Abstract CT236: INTERLINK-1: A phase 3, randomized, double-blind, placebo-controlled, multicenter, global study of monalizumab in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma previously treated with an immune checkpoint inhibitor
Authors: Fayette Jérôme , Seiwert Tanguy , Ferris Robert L. , Harrington Kevin , Haddad Robert , Tahara Makoto , Licitra Lisa , Siu Lillian L. , Machiels Jean-Pascal , Dominiewska Malgorzata , Xiong Julia , Kaur Paramjit , Ruscica Dario , Cohen Roger B. 
Published: June 2022

Abstract
Background: Head and neck (HN) cancer is the 7th most common cancer and 7th leading cause of cancer death worldwide with approximately 930,000 new cases and 470,000 deaths in 2020.1 HN squamous cell carcinoma (HNSCC) accounts for around 90% of HN cancers.2 Options for first-line treatment of patients (pts) with recurrent/metastatic (R/M) HNSCC include cetuximab (anti-epidermal growth factor receptor) in combination with (+) platinum-based chemotherapy (CT) and 5-fluorouracil (5- FU), or immune checkpoint inhibitor (ICI) therapy with single-agent pembrolizumab (anti-programmed cell death-1) or + CT and 5-FU.3-5 Pts who progress on/after CT may receive single-agent cetuximab, ICI pembrolizumab, or ICI nivolumab.3 However, treatment for pts who progress on/after ICI is not clearly defined and rechallenge is not recommended. Thus, there is a need to assess combination immunotherapy approaches. In a Phase 2 study, monalizumab (anti-NKG2A) + cetuximab combination therapy showed encouraging antitumor results in pts with R/M HNSCC who received prior CT and an ICI.6 INTERLINK-1 (NCT04590963) is a Phase 3 global study evaluating the efficacy and safety of monalizumab + cetuximab in pts with R/M HNSCC previously treated with CT and an ICI.
Methods: Approximately 624 pts will be randomized 2:1 to monalizumab + cetuximab or placebo + cetuximab until disease progression or another discontinuation criterion is met. All pts will be followed for survival after discontinuation. Eligible pts will have measurable R/M HNSCC (per RECIST v1.1) of the oral cavity, oropharynx, hypopharynx or larynx, which is not amenable to curative therapy and has progressed on/after previous CT. They will have received 1-2 prior systemic regimens for R/M HNSCC, had prior treatment with a PD-(L)1 inhibitor, an ECOG performance status of 0 or 1, and must provide a fresh/recently acquired tumor sample. Key exclusion criteria include prior cetuximab therapy for R/M HNSCC, autoimmune/inflammatory disease or any concurrent anticancer treatment. The primary objective is overall survival (OS) in human papillomavirus-unrelated pts. Key secondary objectives include OS in all randomized pts, progression-free survival, objective response rate, duration of response, disease-related symptoms, functioning and quality of life, pharmacokinetics, safety and tolerability. Study enrollment is ongoing at 210 sites in 25 countries.
References: 1. Sung et al. CA Cancer J Clin 2021; 71: 209-49 2. UICC. Head and Neck Cancer. 2014. who.int 3. NCCN®. Head and Neck Cancers. 2021. nccn.org/guidelines 4. Machiels et al. Ann Oncol 2020; 31: 1462-75 5. Keam et al. ESMO Open 2021; 6: 100309 6. Cohen et al. J Clin Oncol 2020; 38 (15 suppl): Abst 6516.
Study Sponsor: AstraZeneca.
Citation Format: Jérôme Fayette, Tanguy Seiwert, Robert L. Ferris, Kevin Harrington, Robert Haddad, Makoto Tahara, Lisa Licitra, Lillian L. Siu, Jean-Pascal Machiels, Malgorzata Dominiewska, Julia Xiong, Paramjit Kaur, Dario Ruscica, Roger B. Cohen. INTERLINK-1: A phase 3, randomized, double-blind, placebo-controlled, multicenter, global study of monalizumab in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma previously treated with an immune checkpoint inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT236.