159TiP TROPION-Breast04: Phase (ph) III study of neoadjuvant (neoadj) datopotamab deruxtecan (Dato-DXd) + durvalumab (D) followed by adjuvant (adj) D vs standard of care (SoC) in treatment-naïve, triple-negative (TN) and HR-low/HER2- breast cancer (BC)

SoC for patients (pts) with treatment-naïve, Stage II–III TNBC is neoadj pembrolizumab (pembro) + chemotherapy (CT) followed by surgery and adj pembro. However, there remains an unmet need to develop a treatment approach to improve pathological complete response (pCR) rates and long-term survival while reducing traditional CT-associated toxicity. Dato-DXd comprises a humanised, anti-TROP2 IgG1 monoclonal antibody conjugated to a potent topoisomerase I inhibitor via a plasma-stable, tetrapeptide-based, tumour-selective cleavable linker. Dato-DXd + D demonstrated durable responses in unresectable, advanced TNBC in the Ph Ib/II BEGONIA study. The ongoing Ph3 TROPION-Breast03 study is evaluating Dato-DXd ± D vs SoC as adj therapy in pts with Stage I–III TNBC and residual invasive disease at the time of surgery after neoadj treatment. TROPION-Breast04 (NCT06112379) aims to determine if outcomes can be improved with neoadj Dato-DXd + D followed by adj D vs SoC in treatment-naïve pts with early-stage TNBC or HR-low/HER2– BC. TROPION-Breast04 is a Ph3, 2-arm, parallel-group, randomised, open-label, multicentre study. ∼1728 pts (≥18 years) with previously untreated, Stage II–III, unilateral / bilateral, primary invasive TNBC or HR-low (ER and/or PR 1%–<10%; neither HR ≥10%)/HER2– BC and ECOG PS 0–1, will be randomised 1:1 into 1 of 2 arms (Table), stratified by lymph node status, tumour stage, HR status, and region. Primary endpoints: pCR and event-free survival. Secondary endpoints: overall survival, distant disease-free survival, patient-reported outcomes, pharmacokinetics, immunogenicity, safety/tolerability. Enrolment is planned in 26 countries/regions; recruitment is active in Canada, South Korea and Taiwan at the time of abstract submission.Table: 159TiPTROPION-Breast04 treatment armsTherapyNeoadjuvantSurgeryAdjuvantExperimental armDato-DXd[a + durvalumabb:8 cyclesIndicatedDurvalumabb:9 cycles ± olaparibc* chemotherapy†Control armdPembrolizumab + carboplatin + paclitaxel: 4 cycles followed by Pembrolizumab + cyclophosphamide + doxorubicin or epirubicin: 4 cyclesIndicatedDurvalumabb:9 cycles ± olaparibc* chemotherapy†*In combination with durvalumab/pembrolizumab in pts with gBRCA+ tumours and residual disease; not concurrently with chemo.†In combination with durvalumab/pembrolizumab in pts with residual disease. a6 mg/kg IV every 3 weeks (Q3W); b1120 mg IV Q3W; c300 mg orally twice daily for 1 year; dSoC doses. Open table in a new tab *In combination with durvalumab/pembrolizumab in pts with gBRCA+ tumours and residual disease; not concurrently with chemo.†In combination with durvalumab/pembrolizumab in pts with residual disease. a6 mg/kg IV every 3 weeks (Q3W); b1120 mg IV Q3W; c300 mg orally twice daily for 1 year; dSoC doses. NCT06112379. Medical writing support for the development of this abstract, under the direction of the authors, was provided by Werner Gerber of Ashfield MedComms (Fourways, South Africa), an Inizio company. AstraZeneca PLC in collaboration with Daiichi Sankyo. Pharmaceutical, biotech, or other commercial company; AstraZeneca PLC in collaboration with Daiichi Sankyo.