INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
Jérôme Fayette, Lisa Licitra, Kevin J. Harrington, Robert I. Haddad, Lillian L. Siu, Yi‐Chun Liu, Makoto Tahara, Jean‐Pascal Machiels, Danny Rischin, Tanguy Y. Seiwert, Robert L. Ferris, Ulrich Keilholz, Amanda Psyrri, Bhumsuk Keam, Paolo Bossi, Robert L. Metcalf, Ching-Yun Hsieh, Paul M. Clément, P. A. Isaev, А. М. Мудунов, José Dinis, Ann Hoeben, Stefan Kasper, Konrad Klinghammer, Michael S. Hwang, Jorge 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 R. Bauman, Maureen Bernadach, Federica Bertolini, Marcelo Bonomi, Christian Borel, Paolo Bossi, Michael Boyer, Santiago Cabezas Camarero, Tsung-Ming Chen, Wonyoung Choi, Vyacheslav Chubenko, Paul Clement, Roger B. Cohen, Anirudha Dasgupta, Amaury Daste, Helena Rebelo‐de‐Andrade, Jan Paul de Boer, Thiago Bueno de Oliveira, Charles Padua, Jan Demol, João Marcos Domingues Dias, Andreas Dietz, José Dinis, Lara Carmen Iglesias Docampo, Lucas Vieira dos Santos, Khashayar Esfahani, Agustín Falco, Jérôme Fayette, Chistian Sebastian Fuentes, Madoka Furukawa, Danilo Galizia, Hui Gan, Irene García, Maria Ghi, Robert I. Haddad, Simon Häfliger, Kevin J. Harrington, Stéphanie Henry, Ann Hoeben, Yoshitaka Honma, Ching-Yun Hsieh, П. А. Исаев, Philipp Ivanyi, Demetria I. Jacks, Alfonso Berrocal Jaime, Michael J. Jelinek, Ana Joaquim, Ricklie Julian, Michalis V. Karamouzis, Stefan Kasper, Bhumsuk Keam, Charles Kelly, Sung‐Bae Kim, Ji‐Won Kim, Hee Kyung Kim, Naomi Kiyota, Konrad Klinghammer, С. И. Кутукова, Simon Laban, Rubi K. Li, Lisa Licitra, Jin-Ching Lin, Yi‐Chun Liu, Lorenzo Livi, Sílvia Lopes, Jean‐Pascal Machiels
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.