INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

作者：Jérôme Fayette, Lisa Francesca Licitra, Kevin Joseph Harrington, Robert I. Haddad, Lillian L. Siu, Yi‐Chun Liu, Makoto Tahara, Jean‐Pascal Machiels, Danny Rischin, Tanguy Y. Seiwert, Robert Louis Ferris, Ulrich Keilholz, Amanda K. Psyrri, Bhumsuk Keam, Paolo Bossi, Robert L. Metcalf, Ching-Yun Hsieh, Paul M. Clément, P. A. Isaev, Ali Muradovich Mudunov, José Dinis, Ann Hoeben, Stefan Kasper, Konrad Friedrich Klinghammer, Michael S. Hwang, Jorge M. Blando, Olivier Serrano, Dario Ruscica, Roger B. Cohen, for the INTERLINK-1 investigators, Douglas R. Adkins, Lúcia Águas, Myung‐Ju Ahn, Yolanda Escobar Álvarez, Jessica Ruth Bauman, Maureen Bernadach, Federica Bertolini, Marcelo Raul Bonomi, Christian Borel, Paolo Bossi, Michael Joseph Boyer, Santiago Cabezas Camarero, Tsung-Ming Chen, Wonyoung Choi, Vyacheslav A. Chubenko, Paul Clement, Roger B. Cohen, Anirudha Dasgupta, Amaury Daste, Helena Rebelo‐de‐Andrade, Jan Paul de Boer, Thiago Bueno de Oliveira, Charles AJ de Padua, Jan H. Demol, João Marcos Domingues Dias, Andreas Dietz, José Dinis, Lara Carmen Iglesias Docampo, Lucas Vieira dos Santos, Khashayar Esfahani, Agustin Horacio Falco, Jérôme Fayette, Chistian Sebastian Fuentes, Madoka Kaneko Furukawa, Danilo Galizia, Hui Kong Gan, Irene Braña Garcia, Maria Ghi, Robert I. Haddad, Simon Häfliger, Kevin Joseph Harrington, Stéphanie Henry, Ann Hoeben, Yoshitaka Honma, Ching-Yun Hsieh, Pavel A. Isaev, Philipp Ivanyi, Demetria I. Jacks, Alfonso Berrocal Jaime, Michael J. Jelinek, Ana Vieira Joaquim, Ricklie Ann Julian, Michalis V. Karamouzis, Stefan Kasper, Bhumsuk Keam, Charles Kelly, Sung‐Bae Kim, Ji‐Won Kim, Hee Kyung Kim, Naomi Kiyota, Konrad Friedrich Klinghammer, Светлана Игоревна Кутукова, Simon A. Laban, Rubi K. Li, Lisa Francesca Licitra, Jin-Ching Lin, Yi‐Chun Liu, Lorenzo Livi, Sílvia Lopes, Jean‐Pascal Machiels, Milena Perez Mak, Muneyuki Masuda, Thibault Mazard, Robert Lewin Metcalf, Brandon Matthew Meyers, Aurora Mirabile, Ali Muradovich Mudunov, Urs D. A. Müller-Richter, Prakash C. Neupane, Grzegorz S. Obara, Obiageli Uchenna Ogbata, Kenji Okami, Nobuhiko Oridate, Konstantinos Papazizis, Martín Paskevicius, Dainik Patel, Konstantin Penkov, Francesco Paolo Perri, Petar Petrov, Zia Poonja, Marshall R. Posner, Rafaela Pozzobon, Katharine Andress Rowe Price, Amanda K. Psyrri, J. Marruecos Querol, Justyna K. Rawluk, Danny Rischin, Sacha I. Rothschild, Paweł Różanowski, Rossitza Krasteva Ruseva, Sébastien Salas, Seong Hoon Shin, Hitesh B. Singh, Lillian L. Siu, Martin Smoragiewicz, Paul Loren Swiecicki, Petr Szturz, Masahiro Tabata, Makoto Tahara, Shunji Takahashi, Kaoru Tanaka, Margarida Teixeira, Clémence Toullec, Petranka P. Troyanova, Tsutomu Ueda, Charles Uy, Carla ML van Herpen, Marek Z. Wojtukiewicz, Muh‐Hwa Yang, Cheng Tzu Yen, Chia‐Jui Yen, Tomoya Yokota, Dan Paul Zandberg, Sylvie Zanetta, Bogdan A. Żurawski · 发表于：Clinical Cancer Research · 年份：2025 · DOI：10.1158/1078-0432.ccr-25-0073 · 被引用次数：27 · 研究领域：Head and Neck Cancer Studies、Cancer Immunotherapy and Biomarkers、Viral-associated cancers and disorders

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 futil...