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Title
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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
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Author
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Abstract
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| 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%, a 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. (c) 2021 Elsevier Ltd. All rights reserved. |
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Language
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English
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Source (journal)
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European journal of cancer. - Oxford, 1990, currens
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Publication
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Oxford
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2021
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ISSN
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0959-8049
[print]
1879-0852
[online]
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DOI
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10.1016/J.EJCA.2021.09.003
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Volume/pages
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158
(2021)
, p. 17-26
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ISI
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000708670200004
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Pubmed ID
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34638090
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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