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LBPO.CL01 · 临床研究 · Late-Breaking

First-line (1L) trastuzumab deruxtecan (T-DXd) regimens in advanced HER2-positive (HER2+) gastric cancer (GC), gastroesophageal junction adenocarcinoma (GEJA), or esophageal adenocarcinoma (EA): Exploratory analysis of baseline HER2-related biomarkers in DESTINY-Gastric03 (DG-03) Part 2

海报缩略图：First-line (1L) trastuzumab deruxtecan (T-DXd) regimens in advanced HER2-positive (HER2+) gastric cancer (GC), gastroesophageal junction adenocarcinoma (GEJA), or esophageal adenocarcinoma (EA): Exploratory analysis of baseline HER2-related biomarkers in DESTINY-Gastric03 (DG-03) Part 2
编号 LB010 展板 10 时间 4/19 02:00–05:00 区域 Section 50 主讲 Yelena Janjigian, MD
分会场 Late-Breaking Research: Clinical Research 1
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作者与单位

Yelena Y. Janjigian1, Hanneke van Laarhoven2, Sun Young Rha3, Vadim Kozlov4, Keun-Wook Lee5, Do-Youn Oh6, Adriano Gravina7, Min-Hee Ryu8, Liane Rapatoni9, Luís Antunes10, Filippo Pietrantonio11, Hirokazu Shoji12, Ralf-Dieter Hofheinz13, Maxime Chénard-Poirier14, Li-Tzong Chen15, Aleksandr Vasiliev16, Svetlana Kutukova17, Arthur W. Lambert18, Kun Yu19, Megan Scott20, Roy Rabbie21, Jeeyun Lee22

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 Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, Republic of,4State Budgetary Health Care Institution, Novosibirsk Regional Clinical Oncology Dispensary, Novosibirsk, Russian Federation,5Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea, Republic of,6Department of Internal Medicine, Seoul National University Hospital Cancer, Research Institute, Seoul, Korea, Republic of,7SC Sperimentazioni Cliniche, Istituto Nazionale Tumori, IRCCS, Fondazione Pascale, Naples, Italy,8Department of Oncology, Asan Medical Center, Seoul, Korea, Republic of,9Division of Clinical Oncology, Department of Medical Imaging, Haematology and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil,10University Hospital of Santa Maria, Federal University of Santa Maria, and Viver Research Center, Santa Maria, Brazil,11Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy,12Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan,13Mannheim Cancer Center, University of Heidelberg, Heidelberg, Germany,14Hematology and Medical Oncology Department, CHU de Québec, Québec, QC, Canada,15Kaohsiung Medical University Hospital, and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan,16Clinical Research Department, RZD Medicine Clinical Hospital of Saint Petersburg, Saint Petersburg, Russian Federation,17Municipal Clinical Oncology Dispensary, Pavlov University, Saint Petersburg, Russian Federation,18Translational Medicine, Oncology R&D, AstraZeneca, Waltham, MA,19Oncology Data Science & AI, Oncology R&D, AstraZeneca, Waltham, MA,20Oncology Biometrics, Oncology R&D, AstraZeneca, Cambridge, United Kingdom,21Global Medicines Development, Late Development Oncology, Oncology R&D, AstraZeneca, Cambridge, United Kingdom,22Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of

摘要 Abstract

Background: DG-03 Part 2 showed promising antitumor activity for 1L T-DXd regimens in advanced HER2+ GCs. We report concordance rates between local and central HER2 IHC results, and ORRs according to baseline HER2-related biomarkers, in DG-03 Part 2. Methods: DG-03 (NCT04379596) is a Phase 1b/2, open-label, multipart trial. In Part 2, patients (pts) with previously untreated advanced HER2+ (IHC 3+ or IHC 2+/ISH+; local test) GC/GEJA/EA were enrolled across six arms and received either trastuzumab + chemotherapy (CT; fluoropyrimidine [FP; 5-fluorouracil or capecitabine] + cisplatin/oxaliplatin), T-DXd 6.4 mg/kg, T-DXd 6.4 mg/kg + FP, T-DXd 6.4 mg/kg + FP + pembrolizumab (pembro), T-DXd 6.4 mg/kg + pembro, or T-DXd 5.4 mg/kg + FP + pembro. Confirmed investigator-assessed ORRs were reported by local and central HER2 IHC/ISH status (HercepTest for central IHC) and by plasma (GuardantOMNI) and tumoral (FoundationOne CDx) HER2 (ERBB2) amplification (amp). Results: As of Feb 28, 2025, 230 pts were enrolled; 229 received treatment. Overall (n/N), 80% (160/199) of HER2+ (IHC 3+ or IHC 2+/ISH+) GCs by local test were centrally scored as HER2+; 86% (143/166) and 52% (17/33) of IHC 3+ and IHC 2+/ISH+ GCs by local test were centrally scored as HER2+, respectively (missing/unknown data for n=2 local IHC, n=1 local ISH, n=3 central ISH, and n=24 central IHC results). Baseline HER2-related biomarker analyses are in the Table. Conclusions: Concordance results were broadly consistent with prior studies in GC. Elevated baseline HER2 IHC expression and HER2 amp were generally associated with higher ORRs for pts with HER2+ GCs treated with 1L T-DXd regimens, versus those with lower HER2 expression and/or without amplified HER2 . Data provide further evidence of antitumor activity for 1L T-DXd combinations in HER2+ GCs. ORR %; 95% CI n/N Trastuzumab + CT T-DXd T-DXd + FP T-DXd 6.4 mg/kg + FP + pembro T-DXd + pembro T-DXd 5.4 mg/kg + FP + pembro n 29 43 41 43 41 32 Local* IHC 3+ 77 ; 56, 91 20/26 57 ; 40, 73 21/37 80 ; 63, 92 28/35 60 ; 42, 76 21/35 63 ; 44, 79 20/32 73 ; 52, 88 19/26 IHC 2+/ISH+ 67 ; 9, 99 2/3 0 ; 0, 52 0/5 60 ; 15, 95 3/5 57 ; 18, 90 4/7 67 ; 30, 93 6/9 83 ; 36, 100 5/6 Central* IHC 3+ / IHC 2+/ISH+ 79 ; 54, 94 15/19 58 ; 39, 76 18/31 81 ; 64, 93 26/32 65 ; 47, 80 22/34 65 ; 44, 83 17/26 70 ; 46, 88 14/20 IHC 2+/ISH− / IHC 1+/0 100 ; 40, 100 4/4 14 ; 0, 58 1/7 40 ; 5, 85 2/5 20 ; 1, 72 1/5 50 ; 21, 79 6/12 71 ; 29, 96 5/7 Tumor † Amp 90 ; 56, 100 9/10 63 ; 38, 84 12/19 76 ; 53, 92 16/21 63 ; 38, 84 12/19 71 ; 42, 92 10/14 - No amp 100 ; 29, 100 3/3 20 ; 1, 72 1/5 67 ; 9, 99 2/3 20 ; 1, 72 1/5 56 ; 21, 86 5/9 Plasma † Amp 73 ; 45, 92 11/15 68 ; 43, 87 13/19 87 ; 66, 97 20/23 68 ; 45, 86 15/22 94 ; 70, 100 15/16 82 ; 60, 95 18/22 No amp 75 ; 19, 99 3/4 23 ; 5, 54 3/13 60 ; 32, 84 9/15 23 ; 5, 54 3/13 35 ; 14, 62 6/17 60 ; 26, 88 6/10 Unknown results excluded *HER2 IHC/ISH; † HER2 amp
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 ). 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. V. Kozlov, None. K. Lee, Abbvie; Amgen; 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 ). Metafines; MSD; Ono Pharmaceutical; Panolos Bioscience; Pfizer; Roche; Taiho Pharmaceutical; Torl Biotherapeutics; Trishula Therapeutics; Wellmarker Bio; Yuhan ). ALX Oncology Other, Uncompensated relationship. D. Oh, Abbvie; Alligator Bioscience AB; Arcus Biosciences; Astellas; ASLAN; AstraZeneca; Basilea; Bayer; BeiGene; BMS/Celgene; Eutilex; Genentech/Roche; Halozyme; Hana Pharm; Hanmi; Idience; IQVIA; J-Pharma Other, Advisory board. Mirati Therapeutics, Eutilex, Moderna, Idience, Alligator Bioscience AB, Hana Pharm, Revolution Medicine, Tallac Therapeutics, Hanmi Other, Advisory board. Array; AstraZeneca; BeiGene; Eli Lilly; Handok; Hanmi; MSD; Novartis; Servier ). A. Gravina, None. M. Ryu, Astellas Pharma; AstraZeneca; BMS; DAE HWA Pharmaceutical; Daiichi Sankyo; Lilly; MSD; Novartis; Ono Pharmaceuticals; Taiho Pharmaceutical Other, Advisory board. AstraZeneca, BMS, Ono Pharmaceutical ). L. Rapatoni, None.. L. Antunes, None. F. Pietrantonio, Agenus; Amgen; AstraZeneca; BMS; BeOne; GSK; Incyte; Johnson&Johnson; Lilly; Rottapharm; Tempus ). Amgen; Astellas; AstraZeneca; Bayer; BMS; BeOne; Daiichi Sankyo; Incyte; Ipsen; Johnson & Johnson; Merck-Serono; MSD; Pierre-Fabre; Seagen; Servier; Takeda Other, Invited speaker. Agenus; Amgen; Astellas Pharma; AstraZeneca; Bayer; BMS; BeOne; Daiichi Sankyo; Gilead; GSK; Incyte; Italfarmaco; Jazz Pharmaceuticals; Johnson & Johnson; Merck-Serono; MSD; Pfizer; Pierre-Fabre Other, Advisory/consultancy. Revolution Medicine; Rottapharm; Servier; Takeda Other, Advisory/consultancy. Amgen; Astellas Pharma; Incyte; Johnson & Johnson; Merck-Serono; Pierre-Fabre; Servier Travel. H. Shoji, Astellas Pharma Other, Consulting or advisory role. AbbVie; Amgen; Astellas Pharma; AstraZeneca; Daiichi Sankyo; Elevation Oncology; MSD; Ono Pharmaceutical; Takeda ). R. Hofheinz, Abbvie; Amgen; Astellas Pharma; AstraZeneca; BeOne; Boehringer; BMS; Daiichi Sankyo; Esteve; INCYTE; Leo Pharma; Lilly; Merck; MSD; Nordic; Pierre-Fabre; Roche; Sanofi; Servier; Takeda; WALA Other, Advisory board and/or speaker fees. M. Chénard-Poirier, AstraZeneca; BMS; Incyte; Merck; Pfizer Other, Honoraria for advisory board and speaker fees. L. Chen, AbbVie; AstraZeneca; MSD; Revolution Medicine Other, Advisory board. BMS; Ipsen; Novartis; ONO Pharmaceuticals; PharmaEngine (TW); TTY (TW) Other, Invited speaker. Onward; ScinoPharm Taiwan Other, Advisory board and scientific advisory committee. AstraZeneca; ONO Pharmaceuticals; Pfizer; TransThera Other, Steering committee. GSK; Taiho Pharmaceutical Other, Local PI. Ipsen Other, Co-ordinating PI including medication and budget support for investigator-initiated trial in NET. Pfizer ). Syncore BioPharma; TTY, Taiwan Other, Trial Chair. OBI (TW) Other, DSMC member for clinical trials . Taivex (TW) Other, Medical Monitoring for clinical trial. ScinoPharm Taiwan, Ltd. g., Board of Directors, non-salaried role). HuniLife Biotechnology, Inc. Other Intellectual Property, Licencing fees for alpha-enolase specific antibodies. A. Vasiliev, None.. S. Kutukova, None. A. W. Lambert, AstraZeneca Employment, Stock, Stock Option. K. Yu, AstraZeneca Employment, Stock, Stock Option. M. Scott, AstraZeneca Employment, Stock, Stock Option. R. Rabbie, 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 ).

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