Izalontamab brengitecan (Iza-bren; BL-B01D1), a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, for patients with EGFR-mutated NSCLC: pooled analysis of phase I and phase II trials.

Izalontamab brengitecan (Iza-bren; BL-B01D1) is a first-in-class bispecific antibody-drug conjugate targeting EGFR and human epidermal growth factor receptor 3 (HER3) with preclinical and early clinical activity.

Izalontamab brengitecan（Iza-bren; BL-B01D1）是一种针对EGFR和人类表皮生长因子受体3（HER3）的新型双特异性抗体药物偶联物，具有临床前和早期临床活性。

patients_and_methods

We pooled individual patient data from a phase Ia/Ib dose-escalation/expansion trial (BL-B01D1-101; NCT05194982) and a phase II multicohort trial (BL-B01D1-203; NCT05880706) in patients with advanced EGFR-mutated NSCLC who had disease progression on prior EGFR TKI therapy.

我们汇总了来自一项Ia/Ib期剂量递增/扩展试验(BL-B01D1-101; NCT05194982)和一项II期多队列试验(BL-B01D1-203; NCT05880706)的个体患者数据，这些试验针对的是先前接受EGFR酪氨酸激酶抑制剂治疗后疾病进展的晚期EGFR突变型非小细胞肺癌患者。

Key endpoints were confirmed objective response rate(cORR), disease control rate (DCR), duration of response (DoR), progression-free survival(PFS), overall survival(OS), and safety.

关键终点包括确认的客观缓解率(cORR)、疾病控制率(DCR)、缓解持续时间(DoR)、无进展生存期(PFS)、总生存期(OS)和安全性。

The recommended phase II dose (RP2D) was 2.5 mg/kg on days 1 and 8 every 3 weeks.

推荐的II期剂量（RP2D）为每3周的第1天和第8天，剂量为2.5 mg/kg。

Results

A total of 171 patients were included (data cut-off 30 June 2025; median follow-up 20.5 months).

共有171名患者被纳入研究（数据截止日期为2025年6月30日；中位随访期为20.5个月）。

In the pooled population, cORR was 47.4% [95% confidence interval(CI) 39.7% to 55.1%] and DCR was 81.3% (95% CI 74.6% to 86.8%); median DoR was 8.5 months (95% CI 6.9-11.2 months), median PFS was 6.9 months (95% CI 5.5-9.6 months), and median OS was 24.8 months (95% CI 18.5 months to not reached).

在汇总的人群中，cORR为47.4%（95%置信区间39.7%至55.1%），DCR为81.3%（95%置信区间74.6%至86.8%）；DoR的中位数为8.5个月（95%置信区间6.9-11.2个月），PFS的中位数为6.9个月（95%置信区间5.5-9.6个月），OS的中位数为24.8个月（95%置信区间18.5个月至未达到）。

Efficacy at the RP2D (n = 121) was consistent (cORR 48.8%; DCR 81.0%; median PFS 6.9 months; median OS 24.8 months).

在RP2D（n = 121）的疗效是稳定的（cORR 48.8%；DCR 81.0%；PFS的中位数为6.9个月；OS的中位数为24.8个月）。

In chemotherapy-naive, post-TKI patients treated at the RP2D (n = 50), cORR was 56.0%, DCR was 90.0%, median DoR was 13.7 months, median PFS was 12.5 months, and median OS was not reached.

在接受RP2D治疗的化疗未经治疗的TKI后患者中（n = 50），cORR为56.0%，DCR为90.0%，DoR中位数为13.7个月，PFS中位数为12.5个月，OS中位数未达到。

Treatment-related adverse events occurred in 98.8% (grade ≥3: 70.2%), predominantly hematologic; interstitial lung disease was rare (0.6%, all grade 1).

治疗相关的不良事件发生在98.8%的患者中（3级或以上：70.2%），主要是血液学的；间质性肺病很少见（0.6%，均为1级）。

Discontinuation for treatment-related adverse events was 1.2%; no treatment-related deaths were reported.

因治疗相关不良事件而停药的比例为1.2%；未报告与治疗相关的死亡事件。

Conclusions

In this exploratory post hoc pooled analysis, Iza-bren demonstrated promising antitumor activity and a manageable safety profile in heavily pretreated EGFR-mutated NSCLC.

在这项探索性的事后汇总分析中，Iza-bren在经过重度预处理的EGFR突变型非小细胞肺癌患者中显示出有希望的抗肿瘤活性和可控的安全性特征。

These findings are hypothesis-generating and are being further evaluated in ongoing randomized trials.

这些发现具有启发性，并且正在正在进行的随机试验中进一步评估。