Izalontamab brengitecan versus platinum-based chemotherapy in EGFR-mutated advanced non-squamous non-small-cell lung cancer after progression on third-generation EGFR tyrosine kinase inhibitors (PANKU-Lung01): a multicentre, randomised, open-label, phase 3 trial in China

Key numbers

• 95% CI 12.9-16.7
• 95% CI 0.31-0.51

Background Izalontamab brengitecan (iza-bren) is a first-in-class bispecific antibody-drug conjugate targeting epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3) and has shown antitumour activity in EGFR-mutated non-small-cell lung cancer (NSCLC). We compared iza-bren with platinum-based chemotherapy in participants with EGFR-mutated advanced non-squamous NSCLC after progression on third-generation EGFR tyrosine kinase inhibitors (TKIs). Methods In this multicentre, randomised, open-label, phase 3 trial (PANKU-Lung01) conducted at 73 sites in China, eligible participants had EGFR-mutated locally advanced or metastatic non-squamous NSCLC, disease progression after third-generation EGFR TKIs, and had received no previous chemotherapy for advanced disease. Participants were randomly assigned (1:1) to receive iza-bren (2·5 mg/kg intravenously on days 1 and 8 of each 3-week cycle) or pemetrexed plus carboplatin or cisplatin for four to six cycles, with pemetrexed maintenance permitted in participants without progression. The primary endpoint was progression-free survival assessed by blinded independent central review (BICR). The primary analysis included all randomly assigned participants who received at least one dose of study treatment (modified intention-to-treat population). We report the prespecified final progression-free survival and interim overall survival analyses. This trial is registered with ClinicalTrials.gov, NCT06382116. Findings Between May 22, 2024, and Sept 1, 2025, we screened 654 participants. After 222 (34%) were excluded, 432 (66%) participants were randomly assigned to iza-bren (n=217 [50%]) or chemotherapy (n=215 [50%]); 422 (98%) received study treatment (216 [51%] in the iza-bren group and 206 [49%] in the chemotherapy group) and comprised the modified intention-to-treat population. At the data cutoff (July 15, 2026; median follow-up for progression-free survival 14·6 months [95% CI 12·9-16·7] in the iza-bren group vs 15·2 months [11·2-18·2] in the chemotherapy group), median BICR-assessed progression-free survival was 11·1 months (9·2-12·7) with iza-bren versus 5·7 months (5·5-5·9) with chemotherapy (hazard ratio [HR] 0·40 [95% CI 0·31-0·51]; one-sided p<0·0001). Treatment-related adverse events of grade 3 or worse occurred in 170 (79%) of 216 participants in the iza-bren group and 128 (62%) of 206 in the chemotherapy group (predominantly haematological); treatment-related adverse events led to permanent discontinuation of at least one study-treatment component in four (2%) participants in each group and treatment-related deaths occurred in one participant in each group. Treatment-related interstitial lung disease occurred in two (1%) participants in the iza-bren group and none in the chemotherapy group. Interpretation In participants with EGFR-mutated advanced non-squamous NSCLC after progression on third-generation EGFR TKIs, iza-bren significantly prolonged progression-free survival, although treatment-related adverse events of grade 3 or worse were more frequent than with chemotherapy. To our knowledge, these findings provide the first phase 3 evidence for a bispecific antibody-drug conjugate and support iza-bren as a potential treatment option in this population. Funding Baili-Bio (Chengdu) Pharmaceutical.

Shaodong Hong, Ting Zhou, Xue Hou, Xiangjiao Meng, Zhihuang Hu, Wei Zheng, Jiuwei Cui, Yongzhong Luo, Lin Wu, Meijuan Huang, Haipeng Xu, Jie Hu, Yanqiu Zhao, Wenxiu Yao, Yonggui Hong, Jun Cai, Yu Zhang, Chunxia Su, Conghua Xie, Ruoyu Wang, Xiang Li, Qiong He, Liang Zhang, Ruiling Ning, Daren Lin, Tongmei Zhang, Tienan Yi, Liqiang Zhong, Siyuan Huang, Hui Zhao, et al.

Leverage3 / 5

A method or resource many groups across the field will adopt within a year.

10% of this desk’s rubric

Magnitude4 / 5

A qualitative jump: a capability or regime that did not exist before.

20% of this desk’s rubric

Evidence5 / 5

Definitive: phase 3 randomized evidence on hard endpoints, multi-lab replication, or community verification at scale.

32% of this desk’s rubric

Novelty3 / 5

A genuinely new approach to an open problem.

8% of this desk’s rubric

Trajectory2 / 5

Some room to improve with obvious engineering.

5% of this desk’s rubric

Stakes3 / 5

Meaningful benefit to many people within a few years.

25% of this desk’s rubric

• Citations0 (reference 20, via openalex, Oct 28, 2026, 06:17 UTC)

• Reviewed by heuristic-v10 on Oct 28, 2026, 06:17 UTC. Paper type: clinical.
• Categories: Journal Article
• LEAD, No.1 in the Front page edition of October 28, 2026.
• LEAD, No.1 in the Medicine edition of October 28, 2026.