Final Analysis Results and Patient-Reported Outcomes From DESTINY-Lung02-A Dose-Blinded, Randomized, Phase 2 Study of Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic NSCLC.

This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes.

本次最终分析评估了在额外8个月随访后的T-DXd疗效和安全性，包括临床相关的亚组和患者报告的结果。

Methods

DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks.

DESTINY-Lung02 是一项随机、剂量盲法、多中心、II期临床试验。既往接受过治疗的 HER2 突变型晚期非小细胞肺癌患者按 2:1 的比例随机接受 T-DXd 5.4 或 6.4 mg/kg 每 3 周一次的治疗。

Primary end point was confirmed objective response rateby blinded independent central review.

主要终点是通过盲法独立中央审查确认的客观缓解率。

Results

As of August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively.

截至2023年8月25日，分别有102名和50名患者接受了T-DXd 5.4 mg/kg或6.4 mg/kg的治疗。

Median follow-up (Q1-Q3) was 15.8 (8.2-20.7) months and 16.5 (9.4-20.8) months, respectively.

中位随访时间（四分位数间距）分别为15.8（8.2-20.7）个月和16.5（9.4-20.8）个月。

Confirmed objective response rate(95% confidence interval) was 50.0% (51/102; 39.9%-60.1%) and 56.0% (28/50; 41.3%-70.0%), respectively.

确认的客观缓解率（95%置信区间）分别为50.0%（51/102；39.9%-60.1%）和56.0%（28/50；41.3%-70.0%）

Safety profile was acceptable and generally manageable.

安全性特征是可以接受的，并且通常是可管理的。

Accordingly, median treatment duration (Q1-Q3) was 7.7 (3.7-14.4) months and 8.3 (2.8-13.1) months; drug-related grade 3 or higher treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]).

因此，中位治疗持续时间（四分位数间距）为7.7（3.7-14.4）个月和8.3（2.8-13.1）个月；与药物相关的3级或更高级别的治疗相关不良事件发生率为39.6%（40/101）和60.0%（30/50），其中恶心最为常见（67.3% [68/101]，82.0% [41/50]）。

Adjudicated drug-related interstitial lung disease occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1 or 2 with one grade 5 in each arm.

经裁定的与药物相关的间质性肺病发生率为14.9%（15/101）和32.0%（16/50），大多数为1级或2级，每组各有1例5级。

Health-related quality of life was preserved for the duration of T-DXd treatment while sample size was sufficient for analysis, with no adverse effects on health-related quality of life observed at either dose.

在T-DXd治疗期间，健康相关生活质量得到了保持，样本量足以进行分析，无论剂量如何，均未观察到对健康相关生活质量的不良影响。

Conclusions

T-DXd demonstrated strong and durable responses at both doses, with no clinically significant changes in toxicity.

T-DXd在两种剂量下均显示出强烈且持久的反应，毒性方面没有出现临床上显著的变化。

The approved 5.4-mg/kg dose demonstrated a more favorable benefit-risk profile, including lower adjudicated drug-related interstitial lung disease incidence.

批准的5.4-mg/kg剂量显示出更有利的效益-风险比，包括较低的裁定药物相关间质性肺病发生率。

gov_identifier

NCT04644237.

NCT04644237