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

Galot, Rachel and Le Tourneau, Christophe and Saada-Bouzid, Esma and Daste, Amaury and Even, Caroline and Debruyne, Philip R. and Henry, Stéphanie and Zanetta, Sylvie and Rutten, Anemie and Licitra, Lisa and Canon, Jean-Luc and Kaminsky, Marie-Christine and Specenier, Pol and Rottey, Sylvie and Guigay, Joël and Kong, Anthony and Tinhofer, Inge and Borcoman, Edith and Dirix, Lieve and Raveloarivahy, Tiana and Fortpied, Catherine and Vanlancker, Maureen and Morfouace, Marie and Govaerts, Anne-Sophie and Machiels, Jean-Pascal (2021) 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. European Journal of Cancer Care, 158. pp. 17-26. ISSN 1365-2354

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Official URL: https://doi.org/10.1016/j.ejca.2021.09.003

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.

Item Type: Journal Article
Keywords: Squamous cell carcinoma of the head and neck, Immunotherapy, NKG2A, Precision medicine, Umbrella trial
Faculty: Faculty of Health, Education, Medicine & Social Care
Depositing User: Lisa Blanshard
Date Deposited: 28 Oct 2021 11:43
Last Modified: 28 Oct 2021 11:43
URI: https://arro.anglia.ac.uk/id/eprint/707055

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