Galot R, Le Tourneau C, Licitra L, Guigay J, Kong A, Tinhofer I, Even C, Daste A, Henry S, Borel C, Abdeddaim C, Seront E, Prevost J B, Rutten A, Saada-Bouzid E, Rolland F, Bonomo P, Rasschaert M, Dirix L, Olungu C, Tsechilidou K, Govaerts A S, Fortpied C, Joaquim A, Machiels J P
Service d'Oncologie Médicale and Institut de Recherche Clinique et Expérimentale, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Department of Drug Development and Innovation, Institut Curie, Paris & Saint-Cloud, France; INSERM U900 Research Unit, Saint-Cloud, France; Université de Paris-Saclay, Paris, France.
ESMO Open. 2025 Apr 30;10(5):104554. doi: 10.1016/j.esmoop.2025.104554.
Monalizumab (M), targeting the natural killer group 2A (NKG2A) receptor, has limited activity as monotherapy in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). Preliminary data of M and durvalumab (D) have shown encouraging activity in other tumor types.
The UPSTREAM trial was an umbrella trial of targeted therapies and immunotherapy for R/M SCCHN. The immunotherapy 2 (I2) cohort was a phase II, randomized, open-label substudy evaluating the efficacy of D + M versus physician's choice (control). Patients non-eligible for the biomarker-driven cohorts and pretreated with PD(L)1, were included in the I2 cohort. The primary endpoint was the objective response rate (RECIST version 1.1) during the first 16 weeks.
Sixty-six patients with R/M SCCHN were included in the I2 cohort, of whom 60 were assessable (D + M: n = 42, control: n = 18): median age 62 years; 87% with two or three previous lines of treatment. In the D + M arm, one partial response (PR) was recorded, and stable disease (SD) was observed in 11 (26%). One PR was reported in the control arm and SD in 8 (44%). The median progression-free survival (PFS) was 2.0 and 3.1 months in the D + M arm and control arm, respectively. The median overall survival (OS) was 4.3 months (95% confidence interval 3.3-8.9 months) and 8.0 months (95% confidence interval 3.1-14.9 months) in the D + M and control arms, respectively. In the D + M arm, 4 (9%) patients reported grade ≥3 treatment-related adverse events.
The I2 substudy failed to demonstrate an activity of D + M in heavily pretreated patients with SCCHN previously exposed to anti-PD(L)1. No benefit was seen in PFS and OS.
莫纳利珠单抗（M）靶向自然杀伤细胞2A（NKG2A）受体，作为单药疗法治疗复发/转移性（R/M）头颈部鳞状细胞癌（SCCHN）时活性有限。莫纳利珠单抗与度伐利尤单抗（D）的初步数据显示在其他肿瘤类型中具有令人鼓舞的活性。
UPSTREAM试验是一项针对R/M SCCHN的靶向治疗和免疫治疗的伞形试验。免疫治疗2（I2）队列是一项II期、随机、开放标签的子研究，评估D + M与医生选择（对照）的疗效。不符合生物标志物驱动队列标准且接受过PD（L）1预处理的患者被纳入I2队列。主要终点是前16周的客观缓解率（RECIST 1.1版）。
I2队列纳入了66例R/M SCCHN患者，其中60例可评估（D + M组：n = 42，对照组：n = 18）：中位年龄62岁；87%接受过两或三线先前治疗。在D + M组，记录到1例部分缓解（PR），11例（26%）观察到疾病稳定（SD）。对照组报告1例PR，8例（44%）为SD。D + M组和对照组的中位无进展生存期（PFS）分别为2.0个月和3.1个月。D + M组和对照组的中位总生存期（OS）分别为4.3个月（95%置信区间3.3 - 8.9个月）和8.0个月（95%置信区间3.1 - 14.9个月）。在D + M组，4例（9%）患者报告了≥3级治疗相关不良事件。
I2子研究未能证明D + M在先前接受过抗PD（L）1治疗的SCCHN重度预处理患者中的活性。在PFS和OS方面未观察到获益。
