海报库PosterKeep
当前会议AACR 2026返回检索会员登录
LBPO.CL03 · 临床研究 · Late-Breaking

First-line (1L) trastuzumab deruxtecan (T-DXd) + rilvegostomig (rilve) + fluoropyrimidine (FP) in HER2-positive (HER2+) gastric cancer (GC), gastroesophageal junction adenocarcinoma (GEJA), or esophageal adenocarcinoma (EA): DESTINY-Gastric03 (DG-03) Part 4 arm A results

海报缩略图：First-line (1L) trastuzumab deruxtecan (T-DXd) + rilvegostomig (rilve) + fluoropyrimidine (FP) in HER2-positive (HER2+) gastric cancer (GC), gastroesophageal junction adenocarcinoma (GEJA), or esophageal adenocarcinoma (EA): DESTINY-Gastric03 (DG-03) Part 4 arm A results
编号 LB331 展板 12 时间 4/21 02:00–05:00 区域 Section 52 主讲 Yelena Janjigian, MD
分会场 Late-Breaking Research: Clinical Research 3
查看完整资料 下载 PDF 登录后可访问当前开放资料 AACR 官方页面 ↗

作者与单位

Yelena Y. Janjigian1, Hanneke van Laarhoven2, Hirokazu Shoji3, Lucjan Wyrwicz4, Sara Lonardi5, Boguslawa Karaszewska6, Xinjun Liang7, Aitana Calvo Ferrándiz8, Mariusz Kwiatkowski9, Keun-Wook Lee10, Tianshu Liu11, Kohei Shitara12, Sun Young Rha13, Salvatore Siena14, Roy Rabbie15, Caron Lloyd16, Megan Scott17, Arthur W. Lambert18, Jeeyun Lee19

1Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center, New York, NY,2Department of Medical Oncology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands,3Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan,4Klinika Onkologii i Radioterapii, Narodowy Instytut Onkologii, Warsaw, Poland,5Department of Medical Oncology, Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy,6Department of Oncology, Regional Polyclinical Hospital in Konin, Konin, Poland,7Department of Medical Oncology, Hubei Cancer Hospital, Wuhan, China,8Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain,9Oncology Clinic, Nicolaus Copernicus Provincial Hospital in Koszalin, Koszalin, Poland,10Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea, Republic of,11Department of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, China,12Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan,13Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, Republic of,14Department of Oncology and Hemato-Oncology, Università degli Studi di Milano and Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy,15Global Medicines Development, Late Development Oncology, Oncology R&D, AstraZeneca, Cambridge, United Kingdom,16Global Medicines Development, Late Development Oncology, Oncology R&D, AstraZeneca, New York, NY,17Oncology Biometrics, Oncology R&D, AstraZeneca, Cambridge, United Kingdom,18Translational Medicine, Oncology R&D, AstraZeneca, Waltham, MA,19Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of

摘要 Abstract

Background: T-DXd monotherapy is approved in several countries for advanced HER2+ GC/GEJA after an indicated HER2-directed regimen. 1L rilve (a monovalent, Fc-reduced, bispecific IgG1 antibody against PD-1 and TIGIT receptors) + chemotherapy showed encouraging efficacy and a manageable safety profile in advanced GCs. We report early data from DG-03 Part 4 arm A evaluating 1L T-DXd + rilve + FP in HER2+ GCs. Methods: DG-03 (NCT04379596) is a Phase 1b/2, open-label, multipart trial. Part 4 arm A enrolled patients (pts) with previously untreated advanced/metastatic HER2+ (IHC 3+ or IHC 2+/ISH+; local test) GC/GEJA/EA. Pts received T-DXd + rilve + FP (5-fluorouracil or capecitabine). PD-L1 status was assessed by central test retrospectively. Primary endpoint was confirmed objective response rate (ORR) by investigator assessment (INV) per RECIST 1.1; safety was also assessed. Results: At data cutoff (Oct 16, 2025), 30 pts were enrolled and received treatment (Tx). Median duration of follow up was 7.6 (range, 1.9-12.6) months; median duration of Tx exposure for T-DXd and rilve was 7.0 (range, 1.8-11.3) months. Confirmed ORR by INV (n/n) was 70% (21/30) overall, 78% (18/23) and 50% (3/6) in pts with HER2 IHC 3+ and IHC 2+/ISH+ tumors, and 82% (9/11) and 50% (3/6) in pts with PD-L1 CPS ≥1 and CPS <1 tumors, respectively. Safety data are shown in the Table. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 2 pts (7%; both Grade 2); there were no reports of drug-related left ventricular dysfunction. Conclusions: Early results showed promising antitumor activity with 1L T-DXd + rilve + FP in HER2+ GCs; safety findings were generally consistent with the known profiles of each agent as monotherapy, with no new safety signals observed. Data support further study of this 1L triplet regimen in HER2+ GCs. n (%) HER2+ (arm A; N=30) AEs 29 (97) Drug-related AEs* 26 (87) Grade ≥3 AEs 11 (37) Drug-related Grade ≥3 AEs* 8 (27) Serious AEs 8 (27) Drug-related serious AEs* 4 (13) AEs leading to dose interruption of T-DXd / rilvegostomig 10 (33) / 11 (37) AEs leading to dose reduction of T-DXd / rilvegostomig 3 (10) / 0 AEs leading to discontinuation of any treatment 4 (13) Drug-related AEs leading to death* 0 *Assessed by the investigator as possibly related to any treatment AE, adverse event; HER2+, HER2-positive; T-DXd, trastuzumab deruxtecan
利益披露 Disclosure
Y. Y. Janjigian, Abbvie; AmerisourceBergen; Arcus Biosciences; AskGene Pharma; Astellas Pharma; AstraZeneca; Basilea Pharmaceutical; Bayer; Boehringer Ingelheim; Bristol-Myers Squibb; Clinical Care Options Other, Consulting or advisory role. Daiichi Sankyo; Debbies Dream Foundation; Eisai; Genzyme; Geneos; GlaxoSmithKline; Guardant Health; H.C. Wainwright & Co.; HMP Education; Imedex; Imugene; Inspirna; Jazz Pharmaceuticals Other, Consulting or advisory role. Lilly; Lynx Health; Merck; Merck Serono; Mersana; Michael J. Hennessy Associates; OncLive; OncoDaily; Paradigm; Peerview; Pfizer; Physicans' Education Resource; Research to Practice; Seagen Other, Consulting or advisory role. Signatera; Silverback Therapeutics; WebMD; Zymeworks Other, Consulting or advisory role. Bristol-Myers Squibb Japan; Merck Travel. Axis Medical Education; Clinical Care Options; Giants of Cancer Care; Research to Practice Other, Other relationships. Inspirna; OncoDaily; Veeda Oncology Stock, Stock Option. Abbvie; AmerisourceBergen; Arcus Biosciences; AskGene Pharma; Astellas Pharma; AstraZeneca; Basilea Pharmaceutical; Bayer; BeOne Medicines; Boehringer Ingelheim; Bristol-Myers Squibb Other, Honoraria. Clinical Care Options; Daiichi Sankyo; eChinaHealth; Eisai; Geneos; Genzyme; Gilead Sciences; GlaxoSmithKline; Guardant Health; H.C. Wainwright & Co.; HMP Education; IDEOlogy Health; Imedex; Imugene Other, Honoraria. i3 Health; Inspirna; Lilly; Lynx Health; Master Clinician Alliance; Merck; Merck Serono; Mersana; Michael J. Hennessy Associates; Oncology Information Group; Paradigm; Peerview; Pfizer Other, Honoraria. Physicans' Education Resource; Regeneron; Research to Practice; Seagen; Silverback Therapeutics; Suzhou Liangyihui Network Technology; Talem Health; TotalCME; WebMD; Zymeworks Other, Honoraria. Arcus Biosciences; Astellas Pharma; AstraZeneca; Bayer; Bristol-Myers Squibb; Cycle for Survival; Department of Defense; Fred's Team; Genentech/Roche; Inspirna; Lilly; Merck; NCI; Stand up to Cancer ). Transcenta ). H. van Laarhoven, Amgen; Amphera; Astellas Pharma; AstraZeneca; BeiGene; Boehringer Ingelheim; Bristol-Myers Squibb; Daiichi Sankyo; MSD Oncology; MyeoloidTx Other, Consulting or advisory role. AstraZeneca; Bristol-Myers Squibb; CongressCare; Daiichi Sankyo; MedTalks; Travel Congress Management; Uitgeverij Jaap Other, Speakers' Bureau. AstraZeneca Travel. Amgen; Auristone; Bristol-Myers Squibb; Incyte; Merck KGaA; ORCA Therapeutics; Servier ). H. Shoji, Astellas Pharma Other, Consulting or advisory role. AbbVie; Amgen; Astellas Pharma; AstraZeneca; Daiichi Sankyo; Elevation Oncology; MSD; Ono Pharmaceutical; Takeda ). L. Wyrwicz, None. S. Lonardi, Amgen; Astellas Pharma; AstraZeneca; Bayer; Beigene; Bristol-Myers Squibb; Daiichi Sankyo; GSK; Helion; Incyte; Lilly; Merck Serono; MSD; Nimbus Therapeutics; Rottapharm; Servier; Takeda Other, Advisory board. Amgen; AstraZeneca; Bristol-Myers Squibb; GlaxoSmithKline; Incyte; Lilly; Merck Serono; MSD; Pierre-Fabre; Roche; Servier Other, Invited speaker. Amgen; AstraZeneca; Bayer; Bristol-Myers Squibb; Lilly; Merck Serono; Roche Other, Coordinating PI. GONO Foundation g., Board of Directors, non-salaried role). B. Karaszewska, None.. X. Liang, None. A. Calvo Ferrándiz, AstraZeneca; Daiichi Sankyo; MSD Other, Advisory board. Amgen; Astellas Pharma; AstraZeneca; BMS; MSD Other, Invited speaker. M. Kwiatkowski, None. K. Lee, Abbvie; Astellas Pharma; BeiGene; Daiichi Sankyo; Metafines; MSD; Ono Pharmaceutical; PIN therapeutics; Takeda Other, Consulting or advisory role. Astellas Pharma; Bayer; Celltrion; Merck KGaA; MSD Oncology; Ono Pharmaceutical Other, Honoraria. ALX Oncology; Amgen; Arcus Biosciences; Astellas Pharma; AstraZeneca; Avelos Therapeutics; Bayer; BeiGene; Boehringer Ingelheim; Bolt Biotherapeutics; Daiichi Sankyo; Erasca, Inc; Exelixis ). Genome & Company; GlaxoSmithKline; Hanmi; IDRx; IgM Biosciences; Ildong Pharmaceutical; InventisBio; Jazz Pharmaceuticals; Jiangsu Hengrui Pharmaceuticals; Leap Therapeutics; MedPacto; Medicenna ). Merk KGaA; Metafines; MSD; Ono Pharmaceutical; Panolos Bioscience; Pfizer; Roche; Taiho Pharmaceutical; Torl Biotherapeutics; Trishula Therapeutics; Wellmarker Bio; Yuhan ). ALX Oncology Other, Uncompensated relationship. T. Liu, None. K. Shitara, Astellas Pharma; AstraZeneca; Bristol-Myers Squibb; Janssen; Lilly; Ono Pharmaceutical Other, Honoraria. Abbvie; ALX Oncology; Amgen; Arcus Biosciences Inc.; Astellas Pharma; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol-Myers Squibb; CMIC Co., Ltd.; Daiichi Sankyo; Elevation Oncology Other, Consulting or advisory role. eChainaHealth, Inc.; Gilead Sciences; GlaxoSmithKline K.K.; Guardant Health; Healios; Janssen; Leap Therapeutics; Levolution Medicines, Inc.; Moderna Inc; MSD; Novartis; Oncolys BioPharma Other, Consulting or advisory role. Ono Pharmaceutical; Phanes Therapeutics; Sanofi; Scandion Oncology; Suzuhou Liangyihui Network Technology Co.; Takeda; Zymeworks Other, Consulting or advisory role. Amgen; Astellas Pharma; AstraZeneca; Chugai Pharma; Daiichi Sankyo; Eisai; Insyte Biosciences G.K.; Medpace Japan K.K.; MSD; Ono Pharmaceutical; PRA Health Sciences; PPD-SNBL; Syneos Health ). Taiho Pharmaceutical; Toray Industries ). S. Y. Rha, Amgen; Arcus Biosciences; Astellas Pharma; AstraZeneca; BeOne Medicines; Daiichi Sankyo; Eisai; indivumed; LG Chem; MSD Oncology; Ono Pharmaceutical; Toray Industries Other, Consulting or advisory role. Amgen; Astellas Pharma; AstraZeneca; Bristol-Myers Squibb/Ono Pharmaceutical; Daiichi Sankyo/UCB Japan; Eisai; MSD Oncology Other, Speakers' Bureau. S. Siena, Agenus; AstraZeneca; BMS; Checkmab; Daiichi Sankyo; GSK; Merck; MSD; Novartis; Seagen; T-One-Therapeutics Other, Advisory board. R. Rabbie, AstraZeneca Employment, Stock, Stock Option. C. Lloyd, AstraZeneca Employment, Stock, Stock Option. M. Scott, AstraZeneca Employment, Stock, Stock Option. A. W. Lambert, AstraZeneca Employment, Stock, Stock Option. J. Lee, Amgen; AstraZeneca; Daiichi Sankyo; Guardant Health AMEA; Immunoncia; Mirati Therapeutics; Trutino Biosciences Other, Consulting or advisory role. AstraZeneca; Merck Sharp & Dohme; Samsung Bioepis ).

在会议检索中打开