PO.CTP01.03 · 进行中的临床试验

OrigAMI-2: A randomized, phase 3 study of amivantamab vs cetuximab, both in combination with FOLFOX or FOLFIRI, as first-line treatment in left-sided RAS / BRAF wild-type metastatic colorectal cancer

编号 CT217 展板 12 🕑 4/21 09:00–12:00 📍 Section 51 主讲 Bing Xia

分会场 Phase II and Phase III Clinical Trials in Progress

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作者与单位 Authors & Affiliations

Dirk Arnold¹, Andres Cervantes², Michel Ducreux³, Sae-won Han⁴, Heinz-Josef Lenz⁵, Kei Muro⁶, Kanwal Raghav⁷, Lin Shen⁸, Jaw Yuan Wang⁹, Pei Jye Voon¹⁰, Hung-Chuh Hsu¹¹, Bing Xia¹², Ryota Iwasawa¹³, Shamita Carrigan¹³, Brooke Diorio¹⁴, Patricia Lorenzini¹⁴, Sandip Acharya¹⁵, Seema Sethi¹³, Mahadi Baig¹⁴, Filippo Pietrantonio¹⁶

¹Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg, Germany,²INCLIVA University of Valencia, Valencia, Spain,³Université Paris-Saclay, Department of Medical Oncology, Gustave Roussy, Inserm Unité Dynamique des Cellules Tumorales, Villejuif, France,⁴Seoul National University Hospital, Seoul, Korea, Republic of,⁵USC Norris Comprehensive Cancer Center, Los Angeles, CA,⁶Aichi Cancer Center Hospital, Nagoya, Japan,⁷MD Anderson Cancer Center, Houston, TX,⁸Beijing Cancer Hospital, Beijing, China,⁹Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan,¹⁰Department of Radiotherapy and Oncology, Sarawak General Hospital, Kuching, Sarawak, Malaysia,¹¹College of Medicine, Chang Gung University, Taoyuan, and Division of Hematology-Oncology Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan,¹²Johnson & Johnson, San Diego, CA,¹³Johnson & Johnson, Spring House, PA,¹⁴Johnson & Johnson, Raritan, NJ,¹⁵Johnson & Johnson, Hyderabad, India,¹⁶Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

摘要 Abstract

Background: Approximately 50% of patients diagnosed with metastatic colorectal cancer (mCRC) are wild-type for KRAS , NRAS , and BRAF ( RAS/BRAF WT). Standard initial therapy for left-sided RAS/BRAF WT mCRC is doublet chemotherapy (FOLFOX or FOLFIRI) combined with anti-EGFR therapy. However, resistance is nearly inevitable. MET alterations are known resistance mechanisms to EGFR inhibition, with MET amplification occurring in 5%-23% of EGFR-resistant mCRC. Amivantamab is an EGFR-MET bispecific antibody with immune cell-directing activity that is approved by the FDA for 4 indications in EGFR -mutated advanced non-small cell lung cancer. In the phase 1b/2 OrigAMI-1 study (NCT05379595), the combination of amivantamab plus FOLFOX or FOLFIRI demonstrated rapid and durable antitumor activity, regardless of tumor sidedness, in participants with RAS / BRAF WT mCRC (Pietrantonio ESMO 2024). The objective of this phase 3 randomized study is to assess the efficacy of amivantamab, as compared with cetuximab, both in combination with FOLFOX or FOLFIRI, as first-line therapy for participants with left-sided RAS / BRAF WT unresectable or metastatic CRC. Methods: The multicenter, global OrigAMI-2 study (NCT06662786) is planned to open in 216 sites in 21 countries. Eligible participants will be WT for KRAS , NRAS , and BRAF by local testing, have left-sided unresectable or metastatic colorectal cancer, and be treatment-naïve for advanced disease. Left-sided disease will be defined as a primary tumor arising from the splenic flexure, descending colon, sigmoid colon, rectosigmoid, or rectum. Key exclusion criteria include known dMMR/MSI-H status, HER2-positive or amplified tumor, and prior exposure to EGFR or MET targeting agents. Approximately 1000 participants will be randomly assigned 1:1 to receive subcutaneous amivantamab (co-formulated with recombinant human hyaluronidase [rHuPH20]) or intravenous cetuximab, both combined with FOLFOX or FOLFIRI (investigator's choice). Randomization will be stratified by chemotherapy choice (FOLFOX or FOLFIRI), limited disease (yes or no), and prior adjuvant therapy (yes or no). The primary endpoint will be progression-free survival by blinded independent central review. Secondary endpoints include overall survival, 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

D. Arnold, Amgen, Aptitude Health, Art Tempi Media, AstraZeneca, Boehringer Ingelheim, Boston Scientific, Clinical Care Options, Eisai, Research to Practice, GSK, Imedex, iOMEDICO (Germany), Ipsen, MCI Other, invited speaker. Merck Serono, PeerMD (China), PRMA Consulting, Sanofi (Genzyme), Servier, Sirtex, Streamitup Germany, Tactics MD LLC, Viatris, and WebMD Health Corp Other, invited speaker. Amgen, AstraZeneca, Boston Scientific, Bristol Myers Squibb, CRA International, Gilead, Janssen-Cilag, Merck Sharp & Dohme, Onkowissen, Pierre Fabre Other, advisory board. Seagen, Takeda, and Terumo Other, advisory board. AbbVie (institution) ). OncoLytics, Phanes Therapeutics, AIO (German Cancer Society), ASCO, DGHO, EORTC, and ESO Other, other non-financial interests. Elsevier and Sanofi (Genzyme) Other, other relationships. A. Cervantes, Amgen, Foundation Medicine, Merck Serano, Roche, Transgene Other, advisory role. Actuate Therapeutics, Adaptimmune, Amcure, Amgen, Astellas Pharma, AstraZeneca Spain, Beyer, BeiGene, BMSi, FibroGen, Genentech, Lilly, MedImmune, Merck Serono, MSD, Natera, Novartis, SERVIER ). Sierra Oncology, Takeda ). M. Ducreux, Sandoz Employment. Bayer, Pierre Fabre, Roche/Genentech, TERUMO Other, honoraria. Abbvie, Abcely, Amgen, Astellas, AstraZeneca, Basilea, Bayer, Daiichi Sankyo/AstraZeneca, GlaxoSmithKline, HalioDx, Ipsen, Lilly, Merck Serono, MSD, Novartis, Pierre Fabre, Rafael Pharma, Roche Other, Consulting or Advisory Role. Scandion Oncology, Servier, Sotio, Zymeworks Other, Consulting or Advisory Role. Amgen, AstraZeneca, Bayer, GalxoSmithKline, HalioDx, Lilly, Merck KGaA, MSD, Pierre Fabre, Roche, SERVIER Other, Speakers Bureau. Keocyt, Roche ). S. Han, AstraZeneca, Natera, and AbbVie Other, consulting or advisory role. Boryung, IMBdx, Hanmi, Loxo Oncology, Roche, Genentech, Mirati Therapeutics, Arcus Biosciences, Merck Sharp & Dohme, BeyondBio, Jeil Pharmaceutical, Janssen, Seagen, Lilly, MedImmune ), research funding (all to institution). Leap Therapeutics, Jiangsu Hengrui Pharmaceutical, GC Biopharma, AbbVie, Cell Biotech, Astellas, Merck, GSK, and AstraZeneca ), research funding (all to institution). H. Lenz, Bayer, Boehringer Ingelheim, Fulgent Genetics, G1 Therapeutics, Isofol Medical, Jazz Pharmaceuticals, Merck Serono, Oncocyte, Roche Other, Honoraria. 3T BioSciences, Bayer, BMS, Fulgent Genetics, GlaxoSmithKline, Merck Serono, Roche Other, Consulting or Advisory Role. K. Muro, Bayer, BMS, Chugai Pharma, Daiichi Sankyo/UCB Japan, Lilly, Ono Pharmaceutical, Sanofi, Taiho Pharmaceutical, Takeda Other, Honoraria. Amgen, AstraZeneca, Chugai Pharma, Ono Pharmaceutical, Soasia Pharma Other, Consulting to Advisory Role. Amgen, Astellas, Chugai Pharma, Daiichi Sankyo, Eisai, Merck KGaA, MSD, Novartis, Ono Pharmaceutical, Pfizer, Sanofi, Taiho Pharmaceutical ). K. Raghav, AstraZeneca, Bayer, Eisai, Daiichi Sankyo, and Seagen Other, consulting or advisory role. Bayer Other, speakers bureau. Bayer (institution), Roche/Genentech (institution), Guardant Health (institution), Daiichi Sankyo/AstraZeneca (institution), HiberCell (institution), and Merck Serono (institution) ). L. Shen, AstraZeneca, Boehringer Ingelheim, MSD, SERVIER, Transcenta Holding Limited Other, Consulting or Advisory Role. BeiGene ). J. Wang, None. P. Voon, AstraZeneca, Novartis, Boehringer Ingelheim, Janssen-Cilag, Johnson & Johnson, Viracta Therapeutics, Inc., Roche, Merck KGaA, Merck Sharp & Dohme, BeiGene, Amgen, and Revolution Medicines Other, received grants or contracts. AstraZeneca, Novartis, Merck Sharp & Dohme, Pfizer, BeiGene, Amgen, Merck KGaA, Janssen-Cilag, and Johnson & Johnson Other, consulting fees. AstraZeneca, Novartis, Merck Sharp & Dohme, Pfizer, Amgen, Merck KGaA, Janssen-Cilag, and Johnson & Johnson Other, received payment or honoraria. H. Hsu, None. B. Xia, Johnson & Johnson Employment, Stock. R. Iwasawa, Johnson & Johnson Employment, Stock. S. Carrigan, Johnson & Johnson Employment, Stock. B. Diorio, Johnson & Johnson Employment, Stock. P. Lorenzini, Johnson & Johnson Employment, Stock. S. Acharya, Johnson & Johnson Employment, Stock. S. Sethi, Johnson & Johnson Employment, Stock. M. Baig, Johnson & Johnson Employment, Stock. F. Pietrantonio, Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Daiichi Sankyo, Incyte, Ipsen, Johnson & Johnson, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Seagen, Servier, and Takeda Other, honoraria as an invited speaker. Agenus, Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Daiichi Sankyo, Gilead, GSK, Incyte, Italfarmaco SpA, Jazz Pharmaceuticals, Johnson & Johnson, Merck Sharp & Dohme Other, consulting or advisory role. Merck Serono, Pfizer, Pierre Fabre, Revolution Medicines, Rottapharm Biotech, Servier, and Takeda Other, consulting or advisory role. Agenus, Amgen, AstraZeneca, Bristol Myers Squibb, GSK, Incyte, Johnson & Johnson, Lilly, and Rottapharm Biotech ), research funding (to Institution).

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