Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer (HARMONi-6): interim overall survival analysis of a randomised, double-blind, phase 3 trial in China.

In our previous report of the HARMONi-6 study, we aimed to evaluate the efficacy and safety of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as a first-line therapy for patients with advanced squamous NSCLC.

在我们之前关于HARMONi-6研究的报告中，我们旨在评估ivonescimab联合化疗与tislelizumab联合化疗作为晚期鳞状非小细胞肺癌患者一线治疗的疗效和安全性。

Ivonescimab combined with chemotherapy significantly prolonged progression-free survivalcompared with tislelizumab plus chemotherapy.

伊沃西米单抗联合化疗显著延长了无进展生存期，与替西利尤单抗联合化疗相比。

Here we report the prespecified interim overall survivalanalysis.

在此我们报告了预先设定的中期总生存分析。

Methods

HARMONi-6 is a double-blind, randomised, phase 3 trial, which was conducted at 50 hospitals across China.

HARMONi-6 是一项在中国50家医院进行的双盲、随机、III期试验。

Patients aged 18-75 years with previously untreated, pathologically confirmed, unresectable stage IIIB, IIIC, or stage IV squamous NSCLC and an Eastern Cooperative Oncology Group performance status score of 0 or 1 were eligible for inclusion.

年龄在18-75岁之间，之前未接受过治疗，经病理确认为不可切除的IIIB期、IIIC期或IV期鳞状非小细胞肺癌（NSCLC），以及东协作癌症组（Eastern Cooperative Oncology Group）表现状态评分为0或1的患者符合纳入标准。

Eligible patients were randomly assigned in a 1:1 ratio to receive ivonescimab or tislelizumab, in combination with paclitaxel and carboplatin for four cycles, followed by maintenance ivonescimab or tislelizumab monotherapy.

符合条件的患者以1:1的比例随机分配接受ivonescimab或tislelizumab治疗，与紫杉醇和卡铂联合使用四个周期，随后进行ivonescimab或tislelizumab单药维持治疗。

The primary endpoint was progression-free survivalassessed by the independent radiographic review committee as per Response Evaluation Criteria in Solid Tumours guidelines (version 1.1) in all randomly assigned patients.

主要终点是无进展生存期，由独立放射学审查委员会根据实体瘤反应评估标准（版本1.1）评估所有随机分配的患者。

Overall survivalwas a key secondary endpoint; an interim analysis was planned when approximately 225 overall survivalevents were observed, but it was triggered after 204 overall survivalevents to meet regulatory deadlines.

总生存是关键次要终点；原计划在观察到约225个总生存事件时进行中期分析，但为了满足监管截止日期，在观察到204个总生存事件后触发。

Safety, defined as adverse events and serious adverse events related to treatment, as well as adverse events related to immunity or VEGF blockade, were analysed in all randomly assigned patients who received at least one dose of the assigned study treatment.

安全性定义为与治疗相关的不良事件和严重不良事件，以及与免疫或VEGF阻断相关的不良事件，对所有至少接受一次指定研究治疗的随机分配患者进行了分析。

This study is registered at ClinicalTrials.gov (NCT05840016), has completed enrolment, and is ongoing for treatment and follow-up.

该研究已在ClinicalTrials.gov注册（NCT05840016），已完成招募，并正在进行治疗和随访。

Results

From Aug 17, 2023, to Jan 21, 2025, 761 patients were assessed for eligibility, and after 229 exclusions a total of 532 patients were randomly allocated (266 per group). 494 (93%) of patients were male and 38 (7%) of patients were female.

从2023年8月17日至2025年1月21日，共有761名患者被评估以确定其是否符合入选标准，经过229名患者的排除后，共有532名患者被随机分配（每组266名）。其中494名（93%）患者为男性，38名（7%）患者为女性。

The median age was 64 years (IQR 59-69).

中位年龄为64岁（四分位数间距59-69岁）。

At data cutoff (Feb 27, 2026), 204 deaths had occurred: 84 (32%) patients in the ivonescimab plus chemotherapy group and 120 (45%) in the tislelizumab plus chemotherapy group.

在数据截止日期（2026年2月27日），共发生204例死亡：ivonescimab联合化疗组中有84例（32%）患者，tislelizumab联合化疗组中有120例（45%）患者。

With a median follow-up of 21·4 months (95% CI 20·27-21·91), the median overall survivalwas 27·9 months (95% CI 27·89-not evaluable [NE]) with ivonescimab versus 23·7 months (20·11-NE) with tislelizumab (hazard ratiofor death 0·66 [95% CI 0·50-0·87]; pone-sided=0·0017), meeting the prespecified boundary (p<0·0049).

中位随访时间为21.4个月（95%置信区间20.27-21.91），ivonescimab治疗组的中位总生存期为27.9个月（95%置信区间27.89-未评估[NE]），而tislelizumab治疗组为23.7个月（20.11-NE）（死亡风险比为0.66 [95%置信区间0.50-0.87]；单侧p值=0.0017），达到了预设的界限（p<0.0049）。

The overall survivalbenefit with ivonescimab plus chemotherapy was consistent across key subgroups.

ivonescimab联合化疗的总生存益处在关键亚组中是一致的。

Treatment-related adverse events of grade 3 or higher occurred in 184 (69%) of 266 patients in the ivonescimab group and 156 (59%) of 265 patients in the tislelizumab group.

ivonescimab组266名患者中有184名（69%）和tislelizumab组265名患者中有156名（59%）发生了3级或更高级别的治疗相关不良事件。

The incidenceof grade 3 or higher haemorrhage was seven (3%) of 266 and two (1%) of 265, respectively.

3级或更高级别的出血发生率分别为266名患者中的七例（3%）和265名患者中的两例（1%）。

interpretation

Ivonescimab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survivalcompared with tislelizumab plus chemotherapy in previously untreated patients with advanced squamous NSCLC.

在之前未接受治疗的晚期鳞状非小细胞肺癌患者中，Ivonescimab联合化疗与tislelizumab联合化疗相比，在总生存期上显示出统计学上显著且具有临床意义的改善。

This regimen could provide a novel treatment option as first-line treatment in this patient group.

这种治疗方案可能为这一患者群体提供一种新的作为一线治疗的选择。

funding

Akeso Biopharma.

阿科索生物制药公司