LBA11 - Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Primary results from the randomised phase III TROPION-Breast01 trial

Background

The TROP2-directed antibody-drug conjugate Dato-DXd demonstrated promising activity in heavily pre-treated patients (pts) with inoperable or metastatic HR+/HER2-BC in the Phase 1 TROPION-PanTumor01 trial (NCT03401385). Here we report primary PFS results from the global, Phase 3 TROPION-Breast01 trial (NCT05104866).

Methods

Adult pts with inoperable or metastatic HR+/HER2-BC, who had experienced progression on endocrine therapy (ET) and for whom ET was unsuitable, and who had received 1-2 prior lines of systemic chemotherapy (CT), were randomised 1:1 to Dato-DXd (6 mg/kg Q3W) or investigator’s choice of CT (ICC; eribulin, vinorelbine, capecitabine, or gemcitabine) until progression or unacceptable toxicity. Dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1, and overall survival (OS).

Results

732 pts were randomised (Dato-DXd: 365; ICC: 367). Median age (range) was 56 (29–86)/54 (28–86) yrs in the Dato-DXd/ICC groups. At data cut-off (17 Jul 2023), 93/39 pts in the Dato-DXd/ICC groups were ongoing treatment. Results are shown in the table. Pts receiving Dato-DXd had significantly improved PFS vs ICC (HR 0.63 [95% CI 0.52–0.76]; p<0.0001). OS data were not mature; a trend for improvement favouring Dato-DXd was observed. Pts receiving Dato-DXd had lower rates of grade ≥3 TRAEs and dose reductions vs ICC (Table).

Conclusions

TROPION-Breast01 met the primary endpoint of PFS; the study continues to final OS. Pts receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS compared with ICC, along with a favourable and manageable safety profile. Results support Dato-DXd as a novel treatment option for pts with inoperable or metastatic HR+/HER2-BC who have received 1–2 prior lines of CT. Table: LBA11

∗23% maturity.AEs, adverse events; mo, months; ORR, objective response rate; TRAEs, AEs possibly related to study treatment.

Clinical trial identification

NCT05104866; release date November 3, 2021.

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, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca PLC in collaboration with Daiichi Sankyo.

Funding

AstraZeneca PLC in collaboration with Daiichi-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, Institutional, Research Grant: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly. K. Jhaveri: Financial Interests, Personal, Advisory Role: AbbVie, AstraZeneca, Blueprint Medicines, Biotheranostics, BMS, Genentech/Roche, Jounce Therapeutics, Lilly Pharmaceuticals/Loxo Oncology, Novartis, Pfizer, Seattle Genetics, SunPharma Pvt Ltd, Taiho Oncology, Eisai, Gilead, Zymeworks, Scorpion Therapeutics, Daiichi; Financial Interests, Institutional, Research Funding: ADC Therapeutics, AstraZeneca, Clovis Oncology, Debiopharm, Genentech, Gilead, Novartis, Eli Lilly/Loxo Oncology, Merck/VelosBio, Novartis, Novita Pharmaceuticals, Pfizer, Puma Biotechnology, Scorpion Therapeutics and Zymeworks. S-A. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi-Sankyo and Idience; Financial Interests, Institutional, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Daewoong; Financial Interests, Institutional, Local PI, Clinical Trial Budget: AstraZeneca, Hanmi, Novartis, Roche, Pfizer, Daiichi-Sankyo, MSD, Eli Lilly; Financial Interests, Institutional, Coordinating PI, Clinical Trial Budget: Eisai; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. S. Pernas Simon: Financial Interests, Personal, Advisory Board: Seagen, AstraZeneca- Daiichi-Sankyo, Pierre-Fabre, Pfizer, Eisai, Novartis, Polyphor, Roche, Seattle Genetics; Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Eisai, Roche; Financial Interests, Institutional, Local PI: AstraZeneca, Novartis, Daiichi-Sankyo; Non-Financial Interests, Member of Board of Directors: SOLTI. M. De Laurentiis: Financial Interests, Personal, Invited Speaker: Novartis, Eli Lilly, Pfizer, Roche, Sanofi, MSD, Seagen, Gilead, Exact Science, Daiichi-Sankyo, AstraZeneca, and Eisai; Financial Interests, Personal, Principal Investigator: Novartis, Eli Lilly, Pfizer, Roche, Sanofi, MSD, Seagen, Gilead, Daiichi-Sankyo, AstraZeneca, and Eisai. S. Wang: Financial Interests, Personal, Invited Speaker: Pfizer, Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Local PI: Pfizer, AstraZeneca, Roche; Financial Interests, Personal and Institutional, Research Grant: Pfizer. N. Martínez: Financial Interests, Personal, Invited Speaker: Novartis, Lilly, Pfizer, Roche, Seagen, Gilead, Daiichi-Sankyo, AstraZeneca, and Eisai; Financial Interests, Personal, Principal Investigator: Novartis, Eli Lilly, Pfizer, Roche, Sanofi, MSD, Seagen, Gilead, Daiichi-Sankyo, AstraZeneca, and Eisai. G. Santos Borges: Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Daiich-Sankyo. D.W. Cescon: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Exact Sciences, Eisai, Gilead, GSK, Eli Lilly, Merck, Novartis, Pfizer and Roche; Financial Interests, Institutional, Research Funding: AstraZeneca, Gilead, GSK, Inivata, Knight Therapeutics, Merck, Pfizer, and Roche; Financial Interests, Personal, Licencing Fees or royalty for IP: Patent (US62/675,228). M. Hattori: Financial Interests, Personal, Speaker’s Bureau: Daiichi-Sankyo, Eli Lilly. Y-S. Lu: Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, MSD, Roche, Pfizer, AstraZeneca, Eisai, Daiichi-Sankyo, Gilead and Europharma; Financial Interests, Institutional, Local PI: Novartis, Roche, Pfizer, MSD, Eli Lily, Eisai, AstraZeneca, Gilead, Jellox; Non-Financial Interests, Leadership Role, Chair or co-chair of steering committee of clinical trials: Novartis. Financial Interests, Institutional, Research Grant: Novartis, Pfizer, MSD, Roche, AstraZeneca and ACT Genomics. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, iTeos Therapeutics, Janssen, Loxo, Relay Therapeutics, Olema Pharmaceuticals, Orum Therapeutics, Stemline Therapeutics, AstraZeneca, Daiichi-Sankyo, Seagen, Ellipses Pharma, Greenwich LifeSciences, Tubulis, Verascity Science, Theratechnologies, Puma Biotechnology, Boehringer Ingelheim, Silverback Therapeutics, Black Diamond Therapeutics, CytomX Therapeutics, Dantari, H3 Biomedicine, Merck, Seagen, Eisai, Deciphera, Arvinas, Arcus Biosciences ; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond Therapeutics, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Onconova Therapeutics, Dana Farber Cancer Inst, Hutchinson MediPharma, MedImmune, Seagen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, AbbVie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi-Sankyo, Syros, Sutro Biopharma, G1 Therapeutics, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses Pharma, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicines, Treadwell Therapeutics, Accutar Biotechnology, Artios, BeiGene, Bliss BioPharmaceuticals, Cascadian Therapeutics, Context Therapeutics, Cullinan, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Tolmar, Torque Therapeutics, Merck, Myriad Genetics, Silverback Therapeutics, Vincerx and Fochon Pharmaceuticals. J. Tsurutani: Financial Interests, Personal, Invited Speaker: Daiichi-Sankyo, AstraZeneca, Eisai; Financial Interests, Personal, Expert Testimony: Daiichi-Sankyo; Financial Interests, Institutional, Research Funding: Daiichi-Sankyo, Eisai, FSJD, WJOG; Financial Interests, Personal, Principal Investigator: Daiichi-Sankyo, Eisai, Seagen, Taiho, Eli Lilly, MSD, Oncotherapy. K. Kalinsky: Financial Interests, Personal, Advisory Board: Daiichi-Sankyo, Eli Lilly, Pfizer, Novartis, Eisai, AstraZeneca, Immunomedics, Merck, Seattle Genetics, Cyclacel, Oncosec, 4D Pharma, Puma Biotechnology; Financial Interests, Personal and Institutional, Local PI, Consultant: Novartis, Daiichi-Sankyo, Eli Lilly, AstraZeneca; Financial Interests, Personal, Stocks/Shares, Employment + Stock = spouse: Grail, Array BioPharma and Pfizer; Financial Interests, Personal and Institutional, Local PI, consultant: Genentech; Financial Interests, Institutional, Local PI, consultant: Pfizer; Financial Interests, Institutional, Local PI: Seattle Genetics, Ascentantage; Financial Interests, Personal, Other, Consultant: Myovant, Takeda, Menarini; Financial Interests, Personal, Other, consultant: Menarini; Other, Support for attending meetings and/or travel: Eli Lilly, AstraZeneca, Pfizer; Other, Steering Committee: Immunomedics, AstraZeneca, Ambryx, Genentech. L. Xu, N. Denduluri: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: Puma Biotechnology, NAPO, Blueprint, Mylan, Daiichi-Sankyo, Eisai and Scorpion Therapeutics; Financial Interests, Institutional, Local PI: Novartis, Lilly, Pfizer, Daiichi-Sankyo, AstraZeneca, Gilead, GSK, Sermonix Pharmaceuticals, Pionyr Immunotherapeutics, Taiho Oncology, Inc., Veru Inc; Financial Interests, Institutional, Coordinating PI: OBI Pharma, Astellas Pharma Inc., F. Hoffmann-La Roche AG/Genentech, Inc., Merck; Financial Interests, Personal, Other, Travel support to academic meetings: Merck, AstraZeneca, Gilead; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various; Financial Interests, Institutional, Research Grant: Astellas Pharma, AstraZeneca; Daiichi-Sankyo, Roche/Genentech, Gilead, GSK, Eli Lilly, Merck & Co., Novartis, OBI Pharma, Pfizer, Pionyr, Immunotherapeutics, Sermonix Pharmaceuticals, Taiho Oncology and Veru Inc. B. Xu: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer, and Roche; Financial Interests, Personal, Advisory Board: AstraZeneca and Novartis. B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca, Seagen, Eli Lilly, Daiichi-Sankyo, Gilead, MSD, Novartis, Pierre-Fabre; Financial Interests, Institutional, Invited Speaker: Gilead, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi-Sankyo; Financial Interests, Personal, Other, travel support: AstraZeneca, Pierre Fabre, MSD, Daiichi-Sankyo; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi-Sankyo, Gilead, Seagen; Financial Interests, Institutional, Local PI: AstraZeneca, Gilead, Seagen, MSD, Novartis; Financial Interests, Institutional, Funding: Daiichi-Sankyo; Non-Financial Interests, , Project Lead: UNICANCER. All other authors have declared no conflicts of interest.