NCI9673 (Part B): ETCTN Randomized Phase II Study of Nivolumab With or Without Ipilimumab in Refractory, Metastatic Squamous Cell Carcinoma of the Anal Canal.

In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer.

在NCI9673（B部分）中，我们评估了抗细胞毒性T细胞淋巴细胞抗原-4（CTLA-4）抗体伊匹木单抗与纳武单抗联合用于治疗无法治愈的肛门癌患者。

Methods

In this phase II NCI ETCTN trial, 100 patients with refractory, incurable anal cancer were randomly assigned to receive nivolumab (480 mg IV once every 4 weeks) alone or with ipilimumab (1 mg/kg IV once every 8 weeks).

在这项NCI ETCTN的II期试验中，100名难治性、无法治愈的肛门癌患者被随机分配接受纳武单抗（每4周静脉注射480毫克）单独治疗或与伊匹木单抗（每8周静脉注射1毫克/公斤）联合治疗。

The primary end point was progression-free survival(PFS).

主要终点是无进展生存（PFS）。

Secondary endpoints included radiographic response, overall survival(OS), and grade ≥3 adverse events.

次要终点包括影像学反应、总生存（OS）和3级或以上不良事件。

A log-rank test was used to compare survival between arms, with a one-sided alpha of 0.1 and power of 90%.

使用了Log-rank检验来比较各组之间的生存情况，检验水准为单侧0.1，功效为90%。

Immune biomarkers were analyzed from baseline and on treatment tissue and blood collections.

从基线和治疗期间的组织和血液样本中分析了免疫生物标志物。

Results

The median PFS for nivolumab versus nivolumab plus ipilimumab were 2.9 months (90% CI, 1.9 to 3.8) and 3.7 months (90% CI, 2.0 to 5.6), respectively (hazard ratio[HR], 0.86 [95% CI, 0.60 to 1.23]; P = .25).

纳武利尤单抗与纳武利尤单抗联合伊匹木单抗的中位无进展生存期分别为2.9个月（90%置信区间，1.9至3.8个月）和3.7个月（90%置信区间，2.0至5.6个月），风险比为0.86（95%置信区间，0.60至1.23；P = .25）。

Response rates were similar for nivolumab (17.4%) and nivolumab plus ipilimumab (21.5%; P = .89).

尼伏单抗的反应率(17.4%)与尼伏单抗联合伊匹木单抗的反应率(21.5%; P = .89)相似。

The median OS was 15.9 months for nivolumab and 20.0 months for nivolumab plus ipilimumab (HR, 0.98 [90% CI, 0.63 to 1.51]).

尼伏单抗的中位总生存期为15.9个月，而尼伏单抗联合伊匹木单抗的中位总生存期为20.0个月（HR, 0.98 [90% 置信区间, 0.63 至 1.51]）。

Grade ≥3 treatment-related AEs occurred in 6 patients (12%) receiving nivolumab alone and in 12 patients (25%) receiving nivolumab plus ipilimumab.

仅接受纳武单抗治疗的患者中有6名（12%）出现了3级或更高级别的治疗相关不良事件，而接受纳武单抗联合伊匹木单抗治疗的患者中有12名（25%）出现了3级或更高级别的治疗相关不良事件。

At week 9, circulating TIGIT+ CD8+ cells (P < .001) increased with nivolumab plus ipilimumab treatment relative to baseline.

在第9周时，与基线相比，接受纳武单抗联合伊匹木单抗治疗的患者循环中的TIGIT+ CD8+细胞（P < .001）有所增加。

Conclusions

The addition of ipilimumab to nivolumab did not statistically improve overall response rate, PFS, or OS but may harbor increased toxicity.

将伊匹木单抗加入纳武单抗并未在统计学上显著改善总体反应率、无进展生存期或总生存期，但可能带来更高的毒性。

Paired blood samples identified TIGIT expression on peripheral T cells as a compensatory change unique to dual PD-1 plus CTLA-4 blockade.

配对的血液样本揭示了外周T细胞上TIGIT表达作为双重PD-1和CTLA-4阻断所特有的代偿性改变。