INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab Plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
- Author(s)
- Fayette, J; 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;
- Journal Title
- Clinical Cancer Research
- Publication Type
- Online publication before print
- Abstract
- PURPOSE: Treatment options for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) after failure of immune checkpoint inhibitor (ICI) treatment and platinum-based chemotherapy are limited. Preliminary data suggested monalizumab plus cetuximab had clinical activity in R/M HNSCC. PARTICIPANTS AND METHODS: INTERLINK-1 (NCT04590963) was a double-blind, phase III study. Participants with R/M HNSCC who had received ICI therapy and progressed despite platinum-based chemotherapy were randomized 2:1 to monalizumab (750 mg, fortnightly) 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 (OPC) or human papillomavirus (HPV)-negative OPC (HPV-unrelated analysis set). Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). RESULTS: At data cut-off, 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 (hazard ratio [HR], 1.00; 95% CI, 0.66-1.54); median PFS was 3.6 versus 3.8 months, respectively (HR, 1.11; 95% CI, 0.79-1.57); and ORR was 15.2% versus 23.9%, respectively. INTERLINK-1 was terminated after a preplanned interim analysis showed 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.
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1158/1078-0432.Ccr-25-0073
- Open Access at Publisher's Site
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Creation Date: 2025-06-02 01:58:40
Last Modified: 2025-06-02 01:59:04