A phase II study of monalizumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: The I1 cohort of the EORTC-HNCG-1559 UPSTREAM trial

Rachel Galot, Christophe Le Tourneau, Esma Saada-Bouzid, Amaury Daste, Caroline Even, Philip Debruyne, Stéphanie Henry, Sylvie Zanetta, Anemie Rutten, Lisa Licitra, Jean Luc Canon, Marie Christine Kaminsky, Pol Specenier, Sylvie Rottey, Joël Guigay, Anthony Kong, Inge Tinhofer, Edith Borcoman, Lieve Dirix, Tiana RaveloarivahyCatherine Fortpied, Maureen Vanlancker, Marie Morfouace, Anne Sophie Govaerts, Jean Pascal Machiels*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Purpose: Monalizumab is a monoclonal antibody targeting the inhibitory natural killer group 2A (NKG2A) receptor localised on natural killer (NK) and T cells. Its ligand, the human leukocyte antigen E (HLA-E), is overexpressed in squamous cell carcinoma of the head and neck (SCCHN). By targeting the HLA-E-NKG2A pathway, monalizumab may enhance NK and T cell activity. Experimental design: The UPSTREAM trial is a biomarker-driven umbrella trial studying targeted therapies and immunotherapies in patients with recurrent/metastatic (R/M) SCCHN progressing after platinum therapy. The immunotherapy 1 (I1) cohort was a phase II, single-arm substudy evaluating monalizumab (10 mg/kg intravenously on day 1 of a 14-day cycle). The primary end-point was the objective response (OR) rate (Response Evaluation Criteria in Solid Tumours 1.1) over the first 16 weeks. A two-stage Simon design was used (H1 15%, H0 3%, α 8%, power 90%) with pre-planned interruption of accrual if no OR was observed after the first 25 patients. Results: Twenty-six eligible patients were enrolled. Seventeen (65%) patients had received ≥2 previous lines of systemic treatment, and 15 (58%) patients were PD(-L)1 inhibitor pretreated. No OR was observed. Stable disease was observed in 6 patients (23%) with a median duration of 3.8 months (95% confidence interval [CI]: 2.7–NE). The median progression-free survival and overall survival were 1.7 months (95% CI: 1.5–1.8) and 6.7 months (95% CI: 3.0–9.6), respectively. The most frequent treatment-related adverse event was grade I/II fatigue (19%). Conclusions: Monalizumab monotherapy has limited activity in R/M SCCHN. The I1 cohort did not meet its primary objective. Monalizumab combined with durvalumab is under investigation within UPSTREAM.

Original languageEnglish
Pages (from-to)17-26
Number of pages10
JournalEuropean Journal of Cancer
Volume158
Early online date9 Oct 2021
DOIs
Publication statusPublished - Nov 2021

Keywords

  • Immunotherapy
  • NKG2A
  • Precision medicine
  • Squamous cell carcinoma of the head and neck
  • Umbrella trial

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