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INTERLINK-1: A phase III, randomized, placebo-controlled study of monalizumab plus cetuximab in recurrent/metastatic head and neck squamous cell carcinoma

Fayette, J.
; 
Licitra, L.
; 
Harrington, K.
; 
Haddad, R.
; 
Siu, L. L.
; 
Liu, Y. C.
; 
Tahara, M.
; 
Machiels, J. P.
; 
Rischin, D.
; 
Seiwert, T. Y.
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Abstract
PURPOSE: Treatment options for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) after failure of immune checkpoint inhibitor treatment and platinum-based chemotherapy are limited. Preliminary data suggested that monalizumab plus cetuximab had clinical activity in R/M HNSCC. PATIENTS AND METHODS: INTERLINK-1 (NCT04590963) was a double-blind, phase III study. Participants with R/M HNSCC who had received immune checkpoint inhibitor therapy and progressed despite platinum-based chemotherapy were randomized 2:1 to monalizumab (750 mg, every 2 weeks) or placebo, plus cetuximab (400 mg/m2 loading dose, then 250 mg/m2, weekly). The primary endpoint was overall survival (OS) in participants with non-oropharyngeal cancer or human papillomavirus (HPV)-negative oropharyngeal cancer (HPV-unrelated analysis set). Secondary endpoints included progression-free survival and objective response rate. RESULTS: At data cutoff, 216 participants were randomized in the HPV-unrelated analysis set: 145 to monalizumab plus cetuximab and 71 to placebo plus cetuximab. Median OS was 8.8 months for monalizumab plus cetuximab versus 8.6 months for placebo plus cetuximab (HR, 1.00; 95% confidence interval, 0.66-1.54); median progression-free survival was 3.6 versus 3.8 months, respectively (HR, 1.11; 95% confidence interval, 0.79-1.57); and the objective response rate was 15.2% versus 23.9%, respectively. INTERLINK-1 was terminated after a preplanned interim analysis showed that futility criteria were met (predetermined futility HR >0.874). Grade 3/4 treatment-related adverse events were reported in 18.3% and 17.2% of participants treated in the monalizumab and placebo arms, respectively. CONCLUSIONS: Monalizumab plus cetuximab did not improve OS compared with placebo plus cetuximab. The safety profile of the combination was consistent with safety observations for cetuximab monotherapy.
Authors
Fayette, J.
Licitra, L.
Harrington, K.
Haddad, R.
Siu, L. L.
Liu, Y. C.
Tahara, M.
Machiels, J. P.
Rischin, D.
Seiwert, T. Y.
Ferris, R. L.
Keilholz, U.
Psyrri, A.
Keam, B.
Bossi, P.
Metcalf, R.
Hsieh, C. Y.
Clement, P. M. J.
Isaev, P.
Mudunov, A.
Dinis, J.
Hoeben, A.
Kasper, S.
Klinghammer, K.
Hwang, M.
Blando, J.
Serrano, O.
Ruscica, D.
Cohen, R. B.
Affiliation
Centre de Lutte Contre le Cancer Léon Bérard, Lyon-I University, Lyon, France. Fondazione IRCCS Instituto Nazionale dei Tumori and University of Milan, Milan, Italy. The Royal Marsden/The Institute of Cancer Research NIHR Biomedical Research Centre, London, United Kingdom. Dana-Farber Cancer Institute, Boston, Massachusetts. Princess Margaret Cancer Centre, Toronto, Canada. Taichung Veterans General Hospital, Taichung, Taiwan. National Cancer Center Hospital East, Kashiwa, Japan. Institut Roi Albert II, Cliniques Universitaires Saint-Luc and Institute for Experimental and Clinical Research (IREC, pôle MIRO), Université Catholique de Louvain, Brussels, Belgium. Peter MacCallum Cancer Centre, Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia. Johns Hopkins University, Baltimore, Maryland. UNC Lineberger Comprehensive Cancer Center and UNC Health System, Chapel Hill, North Carolina. Charité Comprehensive Cancer Center, Berlin, Germany. Attikon University Hospital, National Kapodistrian University of Athens, Athens, Greece. Seoul National University Hospital, Seoul, Republic of Korea. Humanitas University, Milan, Italy. IRCCS Humanitas Research Hospital, Milan, Italy. The Christie NHS Foundation Trust, Manchester, United Kingdom. China Medical University Hospital, Taichung City, Taiwan. Department of General Medical Oncology, Leuven Cancer Institute, KU Leuven, UZ Leuven, Leuven, Belgium. National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation. Clinical Hospital 'Lapino,' Moscow, Russian Federation. Instituto Português de Oncologia do Porto Francisco Gentil, Porto, Portugal. GROW- School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands. West German Cancer Center, University Hospital, Essen, Germany. Oncology and Tumor Immunology, Charité Comprehensive Cancer Center, Berlin, Germany. AstraZeneca, South San Francisco, California. AstraZeneca, Gaithersburg, Maryland. Cytel Inc., AstraZeneca, Paris, France. AstraZeneca, Cambridge, United Kingdom. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
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2025
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Fayette J, Licitra L, Harrington K, Haddad R, Siu LL, Liu YC, et al. INTERLINK-1: A phase III, randomized, placebo-controlled study of monalizumab plus cetuximab in recurrent/metastatic head and neck squamous cell carcinoma. Clinical cancer research: an official journal of the American Association for Cancer Research. 2025 Jul 1;31(13):2617-27.
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https://christie.openrepository.com/handle/10541/627845
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