, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eli Lilly, Eli Lilly, MSD, Novartis, Novartis, Pierre Fabre, Pfizer, Roche, Gilead; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker, Steering Committee Member, Coordinating PI, Advisory role: Roche; Financial Interests, Institutional, Invited Speaker: Roche, Austrian Breast and Colorectal Cancer Study Group, MSD, Qiagen, Amgen, Pierre Fabre, Novartis, Pfizer, Gilead. G. Pfeiler: Financial Interests, Advisory Board: Pfizer, Daiichi, MSD, Stemline, Merck, Roche, Eli Lilly, Novartis, AstraZeneca, Gilead, Accord. D. Egle: Financial Interests, Personal, Advisory Board: AstraZeneca, Gilead, Pfizer, Novartis, Lilly, Seagen, Pierre-Fabre, MSD; Financial Interests, Personal, Invited Speaker: Roche, Sirius Medical; Financial Interests, Personal, Expert Testimony: Daiichi Sankyo. H. Rumpold: Financial Interests, Invited Speaker: Daiichi. C.F. Singer: Financial Interests, Personal, Other, consultancy: Amgen; Financial Interests, Personal, Advisory Board, Advisory Function: Novartis; Financial Interests, Personal, Advisory Board, advisory role: Roche; Financial Interests, Personal, Other, Study Support: Pfizer; Financial Interests, Personal, Advisory Board, Advisory, Speaker Honoraries, Study Support: AstraZeneca; Financial Interests, Personal, Invited Speaker, Study Coordinator: Amgen; Non-Financial Interests, Principal Investigator, STUDY: Amgen, AstraZeneca; Non-Financial Interests, Project Lead, register: Pfizer. M. Preusser: Financial Interests, Advisory Board: Bayer, BMS, Novartis, GSK, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Eli Lilly, Daiichi, MSD, Tocagen, Adastra, Gan & Lee Pharmaceutical. All other authors have declared no conflicts of interest.