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

Fayette, J; INTERLINK-1 investigators; Licitra, L; Harrington, K; Haddad, R; Siu, LL; Liu, YC; Tahara, M; Machiels, JP; Rischin, D; Seiwert, TY; Ferris, RL; Keilholz, U; Psyrri, A; Keam, B; Bossi, P; Metcalf, R; Hsieh, CY; Clement, PMJ; Isaev, P; Mudunov, A; Dinis, J; Hoeben, A; Kasper, S; Klinghammer, K; Hwang, M; Blando, J; Serrano, O; Ruscica, D; Cohen, RB

Author(s): Fayette, J; INTERLINK-1 investigators; Licitra, L; Harrington, K; Haddad, R; Siu, LL; Liu, YC; Tahara, M; Machiels, JP; Rischin, D; Seiwert, TY; Ferris, RL; Keilholz, U; Psyrri, A; Keam, B; Bossi, P; Metcalf, R; Hsieh, CY; Clement, PMJ; Isaev, P; Mudunov, A; Dinis, J; Hoeben, A; Kasper, S; Klinghammer, K; Hwang, M; Blando, J; Serrano, O; Ruscica, D; Cohen, RB;
Details: Publication Year 2025-07-01,Volume 31,Issue #13,Page 2617-2627
Journal Title: Clinical Cancer Research
Publication Type: Research article
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.
Publisher: American Association for Cancer Research
Keywords: Adult; Aged; Female; Humans; Male; Middle Aged; *Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects; *Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse; effects; *Cetuximab/administration & dosage/adverse effects; Double-Blind Method; *Head and Neck Neoplasms/drug therapy/pathology/mortality; *Neoplasm Recurrence, Local/drug therapy/mortality/pathology; *Squamous Cell Carcinoma of Head and Neck/drug; therapy/mortality/pathology/secondary
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1158/1078-0432.Ccr-25-0073
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.Ccr-25-0073
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-06-02 01:58:40

Last Modified: 2025-07-22 07:47:55