INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma.
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Embargo End Date
ICR Authors
Authors
Fayette, J
Licitra, L
Harrington, K
Haddad, R
Siu, LL
Liu, Y-C
Tahara, M
Machiels, J-P
Rischin, D
Seiwert, TY
Ferris, RL
Keilholz, U
Psyrri, A
Keam, B
Bossi, P
Metcalf, R
Hsieh, C-Y
Clement, PMJ
Isaev, P
Mudunov, A
Dinis, J
Hoeben, A
Kasper, S
Klinghammer, K
Hwang, M
Blando, J
Serrano, O
Ruscica, D
Cohen, RB
INTERLINK-1 investigators,
Licitra, L
Harrington, K
Haddad, R
Siu, LL
Liu, Y-C
Tahara, M
Machiels, J-P
Rischin, D
Seiwert, TY
Ferris, RL
Keilholz, U
Psyrri, A
Keam, B
Bossi, P
Metcalf, R
Hsieh, C-Y
Clement, PMJ
Isaev, P
Mudunov, A
Dinis, J
Hoeben, A
Kasper, S
Klinghammer, K
Hwang, M
Blando, J
Serrano, O
Ruscica, D
Cohen, RB
INTERLINK-1 investigators,
Document Type
Journal Article
Date
2025-07-01
Date Accepted
2025-04-23
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.
Citation
Clinical Cancer Research, 2025, pp. OF1 - OF11
Source Title
Clinical Cancer Research
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
1078-0432
eISSN
1557-3265
Collections
Research Team
Targeted Therapy