KEY TAKEAWAYS
- INTERLINK-1 is a Phase 3 global study evaluating the efficacy and safety of monalizumab + cetuximab in pts with recurrent/metastatic HNSCC.
- Eligible pts must have measurable R/M HNSCC, be previously treated with CT and a PD-(L)1 inhibitor, and have an ECOG performance status of 0 or 1.
- The primary objective is (OS) in human papillomavirus-unrelated pts. In contrast, key secondary objectives include OS in all randomized pts and PFS.
- The study is currently ongoing at 210 sites in 25 countries.
With an expected 930,000 new cases and 470,000 deaths in 2020, head and neck (HN) cancer is the seventh most common and seventh leading cause of cancer death worldwide. HN squamous cell carcinoma (HNSCC) accounts for around 90% of HN cancers. Patients with R/M HNSCC have two treatment options: immune checkpoint inhibitor (ICI) therapy with single-agent pembrolizumab (anti-programmed cell death-1) or + CT and 5-fluorouracil (5- FU) or cetuximab (anti-epidermal growth factor receptor) in combination with (+) platinum-based chemotherapy (CT) and 5-fluorouracil (5- FU). Single-agent cetuximab, immune checkpoint inhibitor ICI pembrolizumab, or ICI nivolumab may be administered to 3-5 Pts who progress on or after CT. 3 Rechallenge is not indicated. Therapy for patients progressing during or after ICI is not well-defined. Combination immunotherapy techniques must therefore be evaluated. Patients with R/M HNSCC who had previously had CT and an ICI demonstrated promising antitumor responses to monalizumab (anti-NKG2A) + cetuximab combination therapy in Phase 2 research. 6 Patients with R/M HNSCC who have already been treated with CT and an ICI will be eligible to participate in INTERLINK-1 (NCT04590963), a global Phase 3 research assessing the effectiveness and safety of monalizumab + cetuximab.
The study will enroll about 624 patients and randomly assign them to receive either monalizumab plus cetuximab or placebo plus cetuximab until disease progression or another discontinuation criterion is reached. After treatment is stopped, all patients will be monitored to see if they survive. Patients who meet the inclusion criteria will have stage IV head and neck squamous cell carcinoma (HNSCC) in the oral cavity, oropharynx, hypopharynx, or larynx that has progressed on prior CT and is not susceptible to curative therapy. Patients must have an ECOG performance status of 0 or 1, give a fresh/recently acquired tumor sample, and have previously been treated with a PD-(L)1 inhibitor for R/M HNSCC. Essential contraindications include a history of adverse reactions to cetuximab for R/M HNSCC, the presence of an autoimmune/inflammatory condition, or the use of any other anticancer drugs. The primary endpoint is OS in patients without known association with human papillomavirus. Secondary goals focused on pharmacokinetics, safety, tolerability, overall survival in all randomized patients, objective response rate, duration of response, disease-related symptoms, functioning, quality of life, and pharmacodynamics. At present, participants are being enrolled in 210 sites throughout 25 nations.
Source: https://aacrjournals.org/cancerres/article/82/12_Supplement/CT236/702746/Abstract-CT236-INTERLINK-1-A-phase-3-randomized
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04590963
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. https://doi.org/10.1158/1538-7445.AM2022-CT236
