INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma.

Preliminary data suggested that monalizumab plus cetuximab had clinical activity in R/M HNSCC.

初步数据表明，monalizumab联合cetuximab在复发/转移性（R/M）头颈部鳞状细胞癌（HNSCC）中具有临床活性。

patients_and_methods

INTERLINK-1 (NCT04590963) was a double-blind, phase III study.

INTERLINK-1 (NCT04590963) 是一项双盲、III期研究。

Participants with R/M HNSCC who had received immune checkpoint inhibitortherapy 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).

参与研究的R/M HNSCC患者曾接受过免疫检查点抑制剂治疗，并在铂类化疗后疾病进展，这些患者按2:1的比例随机接受monalizumab（每两周750毫克）或安慰剂治疗，同时联合使用cetuximab（首剂400 mg/m2，随后每周250 mg/m2）。

The primary endpoint was overall survival(OS) in participants with non-oropharyngeal cancer or human papillomavirus (HPV)-negative oropharyngeal cancer (HPV-unrelated analysis set).

主要终点是参与者的总生存期（OS），研究对象为非口咽癌患者或人乳头瘤病毒（HPV）阴性的口咽癌患者（HPV无关分析集）。

Secondary endpoints included progression-free survivaland objective response rate.

次要终点包括无进展生存期和客观缓解率。

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.

在数据截止时，216名参与者被随机分配到HPV无关分析集：145名接受monalizumab联合cetuximab治疗，71名接受安慰剂联合cetuximab治疗。

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 survivalwas 3.6 versus 3.8 months, respectively (HR, 1.11; 95% confidence interval, 0.79-1.57); and the objective response ratewas 15.2% versus 23.9%, respectively.

中位总生存期为8.8个月，monalizumab联合cetuximab治疗组对比安慰剂联合cetuximab治疗组为8.6个月（风险比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%。

INTERLINK-1 was terminated after a preplanned interim analysis showed that futility criteria were met (predetermined futility HR >0.874).

INTERLINK-1 在预先计划的中期分析后被终止，因为满足了无效标准（预定的无效风险比>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.

在接受monalizumab和安慰剂治疗的参与者中，分别报告了18.3%和17.2%的3/4级治疗相关不良事件。

Conclusions

Monalizumab plus cetuximab did not improve OS compared with placebo plus cetuximab.

Monalizumab 联合 cetuximab 并未改善总生存期，与安慰剂联合 cetuximab 相比。

The safety profile of the combination was consistent with safety observations for cetuximab monotherapy.

联合用药的安全性特征与 cetuximab 单药治疗的安全性观察结果一致。