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)

Background

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.

Trial design

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: 159TiP

TROPION-Breast04 treatment arms

*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.

Clinical trial identification

NCT06112379.

Editorial acknowledgement

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.

Legal entity responsible for the study

AstraZeneca PLC in collaboration with Daiichi Sankyo.

Funding

Pharmaceutical, biotech, or other commercial company; AstraZeneca PLC in collaboration with Daiichi Sankyo.

Disclosure

S. Loibl: Financial Interests, Institutional, Advisory Board, Member: Amgen, AstraZeneca, BMS, Celgene, EirGenix, GSK, Lilly, Pierre Fabre, Roche, Seagen, AbbVie, Sanofi, Gilead, Merck, Novartis, Relay Therapeutics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, DSI, Novartis, Pfizer, Roche, Gilead, Seagen, Stemline-Menarini; Financial Interests, Institutional, Advisory Board: DSI, Pfizer, Olema; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Invited Speaker, Ki67 Quantifier: VMscope GmbH; Financial Interests, Institutional, Research Grant: AstraZeneca, Celgene, Novartis, Immunomedics/Gilead, Pfizer, Roche, Daiichi Sankyo; Financial Interests, Institutional, Funding: AbbVie, Molecular Health, Greenwich Life Sciences; Financial Interests, Personal, Other, PIPenelope/Padma: Pfizer; Financial Interests, Personal, Other, SC PALOMA3: Pfizer; Financial Interests, Personal, Other, SC SOLAR1: Novartis; Financial Interests, Personal, Other, SC ASCENT: Immunomedics/Gilead; Financial Interests, Personal, Other, SC HERCLIMB: Seagen; Financial Interests, Personal, Other, SC Katherine: Roche; Financial Interests, Personal, Other, SC Capitello; EC Cambria 1: AstraZeneca; Financial Interests, Personal, Other, SC Inavo: Roche; Financial Interests, Personal, Other, SC Destiny B05; SC Destiny B09: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, After publication of primary endpoint: PI Aphinity; Non-Financial Interests, Advisory Role, Group in Germany responsible for breast cancer guidelines: AGO Kommission Mamma; Non-Financial Interests, Member, German Gynaecological Oncology society: AGO; Non-Financial Interests, Member, German Cancer Society: DKG; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member, Member guideline committee; past chair in ESMO Breast: ESMO; Other, EP14153692.0No financial interest, Institutional: Patent; Other, EP21152186.9No financial interest, institutional: Patent; Other, EP19808852.8 No financial interest, Institutional: Patent. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad board participant/consultant: ARC Therapeutics, Daiichi Sankyo, Eisai, Genentech/Roche, Gilead, Novartis, Sanofi, Seagen; Financial Interests, Personal, Other, Consulting: Aadi BioPharma; Financial Interests, Personal, Advisory Board, Ad board participation: Artios, Incyte Corp, BeyondSprings; Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Advisory Board participation: Bayer, Infinity Therapeutics, Myovant, OncXerna, Umoja Biopharma, Zentalis, Zetagen, Natera; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, Mersana Therapeutics; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory board/consulting: Jazz Pharma; Financial Interests, Institutional, Funding, And steering committing: AstraZeneca; Financial Interests, Institutional, Funding, And steering committee: Eli Lilly; Financial Interests, Institutional, Funding: Pfizer, Sanofi, Seagen, Odonate, Cyclacel, Exelixis, Bristol Myers Squibb, Eisai, Merck, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: CytomX; Financial Interests, Institutional, Funding, and steering committee: Gilead, Genentech/Roche; Financial Interests, Institutional, Invited Speaker: Stemline/Menarini. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Gilead, Eisai, MSD, Seagen, Amgen, Celgene, Lilly; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation. B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca, Seagen, Lilly, Daiichi Sankyo, MSD; Financial Interests, Institutional, Invited Speaker: Gilead, Novartis, AstraZeneca, AstraZeneca, Gilead, Seagen, MSD, Novartis, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, travel support: AstraZeneca, Pierre Fabre, MSD, Daiichi Sankyo; Financial Interests, Personal, Other, Travel support: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Project Lead: Unicancer. R.A. Dent: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Pfizer, Merck, Lilly, Eisai; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Pfizer, Merck, Lilly, AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker: Roche; Financial Interests, Personal and Institutional, Research Grant, Investigator Initiated Trial: AstraZeneca. Q. Liu: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Pfizer, Eisai, Novartis; Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Pfizer, Eisai, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer; Financial Interests, Personal, Funding: Eisai. J.L. Meisel: Financial Interests, Personal, Invited Speaker: Prime Oncology, Targeted Oncology; Financial Interests, Personal, Advisory Board: Sermonix; Financial Interests, Institutional, Invited Speaker: Olema, Sermonix, Seagen (now Pfizer); Financial Interests, Personal, Advisory Role: Pfizer, Novartis, Puma, Seagen (now Pfizer), Olema, Genentech, GSK, AstraZeneca, Sermonix. N. Niikura: Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Daiichi Sankyo, Chugai, Eli Lilly, MSD; Financial Interests, Personal and Institutional, Research Grant: Chugai, Eisai, Nippon Kayaku; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Roche, Novartis, MSD, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Roche, Novartis, MSD, Daiichi Sankyo; Financial Interests, Institutional, Other, Research Grant: AstraZeneca, Pfizer, Roche, MSD; Financial Interests, Institutional, Invited Speaker: Pfizer; Non-Financial Interests, Principal Investigator: AstraZeneca, Pfizer, Novartis, MSD, Lilly, Roche, Daiichi Sankyo. G. Werutsky: Financial Interests, Personal, Advisory Board: Organon, Novartis; Financial Interests, Personal, Invited Speaker: MSD, Roche, Pfizer, AstraZeneca; Financial Interests, Institutional, Research Grant: Novartis, Roche, Pfizer, Astellas, Janssen, Takeda, AstraZeneca, Ipsen; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Lilly, BMS, MSD; Financial Interests, Personal and Institutional, Invited Speaker: Novartis, Roche. G. Bianchini: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Lilly, Novartis, Pfizer, Roche, Amgen, MSD, Chugai, Eisai, Gilead, Seagen, Exact Science, Roche, MSD, Gilead; Financial Interests, Personal, Other, Consultancy: AstraZeneca, Daiichi Sankyo, Roche, MSD, Gilead, Sanofi; Financial Interests, Personal, Invited Speaker: Lilly, Roche, AstraZeneca, Daiichi Sankyo, MSD, Chugai, Eisai, Gilead, Seagen, Neopharm Israel; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche, Pfizer, MSD, Chugai, Novartis, Gilead, Daiichi Sankyo; Financial Interests, Personal and Institutional, Invited Speaker: Roche, Novartis, Lilly, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Gilead, Pfizer, Daiichi Sankyo, Lilly, MSD, Novartis; Non-Financial Interests, Leadership Role, Head of Traslational Research: Fondazione Michelangelo. J.C. Andersen: Financial Interests, Personal, Invited Speaker, speaker's bureau: AstraZeneca, Diacchi Sankyo, Exact Sciences, Immunomedics, Seattle Genetics, Puma; Financial Interests, Personal, Advisory Board, one time ad board meeting: Merck, Biotheranostics, AstraZeneca; Financial Interests, Personal, Invited Speaker, I received payment for my research time: Pierre Fabre, Merck; Financial Interests, Institutional, Invited Speaker, payments to my institution to cover the cost of research: Merck, Genentech, Immunomedics, Greenwich Life Sciences. N. Rokutanda: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. H.L. McArthur: Financial Interests, Personal, Advisory Board: Lilly, Pfizer, Immunomedics, Merck, Seattle Genetics, Daiichi Sankyo, Bristol Myers Squibb, AstraZeneca, Puma Biotechnology, Gilead, Crown Bioscience, Roche, Novartis, Genentech; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, MedImmune, AstraZeneca, Merck. All other authors have declared no conflicts of interest.