Abstract 1436TiP
Background
T-DXd is an antibody–drug conjugate of an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a topoisomerase I inhibitor. T-DXd is approved globally to treat HER2-positive (HER2+) metastatic breast cancer, and in the US and Japan to treat advanced HER2+ GC. In the primary analysis of DESTINY-Gastric01 (DS8201-A-J202; NCT03329690), an open-label, multicenter, randomized, phase II trial in pts with HER2+ advanced GC or GEJ adenocarcinoma, T-DXd demonstrated clinically relevant improvement compared with standard of care in objective response rate (ORR; 51% vs 14%; P < 0.001) and overall survival (OS) benefit (12.5 vs 8.4 mo; hazard ratio [HR] 0.59 [95% CI 0.39-0.88]; P = 0.01) in the third-line or later (Shitara, N Engl J Med 2020). The DG-04 study aims to evaluate the efficacy and safety of T-DXd vs the combination of ramucirumab (ram) and paclitaxel (ptx) in pts with HER2+ GC or GEJ adenocarcinoma in the second-line setting.
Trial design
DG-04 (NCT04704934) is a phase III, global, multicenter, randomized, open-label study in pts with HER2+ metastatic and/or unresectable GC or GEJ adenocarcinoma. Eligible pts must be adults (according to local regulations), with an ECOG performance status of 0 or 1, with documented GC or GEJ adenocarcinoma that has been previously treated in the metastatic first-line setting with a trastuzumab (tmab)-containing regimen. HER2-positivity (IHC3+ or IHC2+/ISH+) must be centrally confirmed on tumor biopsies obtained after progression on or after tmab. Pts must not have received anticancer therapy after a first-line tmab-containing regimen. Pts will be randomized 1:1 to receive T-DXd (6.4 mg/kg every 3 weeks) or ram (8 mg/kg on days 1 and 15 of a 28-day cycle) in combination with ptx (80 mg/m2 on days 1, 8, and 15 of a 28-day cycle). This study is actively enrolling with approximately 490 participants planned. The primary endpoint is OS. Secondary endpoints include progression-free survival, ORR, duration of response, disease control rate, safety, pharmacokinetics, and immunogenicity of T-DXd.
Clinical trial identification
NCT04704934.
Editorial acknowledgement
Under the guidance of authors, assistance in medical writing and editorial support was provided by Laura Halvorson, PhD, of ApotheCom.
Legal entity responsible for the study
Daiichi Sankyo, Inc., and AstraZeneca.
Funding
This study was funded by Daiichi Sankyo, Inc., and AstraZeneca.
Disclosure
K. Shitara: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: ONO Pharmaceutical; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: TAIHO Pharmaceutical; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Yakult Honsha; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: AbbVie; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: ONO Pharmaceutical; Financial Interests, Institutional, Research Grant: Sumitomo Dainippon; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: TAIHO Pharmaceutical; Financial Interests, Institutional, Research Grant: CHUGAI Pharmaceutical; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Medi Science; Financial Interests, Institutional, Research Grant: Eisai. J. Seraj: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Kawaguchi: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. L. Shen: Financial Interests, Personal, Advisory Board: Rongchang pharmaceutica; Financial Interests, Personal, Advisory Board: ZaiLab; Financial Interests, Personal, Advisory Board: CStone Pharmaceutical; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Mingji biopharmaceutical; Financial Interests, Personal, Advisory Role: Haichuang pharmaceutical; Financial Interests, Personal, Advisory Role: Herbour biomed; Financial Interests, Personal, Advisory Role: BI; Financial Interests, Personal, Speaker’s Bureau: Hutchison Whampoa; Financial Interests, Personal, Speaker’s Bureau: Hengrui; Financial Interests, Personal, Speaker’s Bureau: ZaiLab; Financial Interests, Personal, Speaker’s Bureau: CStone Pharmaceutical; Financial Interests, Institutional, Research Grant: Beijing Xiantong Biomedical Technology; Financial Interests, Institutional, Research Grant: Qilu Pharmaceutical; Financial Interests, Institutional, Research Grant: ZaiLab Pharmaceutical (Shanghai); Financial Interests, Institutional, Research Grant: Beihai Kangcheng(Beijing)Medical Technology; Financial Interests, Institutional, Research Grant: Jacobio Pharmaceuticals. T. Kamio: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. G. Meinhardt: Financial Interests, Personal and Institutional, Stocks/Shares: Daiichi Sankyo; Financial Interests, Personal and Institutional, Full or part-time Employment: Daiichi Sankyo. J. Tabernero: Financial Interests, Personal, Other, Honoraria: Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER); Financial Interests, Personal, Advisory Role: Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati; Financial Interests, Institutional, Research Grant: Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Janssen-Ci; Financial Interests, Personal, Officer: Spanish Association Against Cancer (AECC), Oslo University Hospital Comprehensive Cancer Center, Oncode Institute, National Decade Against Cancer (NCT)-German Consortium for Translational Cancer Research (DKTK), Karolinska Comprehensive Cancer Center, Ins; Non-Financial Interests, Personal, Principal Investigator: Array Biopharma, AstraZeneca Pharmaceutical, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Debiopharm, F.Hoffmann-La Roche, Genentech, HalioDX, Hutchinson Mediapharma, Janssen-Cilag Intl, MedImmune, Menarini, Merck Healthcare KGAA, MSD, M; Financial Interests, Personal, Leadership Role: World Innovative Networking (WIN)Consortium in Personalized Cancer Medicine; Financial Interests, Personal, Leadership Role: European Organization for Research and Treatment of Cancer-EORTC; Financial Interests, Personal, Member of the Board of Directors: Cancer Core Europe; Financial Interests, Personal, Member of the Board of Directors: Horizon Europe Cancer Mission. All other authors have declared no conflicts of interest.