187P Stage I results of a phase II study of datopotamab deruxtecan (DATO-DXd) in triple-negative breast cancer (TNBC) patients (pts) with active brain metastases (TUXEDO-2)

• DOI: 10.1016/j.esmoop.2024.103209
• Publication Date: 2024-05-17T11:20:26Z
• Authors: R. Bartsch; A.S. Berghoff; J. Furtner; M. Marhold; A.M. Starzer; H. Forstner; B. Rottenmanner; B. Aretin; Z.A. Bago-Horvath; R. Exner; T. Fuereder; C. Minichsdorfer; M. Hirdler; K. Strasser-Weippl; M. Balic; G. Pfeiler; D. Egle; H. Rumpold; C.F. Singer; M. Preusser
• Keywords: Triple-negative breast cancer

Brain metastases (BM) are a common site of progression in TNBC increasing morbidity and mortality. Strategies providing both intra- extracranial disease control urgently required. Dato-DXd is Trop2-directed antibody-drug conjugate (ADC) with activity TNBC. Here we report results the first stage prospective single-arm phase II TUXEDO-2 trial investigating safety pts active BM. includes adult newly diagnosed untreated or progressing BM no indication for immediate local treatment. administered at dose 6.0 mg/kg once every 3 weeks. The primary endpoint intracranial response rate (RR) centrally assessed by Response Assessment Neuro-Oncology (RANO) criteria. Secondary endpoints consist RR, progression-free survival, overall safety, quality-of-life, neurocognitive function. Based on Simon's two-stage design (RR under alternative hypothesis >35%; RR null ≤11%), 8 patients were accrued stage. If ≥2 responses observed, will accrue an additional 12 pts. As February 7th, 2022, have been accrued; 75% had 25% progressive Two received prior sacituzumab govitecan one pt T-DXd as well. At data cut-off, 5 evaluable response. We observed objective responses, corresponding to 37.5%. One died from intestinal perforation (not related) progression, each before restaging; not yet All ADC-naïve Main toxicities consisted grade 1/2 fatigue. 2 stomatitis case interstitial lung was detected. With three positive, has progressed second Treatment generally well tolerated, new signals observed. may thus provide opportunity successful systemic therapy