Abstract 261TiP
Background
Standard of care for pts with metastatic PD-L1+ (Combined Positive Score [CPS] ≥10) TNBC is pembro + CT, but prognosis remains poor. Dato-DXd comprises a humanised, anti-TROP2 IgG1 mAb conjugated to a potent topoisomerase I (Topo-I) inhibitor via a plasma-stable, tetrapeptide-based, tumour-selective cleavable linker. D is a high-affinity, human IgG1 mAb that blocks interaction of PD-L1 with PD-1 and CD80 by binding to PD-L1. In the Ph1 TROPION-PanTumor01 study, Dato-DXd demonstrated a manageable safety profile and encouraging efficacy in heavily pretreated metastatic TNBC. In the PhIb/2 BEGONIA study, Dato-DXd + D showed durable responses in unresectable advanced TNBC. TROPION-Breast05 (NCT06103864) will evaluate Dato-DXd ± D vs investigator’s choice of CT (ICC) + pembro in PD-L1+ locally recurrent inoperable or metastatic TNBC.
Trial design
The Ph3, randomized, open-label, 3-arm, multicentre TROPION-Breast05 study will randomise ∼625 pts (≥18 years) with histologically/cytologically documented, locally recurrent inoperable or metastatic PD-L1+ (CPS ≥10) TNBC not previously treated with CT or targeted systemic anticancer therapy. Pts with active brain metastases, or prior exposure to Topo-I ADC or TROP2-targeted therapy will be excluded. Pts will be randomised 1:1 to Arm 1 (Dato-DXd 6 mg/kg IV every 3 weeks [Q3W] + D 1120 mg IV Q3W) or Arm 2 (ICC [paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin] + pembro), or in selected countries, 1:1:1 to Arms 1, 2, or 3 (Dato-DXd alone). Once ∼75 pts have been randomised to Arm 3, it will close and all countries will continue with 1:1 randomisation. Primary endpoint: progression-free survival (PFS) by blinded independent central review per RECIST v1.1. Secondary endpoints: overall survival, objective response rate, duration of response, investigator-assessed PFS, PFS2, clinical benefit rate at 24 weeks, patient-reported outcomes, pharmacokinetics, immunogenicity, safety. Enrolment is planned in 20 countries/regions; recruitment is active in the UK, South Korea and Taiwan at the time of abstract submission.
Clinical trial identification
NCT06103864.
Editorial acknowledgement
Medical writing support for the development of this abstract, under the direction of the authors, was provided by Helen Kitchen of Ashfield MedComms (Macclesfield, UK), 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
P. Schmid: Financial Interests. PROVIDENCE: A prospective, non-interventional study examining real-world clinical and patient-reported outcome (PRO) data in patients (pts) with HER2-positive or HER2-low unresectable or metastatic breast cancer (mBC) treated with trastuzumab deruxtecan, 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. M. Oliveira: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo / AstraZeneca, Gilead, Lilly, MSD, Relay Therapeutics, Roche, Seagen, Cureo Science, iOne, Pfizer; Financial Interests, Personal, Invited Speaker: Eisai, Gilead, Pfizer, Roche, Seagen, AstraZeneca, Lilly, Medscape, AstraZeneca, AstraZeneca; Financial Interests, Personal, Other, Educational activity: Libbs; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer-Ingelheim, GSK, Roche, Seattle Genetics, Zenith Epigenetics, Gilead, Ayala Pharmaceuticals, Pfizer; Financial Interests, Invited Speaker: Roche; Non-Financial Interests, Member of Board of Directors, Head: SOLTI Breast Cancer Research; Other, Travel Grant: Pierre Fabre, Eisai, Gilead, AstraZeneca. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie, Agendia, Amgen, Aptitude Health, AstraZeneca, Bristol Myers Squibb, Celgene, Eisai, G1 Therapeutics, Genentech, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Novartis, Ondonate, Pfizer, Puma, Prime Oncology, Roche, Seattle Genetics, Syndax, Carrick Therapeutics, Daiichi Sankyo, Gilead Sciences, Ontada, Pierre Fabre Pharmaceuticals, Samsung Bioepis, Sanofi. M. Cristofanilli: Financial Interests, Personal, Other, Travel support: Foundation Medicine; Financial Interests, Personal, Advisory Board, DSMB/Advisory Board: Merck and AstraZeneca; Financial Interests, Institutional, Funding, Research funding: Pfizer Inc., Menarini, Eli Lilly, and G1 Therapuetics; Financial Interests, Personal, Advisory Role, Consulting/Lecture fees: Novartis, Menarini, Eli Lilly, Sermonix, G1 Therapeutics, Foundation Medicine, AstraZeneca, Foundation Medicine, and Pfizer Inc. S.L. Graff: Financial Interests, Personal, Advisory Board: Pfizer, Seagen, Novartis, AstraZeneca, Genentech, Lilly, Gilead Sciences, Daiichi Sankyo, Menarini; Financial Interests, Personal, Invited Speaker: The Academy for Healthcare Learning, DAVA Oncology, MJH Life Sciences, MedPage Today, MedIQ, Medical Educator Consortium; Financial Interests, Personal, Stocks/Shares: HCA Healthcare. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Invited Speaker, Clinical Trial Budget: AstraZeneca, Eisai, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. S. Loi: Financial Interests, Institutional, Expert Testimony, Consultant: Aduro Biotech, Pfizer, Seattle Genetics; Financial Interests, Institutional, Advisory Board, Consultant: Novartis, GSK, Roche Genentech, AstraZeneca, Silverback Therapeutics, G1 Therapeutics; Financial Interests, Institutional, Expert Testimony, COnsultant: PUMA Biotechnologies, BMS; Financial Interests, Institutional, Expert Testimony, consultant: Gilead Therapeutics, Daiichi Sankyo, Merck, Amunix, Tallac Therapeutics, Eli Lilly; Financial Interests, Institutional, Funding, Research: Novartis, BMS, Merck, PUMA Biotechnology, Eli Lilly, Nektar Therapeutics, AstraZeneca, Seattle Genetics, Roche - Genentech; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Seattle Genetics, Novartis, Bristol Myers Squibb, Merck, AstraZeneca, Roche Genentech; Non-Financial Interests, Advisory Role, consultant (not compensated): Eli Lilly, Pfizer, Gilead Therapeutics. S. Saji: Financial Interests, Personal, Invited Speaker: Eli Lilly, Chugai, AstraZeneca, Kyowa Kirin, Daiichi Sankyo, Taiho, Pfizer, MSD, Novartis, Eisai, Ono, Takeda, Exact Sciences; Financial Interests, Institutional, Research Grant: Taiho, Chugai, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: MSD, Daiichi Sankyo, Chugai, AstraZeneca, Sanofi; Non-Financial Interests, Member of Board of Directors: Japanese Breast Cancer Society, Japanse Society of Medical Oncology, Japan Breast Cancer Research Group, Breast International Group. S. Wang: Financial Interests, Personal, Invited Speaker: Pfizer, Roche, AstraZeneca, NORVATS; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer, AstraZeneca, Roche; Financial Interests, Personal and Institutional, Research Grant: Pfizer. D.W. Cescon: Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, GSK, Inflex, Inivata/NeoGenomics, Lilly, Merck, Novartis, Pfizer, Roche and Saga.; Financial Interests, Institutional, Funding: AstraZeneca, Guardant Health, Gilead, GSK, Inivata/NeoGenomics, Knight, Merck, Pfizer, ProteinQure and Roche.; Financial Interests, Personal, Royalties: Patent: US62/675, 228, for methods of treating cancers characterized by a high expression level of spindle and kinetochore associated complex subunit 3 (ska3) gene. T. Hovey: Financial Interests, Institutional, Invited Speaker: AstraZeneca. A. Nawrot: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. K. Tse: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. P. Vukovic: Financial Interests, Personal and Institutional, Full or part-time Employment: AstraZeneca; Financial Interests, Personal and Institutional, Stocks/Shares: AstraZeneca. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Advisory Board, Advisory Board: Menarini, Gilead; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Member of Board of Directors, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Officer, ESMO Clinical Practice Guidelines Chair: ESMO; Non-Financial Interests, Member of Board of Directors, Chair of Clinical Practice Guidelines Committee: ESMO.