Subcutaneous versus intravenous pembrolizumab, in combination with chemotherapy, for treatment of metastatic non-small-cell lung cancer: the phase III 3475A-D77 trial.

The phase III open-label 3475A-D77 study (NCT05722015) assessed s.c. pembrolizumab versus intravenous (i.v.) pembrolizumab, plus chemotherapy, for treatment of metastatic non-small-cell lung cancer (mNSCLC).

III期开放标签的3475A-D77研究（NCT05722015）评估了皮下注射（s.c.）的pembrolizumab与静脉注射（i.v.）的pembrolizumab，加上化疗，用于治疗转移性非小细胞肺癌（mNSCLC）。

patients_and_methods

Participants with newly diagnosed stage IV squamous or nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 alterations were randomized 2 : 1 to pembrolizumab s.c. 790 mg every 6 weeks (q6w) or pembrolizumab i.v. 400 mg q6w (18 cycles), each given with platinum-doublet chemotherapy.

新诊断的IV期鳞状或非鳞状非小细胞肺癌（NSCLC）患者，且无敏感性EGFR、ALK或ROS1改变，按2:1比例随机分配至每6周皮下注射790毫克帕博利珠单抗（q6w）或每6周静脉注射400毫克帕博利珠单抗（共18个周期），两种方案均与铂类双药化疗联合使用。

Dual primary endpoints were pharmacokinetic exposure measures of cycle 1 area under the curve (AUC0-6 weeks) and steady-state trough concentration (Ctrough) of pembrolizumab.

主要终点是第1周期药物暴露量的药代动力学测量，包括6周内的曲线下面积（AUC0-6周）和稳态谷浓度（Ctrough）的帕博利珠单抗。

The noninferiority margin for AUC0-6 weeks and Ctrough geometric mean ratios (GMRs) of pembrolizumab s.c. versus i.v. was specified as 0.8.

AUC0-6周和Pembrolizumab皮下注射与静脉注射的C最小值几何平均比率（GMRs）的非劣效性边界被设定为0.8。

Secondary endpoints included additional pharmacokinetic exposure measures, pembrolizumab immunogenicity, efficacy, and safety.

次要终点包括额外的药物动力学暴露量度量，Pembrolizumab的免疫原性，疗效和安全性。

Results

In total 377 participants were randomized to the pembrolizumab s.c.

共有377名参与者被随机分配到pembrolizumab皮下注射组。

(n = 251) or i.v.

(n = 251)或静脉注射组。

(n = 126) arms.

(n = 126)组别。

The median time from randomization to data cut-off (12 July 2024) was 9.6 months (range 6.2-16.4 months).

从随机分组到数据截止（2024年7月12日）的中位时间是9.6个月（范围6.2-16.4个月）。

The median injection time for pembrolizumab s.c. was 2.0 min (range 1-12 min).

帕博利珠单抗皮下注射的中位注射时间是2.0分钟（范围1-12分钟）。

The GMR [96% confidence interval(CI)] for cycle 1 AUC0-6 weeks was 1.14 (1.06-1.22); P < 0.0001.

第1周期0-6周的AUC几何均数比（GMR）为1.14（96%置信区间1.06-1.22）；P < 0.0001。

The GMR (94% CI) for steady-state Ctrough was 1.67 (1.52-1.84); P < 0.0001.

稳态时 Ctrough 的几何均数比率（94% 置信区间）为 1.67（1.52-1.84）；P < 0.0001。

Secondary pharmacokinetic endpoints were within established bounds for pembrolizumab.

次要药代动力学终点在为 pembrolizumab 建立的界限内。

Anti-pembrolizumab antibodies were detected in 1.4% (pembrolizumab s.c. arm) and 0.9% (pembrolizumab i.v. arm) of participants.

在1.4%的参与者（pembrolizumab皮下注射组）和0.9%的参与者（pembrolizumab静脉注射组）中检测到了抗pembrolizumab抗体。

For the pembrolizumab s.c. versus i.v. arms, objective response rates (ORRs) were 45.4% versus 42.1% (ORR ratio 1.08, 95% CI 0.85-1.37).

对于pembrolizumab皮下注射组与静脉注射组，客观缓解率（ORR）分别为45.4%和42.1%（ORR比值为1.08，95%置信区间为0.85-1.37）。

Other efficacy measures were similar and safety profiles were consistent between treatment arms.

其他疗效指标在各治疗组之间相似，安全性特征也保持一致。

Conclusions

Overall exposure and trough concentrations of pembrolizumab s.c. 790 mg q6w were noninferior to those of pembrolizumab i.v. 400 mg q6w given with chemotherapy in participants with treatment-naive mNSCLC.

在治疗未接受过治疗的mNSCLC患者中，每6周皮下注射790毫克帕博利珠单抗的总体暴露量和谷浓度不劣于每6周静脉注射400毫克帕博利珠单抗联合化疗。

Results support pembrolizumab s.c. as a treatment option in all indications where pembrolizumab i.v. can be used.

结果支持将pembrolizumab s.c.作为pembrolizumab i.v.可以使用的所有适应症的治疗选择。