Abstract 274TiP
Background
Chemotherapy is the main treatment in patients (pts) with pretreated endocrine-resistant HR+/HER2– metastatic breast cancer (BC), but has limited efficacy and substantial toxicities. The antibody-drug conjugate Dato-DXd consists of a humanized IgG1 mAb targeting TROP2 attached via a stable cleavable linker to a topoisomerase I (TopI) inhibitor payload. The TROPION-PanTumor01 (NCT03401385) study of Dato-DXd in heavily pretreated, metastatic, triple-negative BC showed a manageable safety profile and highly encouraging objective response rates (ORR by blinded independent central review [BICR]: 34% in all pts; 52% in pts treatment-naïve to TopI inhibitor-based therapies). The metastatic HR+/HER2– BC cohort of TROPION-PanTumor01 has completed enrolment (n=41); data are currently maturing.
Trial design
TROPION-Breast01 (NCT05104866) is an ongoing, global, phase III, open-label, randomized trial evaluating efficacy and safety of Dato-DXd vs ICC in pts with inoperable or metastatic HR+/HER2– BC. Pts (n≈700) are randomized 1:1 to Dato-DXd 6 mg/kg IV Q3W or ICC (eribulin, capecitabine, vinorelbine, or gemcitabine) until progression. Adults with ECOG PS 0–1, who experienced progression on or are unsuitable for endocrine therapy, and received 1–2 prior lines of standard-of-care chemotherapy in the inoperable or metastatic setting are eligible. Inhibitors of mTOR, PD-[L]1, CDK4/6 and PARP do not count as prior chemotherapy lines. Pts must have ≥1 measurable lesion per RECIST 1.1 and an archival or fresh FFPE tumour sample. Clinically inactive brain metastases are permitted. Dual primary endpoints are progression-free survival (PFS) by BICR, and overall survival. Secondary endpoints include PFS per investigator, ORR, disease control rate, pt-reported outcomes, and Dato-DXd pharmacokinetics and immunogenicity. Exploratory endpoints include TROP2 expression and exposure–efficacy relationship. Pts are stratified by number of prior chemotherapy lines, prior CDK4/6 inhibitor use, and region. Enrolment is ongoing.
Clinical trial identification
NCT05104866.
Editorial acknowledgement
Medical writing support for the development of this abstract, under the direction of the authors, was provided by Catherine Crookes of Ashfield MedComms (Macclesfield, UK), an Ashfield Health company, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca PLC in collaboration with Daichii Sankyo.
Funding
AstraZeneca in collaboration with Daichii Sankyo.
Disclosure
A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics/Gilead, Sanofi, Daiichi Pharma, AstraZeneca, Phillips, Eli Lilly, Foundation medicine; Financial Interests, Personal, Research Grant: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daichii Pharma, AstraZeneca, Eli Lilly. K. Kalinsky: Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, Eisai, AstraZeneca, Daichii-Sankyo, Puma, 4D Pharma, Oncosec, Immunomedics, Merck, Seattle Genetics, Cyclocel, Pfizer; Financial Interests, Personal, Full or part-time Employment, spouse: Grail, Array Biopharma; Financial Interests, Personal, Full or part-time Employment, spouse (formerly employed): Pfizer. J. Tsurutani: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, AstraZeneca, Eisai; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca, Eisai; Financial Interests, Institutional, Research Grant: Daichii Sankyo, Eisai, FSJD, WJOG; Financial Interests, Personal, Principal Investigator: Daiichi Sankyo, Eisai, Seagen, Taiho, Eli Lilly, MSD, Oncotherapy; Financial Interests, Personal, Expert Testimony, Drug Price decision at PMDA: Daiichi Sankyo. E.P. Hamilton: Financial Interests, Institutional, Research Grant: AstraZeneca/MedImmune, Hutchinson MediPharma, OncoMed, Stem CentRx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Mersana, Millennium, TapImmune, Lilly, Pfizer, Tesaro, BI, H3 Biomedicine, Radius Health, Acerta Pharma, Macrogenics, Abbvie, Immunomedics, Fujifilm, eFFECTOR Therapeutics, Merus, Nucana, Regeneron, Leap Therapeutics, Taiho Pharmaceutical, EMD Serono, Daiichi Sankyo, ArQule, Syros Pharmaceutical, Clovis Oncology, Cytomx Therapeutics, InvestisBio, Deciphera, Sermonix Pharmaceutical, Sutro Biopharma, Zenith Epigenetics, Arvinas, Harpoon, Fochon Pharmaceutical, Black Diamond Therapeutics, Orinove, Molecular Templates, Silverback Therapeutics, SeaGen, Compugen, G1 Therapeutics, Karyopharm Therapeutics, Dana Farber Cancer Institute, Onconova Therapeutics, Shattuck Labs, Merck, PharmaMar, Olema Pharmaceutical, Immunogen, Plexxikon, Amgen, Akesobio, ADC Therapeutics, AtlasMedx, Aravive, Ellipses Pharma, Incyte, MabSpace Biosciences, Myriad Genetics, ORIC Pharmaceutical, Pieris Pharmaceutical, Pionyr, Repertoire Immune Medicines, Treadwell Therapeutics, Vincerx Pharma, Jacobio; Financial Interests, Personal, Advisory Board: Pfizer, Roche/Genentech, Lilly, Puma, Daichii Sankyo, Mersana, BI, AstraZeneca, Novartis, Silverback Therapeutics, Black Diamon, Cytomx Therapeutics, Dantari, H3 Biomedicine, Merck, SeaGen, Eisai, Deciphera, Arvinas, Arcus Biosciences, iTeos Therapeutics, Janssen, Loxo, Relay Therapeutics. S. Johnston: Financial Interests, Personal, Speaker’s Bureau: Pfizer, AstraZeneca, Roche/Genentech; Financial Interests, Personal, Advisory Board: Eli Lilly, AstraZeneca, Puma Biotechnology, Pfizer, Novartis, Sanofi Genzyme; Financial Interests, Institutional, Research Grant: Pfizer, Puma Biotechnology, Eli Lilly, Pfizer, AstraZeneca, Novartis, Roche/Genentech; Financial Interests, Personal, Advisory Role: Eli Lilly, AstraZeneca, Puma Biotechnology, Pfizer, Novartis, Sanofi Genzyme. J. Sohn: Financial Interests, Institutional, Research Grant: MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GSK, Daiichi Sankyo, Sanofi, BI. Y.H. Park: Non-Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly, Daiichi Sankyo, Pfizer, Novartis, Roche, Merck Sharp & Dohme; Non-Financial Interests, Personal, Writing Engagements: Roche, Pfizer, Daiichi Sankyo, Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Daiichi Sankyo, Pfizer, Novartis, Roche, Menarini, Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Pfizer, Roche, Sanofi, Dong-A ST; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Lilly, Daiichi Sankyo, Pfizer, Novartis, Roche, Everest, Merck Sharp & Dohme, Menarini. S. Im: Financial Interests, Personal, Advisory Board: AstraZeneca, Hanmi, Idience, Lilly, MSD, GSK, Pfizer, Novartis, Roche, Daiichi Sankyo; Financial Interests, Personal, Research Grant: AstraZeneca, Daewoong Pharm, Eisai, Pfizer, Roche. K.S. Lee: Financial Interests, Institutional, Research Grant: Donga-ST; Financial Interests, Personal, Advisory Role: Pfizer, Novartis, MSD, Eisai, Lilly, Roche, Bixink, Everest Medicine, Daiichi Sankyo. D. Dastur: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Ownership Interest: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Non-Financial Interests, Personal, Project Lead: AstraZeneca. V. Haddad, S. Khan: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. B. Xu: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis. B. Pistilli: Financial Interests, Personal, Invited Speaker: AstraZeneca, Pierre-Fabre, Myriad; Financial Interests, Personal, Advisory Board: AstraZeneca, Pierre-Fabre, Daiichi Sankyo; Non-Financial Interests, Personal, Principal Investigator: Daiichi Sankyo, AstraZeneca, Pierre-Fabre, Merus, Puma; Financial Interests, Personal, Other, travel grant: Pfizer, Gilead. H.S. Rugo: Financial Interests, Personal, Advisory Board: Puma, Napo, Samsung; Financial Interests, Institutional, Research Grant: AstraZeneca, Ayala, BI, Daichii Sankyo, Genentech, Gilead, Lilly, Merck, Novartis, OBI Pharma, Pfizer, Polyphor, Sermonix, Seattle Genetics. All other authors have declared no conflicts of interest.