Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B).

Methods

Eligible patients with advanced-stage EGFR exon20ins NSCLC were randomly assigned by 1:1 ratio to receive sunvozertinib 200 mg or 300 mg once daily (200 and 300 mg-rand cohorts).

符合条件的晚期 EGFR exon20ins NSCLC 患者按照 1:1 的比例随机分配接受每日一次 200 mg 或 300 mg 的 sunvozertinib (200 和 300 mg-rand 队列)。

After predefined interim analysis, additional patients were enrolled and treated with the 300 mg dose once daily.

在预先设定的中期分析后，额外的患者被纳入并接受每日一次300 mg剂量的治疗。

The primary end point was blinded independent review committee (IRC)-assessed confirmed objective response rate(cORR), and the key secondary end point was duration of response (DoR).

主要终点是盲法独立审查委员会（IRC）评估的确认客观缓解率（cORR），而关键的次要终点是缓解持续时间（DoR）。

Results

Among 85, 89, and 107 efficacy-evaluable patients in 200 mg-rand, 300 mg-rand, and 300 mg-all (including randomly assigned and nonrandomized patients) cohorts, the cORRs were 45.9% (97.5% CI, 33.6% to 58.5%), 47.2% (97.5% CI, 35.1% to 59.5%), and 45.8% (97.5% CI, 34.8% to 57.0%), respectively, per IRC assessment.

在200 mg-rand、300 mg-rand和300 mg-all（包括随机分配和非随机患者）队列中，分别有85、89和107名疗效可评估患者，IRC评估的cORR分别为45.9%（97.5% 置信区间，33.6%至58.5%）、47.2%（97.5% 置信区间，35.1%至59.5%）和45.8%（97.5% 置信区间，34.8%至57.0%）。

The predefined null hypothesis was rejected with statistical significance (P < .0001).

预设的零假设被统计学显著性拒绝（P < .0001）。

Comparing 300 and 200 mg-rand cohorts, higher cORRs were observed in patients with baseline brain metastasis (52.4% v 28.6%) and previous amivantamab treatment (41.7% v 25%), as well as longer DoR (13.8 v 11.1 months).

比较300 mg和200 mg-rand队列，基线时有脑转移的患者中观察到更高的cORRs（52.4%对比28.6%），以及之前接受过amivantamab治疗的患者（41.7%对比25%），以及更长的DoR（13.8个月对比11.1个月）。

At 200 and 300 mg once daily, the most common treatment-related adverse events with grade ≥3 included diarrhea (2.2% v 18%), blood creatine phosphokinase increased (6.6% v 12.6%), and anemia (4.4% v 6.3%).

在200 mg和300 mg每日一次的剂量下，最常见的与治疗相关的3级或更高级别的不良事件包括腹泻（2.2%对比18%），血肌酸磷酸激酶增加（6.6%对比12.6%），和贫血（4.4%对比6.3%）。

Conclusions

Sunvozertinib is efficacious at both 200 and 300 mg once daily in treating platinum-pretreated patients with advanced EGFR exon20ins NSCLC.

Sunvozertinib每日一次200毫克和300毫克在治疗接受过铂类药物预处理的晚期EGFR exon20ins突变非小细胞肺癌患者中均显示出疗效。

The treatment-related adverse events of sunvozertinib were consistent with an EGFR tyrosine kinase inhibitor, with a more favorable safety profile at 200 mg than 300 mg once daily.

Sunvozertinib相关的治疗不良事件与EGFR酪氨酸激酶抑制剂一致，每日一次200毫克的患者比300毫克的安全性更好。