Standard-of-care for resectable gastric/gastroesophageal junction cancer includes surgery and neoadjuvant-adjuvant 5-fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) chemotherapy. Early-phase clinical studies support further clinical development of the immune checkpoint inhibitor (ICI); durvalumab, an anti-PD-L1 antibody, in patients with gastric/gastroesophageal junction cancer. Accumulating evidence indicates that ICIs combined with FLOT chemotherapy improve clinical outcomes in patients with advanced or metastatic cancer. We describe the rationale for and the design of MATTERHORN, a randomized, double-blind, placebo-controlled, phase III study investigating the efficacy and safety of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy followed by adjuvant durvalumab monotherapy in patients with resectable gastric/gastroesophageal junction cancer. The planned sample size is 900 patients, the primary end point is event-free survival and safety and tolerability will be evaluated. Clinical trial registration: NCT04592913 (ClinicalTrials.gov.
Bibliographical noteFunding Information:
This study is sponsored by AstraZeneca. Y Janjigian has stock or ownership interest in RGENIX; has a consulting or advisory role with AstraZeneca, Basilea Pharmaceutica, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Imugene, Merck Serono, Merck, Michael J. Hennessy Associates, Paradigm Medical Communications, Pfizer, RGENIX, Seagen and Zymeworks Inc.; and has received research funding from Bayer, Bristol Myers Squibb, Cycle for Survival, Department of Defense, Eli Lilly, Fred’s Team, Genentech/Roche, Merck, NCI and RGENIX. E Van Cutsem has received research funding from Amgen (Inst), Bayer (Inst), Boehringer Ingelheim (Inst), Lilly (Inst), Merck Serono (Inst), Novartis (Inst), Roche (Inst), and Sanofi (Inst). K Muro has received personal fees from AstraZeneca during the conduct of the study; grants from Solasia Pharma, Merck Serono, Daiichi Sankyo, Parexel International, Pfizer, and MSD; grants and personal fees from Amgen, Ono, Sanofi, Taiho, and AstraZeneca; and personal fees from Chugai, Takeda, Eli Lilly, Bristol Myers Squibb and Bayer, outside the submitted work. Z Wainberg has served as a consultant or an advisor for Array BioPharma, AstraZeneca/MedImmune, Bayer, Bristol Myers Squibb, Five Prime Therapeutics, Genentech, Lilly, Merck, Merck KGaA, and Novartis; has received research funding from Five Prime Therapeutics (Inst), Merck (Inst), Novartis (Inst), Pfizer (Inst), Plexxikon (Inst); and has received travel, accommodations and expenses from Genentech. S Al-Batran has served as an advisor for Lilly, Bristol Myers Squibb, MacroGenics, Immutep, and MSD Sharp & Dohme; as a speaker for Bristol Myers Squibb, Lilly, AIO Studien gGmbH, and MCI Deutschland GmbH; and as CEO/founder of the Institute of Clinical Cancer Research IKF at Northwest Hospital; and has received research grants from Sanofi, Roche, Celgene, Vifor, Medac, Hospira, Lilly, Eurozyto, Immutep, Ipsen, Bristol Myers Squibb, MSD Sharp & Dohme, AstraZeneca, German Cancer Aid (Krebshilfe), German Research Foundation, and the Federal Ministry of Education and Research. WJ Hyung is an employee in a leadership role and shareholder of Hutom; has served as a consultant or advisor for with Ethicon; and has received research funding from Medtronic and GC Pharma. D Molena reports participation on a steering committee with AstraZeneca, during the conduct of the study; and has received other travel reimbursement from Intuitive and consultant fees from UroGen, Johnson & Johnson, and Boston Scientific, outside the submitted work. M Marcovitz, D Ruscica, SH Robbins and A Negro are employees and shareholders of AstraZeneca. J Tabernero reports personal financial interest in form of scientific consultancy role for 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, NeoPhore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Scandion Oncology, Servier, Taiho, Tessa Therapeutics, and TheraMyc; educational collaboration with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource (PER); and institutional financial interest in the form of financial support for clinical trials or contracted research for 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-Cilag SA, MedImmune, Menarini, Merck Health KGaA, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc, Spanish Association Against Cancer Scientific Foundation, and Cancer Research UK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Medical writing support, under the guidance of the authors, was provided by C Tinderholm, of CMC Connect, McCann Health Medical Communications (UK), and was funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines (Ann. Intern. Med. 163, 461–464 ).
© 2022 The Authors.
All Science Journal Classification (ASJC) codes
- Cancer Research