海报库PosterKeep
PO.CTP01.03 · 进行中的临床试验

OrigAMI-3：一项在复发、不可切除或转移性RAS/BRAF野生型结直肠癌参与者中比较amivantamab联合FOLFIRI与cetuximab或bevacizumab联合FOLFIRI的随机3期研究

OrigAMI-3: A randomized, phase 3 study of amivantamab plus FOLFIRI vs cetuximab or bevacizumab plus FOLFIRI in participants with recurrent, unresectable, or metastatic RAS / BRAF wild-type colorectal cancer

编号 CT216 展板 11 时间 4/21 09:00–12:00 区域 Section 51 主讲 Jenny Seligmann, PhD, MRCP
分会场 Phase II and Phase III Clinical Trials in Progress
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作者与单位 Authors & Affiliations

J. Randolph Hecht1, Elena Élez2, Cathy Eng3, Peter Gibbs4, Jenny Seligmann5, Ruihua Xu6, Kensei Yamaguchi7, Jaw Yuan Wang8, Hao Wei Teng9, Leonardo Trani10, Honeylet Wortman-Vayn11, Zhengyu Jiang10, Brooke Diorio12, Patricia Lorenzini12, Christine Baudelet13, Seema Sethi10, Mahadi Baig12, Chiara Cremolini14

1UCLA Jonsson Comprehensive Cancer Center, Santa Monica, CA,2Vall d'Hebron University Hospital, Barcelona, Spain,3Vanderbilt-Ingram Cancer Center, Nashville, TN,4Western Health Sunshine Hospital, St. Albans, Victoria, Australia,5St James University Hospital, Leeds, United Kingdom,6Sun Yat-Sen University Cancer Center, Guangzhou, China,7The Cancer Institute Hospital of JFCR, Tokyo, Japan,8Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan,9Taipei Veterans General Hospital, Taipei, Taiwan,10Johnson & Johnson, Spring House, PA,11Johnson & Johnson, Bridgewater, NJ,12Johnson & Johnson, Raritan, NJ,13Johnson & Johnson, Beerse, Belgium,14Azienda Ospedaliero Universitaria Pisana, Pisa, Italy

摘要 Abstract

中文摘要
背景：在转移性结直肠癌（mCRC）患者中，约50%为KRAS、NRAS和BRAF野生型（RAS/BRAF WT），且无可靶向的基因组改变。RAS/BRAF WT mCRC的标准一线治疗为以5-FU为基础的双药化疗（FOLFOX或FOLFIRI）联合抗EGFR或抗VEGF治疗。二线治疗的选择取决于一线治疗（例如，一线使用以奥沙利铂为基础的化疗时，二线须使用以伊立替康为基础的方案，反之亦然）。已知的抗EGFR治疗耐药机制为MET改变，MET扩增发生于5%-23%的EGFR耐药mCRC，并且随着后续治疗线数的增加，其发生率逐渐升高。Amivantamab是一种具有免疫细胞导向活性的EGFR-MET双特异性抗体，已获FDA批准用于EGFR突变晚期非小细胞肺癌的4项适应症。在1b/2期OrigAMI-1研究（NCT05379595）中，amivantamab联合FOLFIRI在既往未接受过抗EGFR治疗的RAS/BRAF WT mCRC参与者（pts）中显示出令人鼓舞的抗肿瘤活性，且与治疗线数无关（Pietrantonio ESMO 2024）。这项3期随机研究的目的是评估amivantamab联合FOLFIRI与cetuximab或bevacizumab联合FOLFIRI作为复发性RAS/BRAF WT mCRC患者二线治疗的疗效。 方法：全球性OrigAMI-3研究（NCT06750094）计划在25个国家的230个站点开展。符合条件的患者将为KRAS、NRAS和BRAF野生型，患有复发不可切除或mCRC，且必须在针对转移性疾病的一线全身治疗中出现疾病进展（既往方案必须为以氟嘧啶为基础和以奥沙利铂为基础的治疗）。允许纳入经过治疗、稳定且无症状的脑转移患者。主要排除标准包括既往未接受免疫治疗的已知dMMR/MSI-H状态、HER2阳性或扩增肿瘤，以及既往接受过伊立替康或靶向EGFR或MET的药物。约700例患者将按1:1随机分配接受皮下注射amivantamab（与重组人透明质酸酶[rHuPH20]共同配制）联合FOLFIRI，或静脉注射cetuximab或bevacizumab（由研究者根据当地指南选择）联合FOLFIRI。随机化将按cetuximab或bevacizumab的选择、原发肿瘤部位（左侧vs右侧）、一线治疗持续时间（<6个月或≥6个月）以及既往抗VEGF治疗（是或否）进行分层。双主要终点为盲态独立中心审查评估的无进展生存期和总生存期。次要终点包括客观缓解率、缓解持续时间和患者报告结局。安全性评估将包括监测不良事件和实验室异常。
查看英文原文 English abstract
Background: Among patients with metastatic colorectal cancer (mCRC), approximately 50% are wild-type for KRAS , NRAS , and BRAF ( RAS/BRAF WT) without actionable genomic alterations. Standard first-line therapy for RAS/ B RAF WT mCRC is 5-FU-based doublet chemotherapy (FOLFOX or FOLFIRI) plus anti-EGFR or anti-VEGF therapy. The choice of second-line treatment is dependent on first-line treatment (eg, oxaliplatin-based chemotherapy in the first-line necessitates irinotecan-based in the second-line, and vice versa). Known resistance mechanisms to anti-EGFR therapy are MET alterations, with MET amplification occurring in 5%-23% of EGFR-resistant mCRC and increasing in prevalence over subsequent lines of therapy. Amivantamab is an EGFR-MET bispecific antibody with immune cell-directing activity and is FDA-approved for 4 indications in EGFR -mutated advanced non-small cell lung cancer. In the phase 1b/2 OrigAMI-1 study (NCT05379595), amivantamab plus FOLFIRI demonstrated promising antitumor activity, independent of line of therapy, in participants (pts) with RAS / BRAF WT mCRC without prior anti-EGFR exposure (Pietrantonio ESMO 2024). The objective of this phase 3 randomized study is to assess the efficacy of amivantamab plus FOLFIRI vs cetuximab or bevacizumab plus FOLFIRI, as second-line therapy for pts with recurrent RAS / BRAF WT mCRC. Methods: The global OrigAMI-3 study (NCT06750094) is planned to open in 230 sites in 25 countries. Eligible pts will be WT for KRAS , NRAS , and BRAF , have recurrent unresectable or mCRC, and must have had disease progression on one prior line of systemic therapy for metastatic disease (prior regimen must be fluoropyrimidine-based and oxaliplatin-based therapy). Pts with treated, stable, and asymptomatic brain metastases are allowed. Key exclusion criteria include known dMMR/MSI-H status without prior immunotherapy, HER2-positive or amplified tumor, and prior exposure to irinotecan or agents targeting EGFR or MET. Approximately 700 pts will be randomly assigned 1:1 to receive subcutaneous amivantamab (co-formulated with recombinant human hyaluronidase [rHuPH20]) plus FOLFIRI vs intravenous cetuximab or bevacizumab (investigator's choice, per local guidelines) plus FOLFIRI. Randomization will be stratified by choice of cetuximab or bevacizumab, primary tumor location (left vs right-sided), duration of first-line therapy (<6 months or ≥6 months), and prior anti-VEGF therapy (yes or no). The dual primary endpoints will be progression-free survival by blinded independent central review and overall survival. Secondary endpoints include objective response rate, duration of response, and patient-reported outcomes. Safety assessments will include monitoring adverse events and laboratory abnormalities.
利益披露 Disclosure
J. Hecht, Astellas, Bristol Myers Squibb, Taiho Pharmaceutical, BeiGene, IGM Biosciences, Novartis, Galvanize, Exelixis, and Deciphera Other, consulting fees. Scripps, American Gastroenterological Association, MJH Life Sciences, and Research to Practice Other, consulting fees. Triumvira, Actym, and MBQ Pharma Stock. E. Élez, Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cureteq AG, Janssen, Lilly, Medscape, Merck, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Pierre Fabre, Repare Therapeutics Other, honoraria. RIN Institute, Roche, Sanofi-Aventis, Seagen, Servier, and Takeda Other, honoraria. Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cureteq AG, Janssen, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Pierre Fabre, Repare Therapeutics, RIN Institute, Roche, Sanofi-Aventis Other, consulting or advisory role. Seagen, Servier, and Takeda Other, consulting or advisory role. AbbVie, Amgen, Array BioPharma, AstraZeneca, Bayer, BeiGene, Bioncotech, BioNTech RNA Pharmaceuticals GMBH, BioNTech Small Molecules GMBH, Boehringer Ingelheim, Boehringer Ingelheim Spain ). Bristol Myers Squibb, Celgene, Daiichi Sankyo, Debiopharm, Genentech, Gercor, HalioDX SAS, Roche, Hutchison MediPharma, Iovance Biotherapeutics, Janssen Research & Development, Janssen-Cilag SA ). MedImmune, Menarini, Merck, Merck Sharp & Dohme (Spain) ). Merus NV, Mirati Therapeutics, Nouscom SRL, Novartis, Novartis Farmacéutica SA, Pfizer, PharmaMar, Pierre Fabre, PledPharma, Redx Pharma, Roche, Sanofi, Scandion Oncology, Seagen, Servier, Sotio, Tai ). Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cureteq AG, Janssen, Lilly, Medscape, Merck, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Pierre Fabre, Repare Therapeutics Travel. RIN Institute, Roche, Sanofi, Seagen, Servier, and Takeda Travel. C. Eng, Elevar Therapeutics (institution), Elevation Oncology, General Electric, GSK, Gritstone bio (institution), Hutchison MediPharma (institution), Janssen Oncology, Merck (institution), Merck Serono Other, consulting or advisory role. Natera, Pfizer (institution), and Seagen Other, consulting or advisory role. P. Gibbs, Amgen, Merck, MSD Oncology, Roche, SERVIER Other, honoraria. Amgen, Bayer, BMS, Sanofi, Merck Serono, Pierre Fabre, Roche, Roche Molecular Diagnostics, Servier, Takeda ). Haystack Oncology Other, consulting or advisory. J. Seligmann, GlaxoSmithKline, Merck Serono, Pierre Fabre, SERVIER, Takeda Science Foundation Other, honoraria. Elevation Oncology, GlaxoSmithKline, Jazz Pharma, Merck Serono, Sanofi, Takeda Other, Consulting or Advisory. GlaxoSmithKline, Merck Serono, Pierre Fabre ). R. Xu, Astellas, AstraZeneca, BeiGene, CPPC, Hengrui Pharm, Hutchison MediPharma, Innovent Biologics, Junshi Pharma, Keymed Bioscience, Merck Serono, MSD, QiLu Pharma, Roche Other, Consulting or advisory. K. Yamaguchi, BMS Japan, Daiichi Sankyo Other, Consulting or advisory. Ono Pharma, Taiho Pharma, Daiichi Sankyo, Lilly, Gilead Sciences, Yakult Honsha, Chugai Pharma, Boehringer Ingelheim, Eisai, MSD Oncology, Sanofi, BMS ). Chugai Pharma, BMS Japan, Takeda, Taiho Pharma, Lilly, Ono Pharma, Daiichi Sankyo, Merck Other, Speakers Bureau. J. Wang, None. H. Teng, MSD Other, Consulting or Advisory, Speakers Bureau. Merck Sharp & Dohme LLC ). L. Trani, Johnson & Johnson Employment, Stock. H. Wortman-Vayn, Johnson & Johnson Employment, Stock. Z. Jiang, Johnson & Johnson Employment, Stock. B. Diorio, Johnson & Johnson Employment, Stock. P. Lorenzini, Johnson & Johnson Employment, Stock. C. Baudelet, Johnson & Johnson Employment, Stock. S. Sethi, Johnson & Johnson Employment, Stock. M. Baig, Johnson & Johnson Employment, Stock. C. Cremolini, Roche, Amgen, Bayer, Servier, MSD, Merck, Pierre Fabre Other, Honoraria. Roche, Bayer, Amgen, MSD, Pierre Fabre, Nordic Bioscience Other, Consulting or advisory. Servier, Merck, Pierre Fabre Other, Speakers Bureau. Merck, Bayer, Roche, Servier ).

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