INTERLINK-1：一项关于莫纳利珠单抗联合西妥昔单抗治疗复发/转移性头颈部鳞状细胞癌的III期随机安慰剂对照研究。
INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma.
作者信息
Fayette Jérôme, Licitra Lisa, Harrington Kevin, Haddad Robert, Siu Lillian L, Liu Yi-Chun, Tahara Makoto, Machiels Jean-Pascal, Rischin Danny, Seiwert Tanguy Y, Ferris Robert L, Keilholz Ulrich, Psyrri Amanda, Keam Bhumsuk, Bossi Paolo, Metcalf Robert, Hsieh Ching-Yun, Clement Paul M J, Isaev Pavel, Mudunov Ali, Dinis José, Hoeben Ann, Kasper Stefan, Klinghammer Konrad, Hwang Michael, Blando Jorge, Serrano Olivier, Ruscica Dario, Cohen Roger B
机构信息
Centre de Lutte Contre le Cancer Léon Bérard, Lyon-I University, Lyon, France.
Fondazione IRCCS Instituto Nazionale dei Tumori and University of Milan, Milan, Italy.
出版信息
Clin Cancer Res. 2025 Jul 1;31(13):2617-2627. doi: 10.1158/1078-0432.CCR-25-0073.
PURPOSE
Treatment options for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) after failure of immune checkpoint inhibitor treatment and platinum-based chemotherapy are limited. Preliminary data suggested that monalizumab plus cetuximab had clinical activity in R/M HNSCC.
PATIENTS AND METHODS
INTERLINK-1 (NCT04590963) was a double-blind, phase III study. Participants with R/M HNSCC who had received immune checkpoint inhibitor therapy and progressed despite platinum-based chemotherapy were randomized 2:1 to monalizumab (750 mg, every 2 weeks) or placebo, plus cetuximab (400 mg/m2 loading dose, then 250 mg/m2, weekly). The primary endpoint was overall survival (OS) in participants with non-oropharyngeal cancer or human papillomavirus (HPV)-negative oropharyngeal cancer (HPV-unrelated analysis set). Secondary endpoints included progression-free survival and objective response rate.
RESULTS
At data cutoff, 216 participants were randomized in the HPV-unrelated analysis set: 145 to monalizumab plus cetuximab and 71 to placebo plus cetuximab. Median OS was 8.8 months for monalizumab plus cetuximab versus 8.6 months for placebo plus cetuximab (HR, 1.00; 95% confidence interval, 0.66-1.54); median progression-free survival was 3.6 versus 3.8 months, respectively (HR, 1.11; 95% confidence interval, 0.79-1.57); and the objective response rate was 15.2% versus 23.9%, respectively. INTERLINK-1 was terminated after a preplanned interim analysis showed that futility criteria were met (predetermined futility HR >0.874). Grade 3/4 treatment-related adverse events were reported in 18.3% and 17.2% of participants treated in the monalizumab and placebo arms, respectively.
CONCLUSIONS
Monalizumab plus cetuximab did not improve OS compared with placebo plus cetuximab. The safety profile of the combination was consistent with safety observations for cetuximab monotherapy.
目的
免疫检查点抑制剂治疗和铂类化疗失败后的复发/转移性（R/M）头颈部鳞状细胞癌（HNSCC）的治疗选择有限。初步数据表明，莫纳利珠单抗联合西妥昔单抗在R/M HNSCC中具有临床活性。
患者和方法
INTERLINK-1（NCT04590963）是一项双盲III期研究。接受过免疫检查点抑制剂治疗且尽管接受了铂类化疗仍进展的R/M HNSCC患者按2:1随机分组，分别接受莫纳利珠单抗（750 mg，每2周一次）或安慰剂，加西妥昔单抗（400 mg/m²负荷剂量，然后250 mg/m²，每周一次）。主要终点是患有非口咽癌或人乳头瘤病毒（HPV）阴性口咽癌患者的总生存期（OS）（HPV无关分析集）。次要终点包括无进展生存期和客观缓解率。
结果
在数据截止时，216名参与者被随机纳入HPV无关分析集：145名接受莫纳利珠单抗联合西妥昔单抗治疗，71名接受安慰剂联合西妥昔单抗治疗。莫纳利珠单抗联合西妥昔单抗组的中位OS为8.8个月，安慰剂联合西妥昔单抗组为8.6个月（HR，1.00；95%置信区间，0.66 - 1.54）；中位无进展生存期分别为3.6个月和3.8个月（HR，1.11；95%置信区间，0.79 - 1.57）；客观缓解率分别为15.2%和23.9%。在一项预先计划的中期分析显示达到无效标准（预定无效HR>0.874）后，INTERLINK-1研究终止。在莫纳利珠单抗组和安慰剂组接受治疗的参与者中，分别有18.3%和17.2%报告了3/4级治疗相关不良事件。
结论
与安慰剂联合西妥昔单抗相比，莫纳利珠单抗联合西妥昔单抗并未改善OS。联合治疗的安全性与西妥昔单抗单药治疗的安全性观察结果一致。
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