Galot Rachel, Le Tourneau Christophe, Saada-Bouzid Esma, Daste Amaury, Even Caroline, Debruyne Philip, Henry Stéphanie, Zanetta Sylvie, Rutten Anemie, Licitra Lisa, Canon Jean-Luc, Kaminsky Marie-Christine, Specenier Pol, Rottey Sylvie, Guigay Joël, Kong Anthony, Tinhofer Inge, Borcoman Edith, Dirix Lieve, Raveloarivahy Tiana, Fortpied Catherine, Vanlancker Maureen, Morfouace Marie, Govaerts Anne-Sophie, Machiels Jean-Pascal
Service d'Oncologie Médicale, Institut Roi Albert II, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, 1200 Brussels, Belgium.
Department of Drug Development and Innovation, Institut Curie, Paris, Saint-Cloud, France; INSERM U900 Research Unit, Saint-Cloud, France; Versailles-Saint-Quentin-en-Yvelines University, Montigny-le-Bretonneux, France.
Eur J Cancer. 2021 Oct 9;158:17-26. doi: 10.1016/j.ejca.2021.09.003.
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.
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.
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%).
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.
莫纳利珠单抗是一种单克隆抗体，靶向定位于自然杀伤（NK）细胞和T细胞上的抑制性自然杀伤细胞2A（NKG2A）受体。其配体人类白细胞抗原E（HLA-E）在头颈部鳞状细胞癌（SCCHN）中过表达。通过靶向HLA-E-NKG2A通路，莫纳利珠单抗可能增强NK细胞和T细胞活性。
UPSTREAM试验是一项由生物标志物驱动的伞形试验，研究铂类治疗后进展的复发/转移性（R/M）SCCHN患者的靶向治疗和免疫治疗。免疫治疗1（I1）队列是一项II期单臂子研究，评估莫纳利珠单抗（在14天周期的第1天静脉注射10mg/kg）。主要终点是前16周的客观缓解（OR）率（实体瘤疗效评价标准1.1）。采用两阶段西蒙设计（H1 15%，H0 3%，α 8%，检验效能90%），如果在前25例患者中未观察到OR，则预先计划中断入组。
纳入26例符合条件的患者。17例（65%）患者既往接受过≥2线全身治疗，15例（58%）患者接受过PD（-L）1抑制剂预处理。未观察到OR。6例（23%）患者病情稳定，中位持续时间为3.8个月（95%置信区间[CI]：2.7-未达到）。中位无进展生存期和总生存期分别为1.7个月（95%CI：1.5-1.8）和6.7个月（95%CI：3.0-9.6）。最常见的治疗相关不良事件为I/II级疲劳（19%）。
莫纳利珠单抗单药治疗在R/M SCCHN中的活性有限。I1队列未达到其主要目标。莫纳利珠单抗联合度伐利尤单抗正在UPSTREAM试验中进行研究。
