In the phase III PANKU-Lung01 trial, the bispecific antibody–drug conjugate izalontamab brengitecan significantly improved progression-free survival compared with platinum-based chemotherapy in patients with EGFR-mutated advanced nonsquamous non–small cell lung cancer (NSCLC) whose disease had progressed on third-generation EGFR tyrosine kinase inhibitors. The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2026 (Abstract LBA71) and simultaneously published by Hong et al in The Lancet.
Study Details
PANKU-Lung01 was a multicenter, randomized, open-label phase III trial conducted at 73 sites in China. Eligible patients had locally advanced or metastatic nonsquamous NSCLC harboring sensitizing EGFR mutations, disease progression following treatment with a third-generation EGFR tyrosine kinase inhibitor, and no prior chemotherapy for advanced disease. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 or 1.
Between May 2024 and September 2025, 432 patients were randomly assigned to receive izalontamab brengitecan (n = 217) or chemotherapy (n = 215). Of these, 422 received treatment and were included in the primary efficacy analysis. Izalontamab brengitecan, which targets EGFR and HER3, was administered intravenously at 2.5 mg/kg on days 1 and 8 of each 3-week cycle. Chemotherapy consisted of pemetrexed plus carboplatin or cisplatin for four to six cycles, with pemetrexed maintenance permitted. The primary endpoint was progression-free survival assessed by blinded independent central review. Overall survival, objective response rate, duration of response, and safety were among the secondary endpoints.
Key Results
At the July 2026 data cutoff, median follow-up for progression-free survival was 14.6 months with izalontamab brengitecan and 15.2 months with chemotherapy. Median progression-free survival was 11.1 months (95% confidence interval [CI] = 9.2–12.7 months) vs 5.7 months (95% CI = 5.5–5.9 months), respectively (hazard ratio [HR] = 0.40, 95% CI = 0.31–0.51; one-sided P < .0001). The 12-month progression-free survival rates were 46.5% and 14.4%, respectively.
The confirmed objective response rate was 60.2% with izalontamab brengitecan compared with 34.5% with chemotherapy, with a median duration of response of 10.5 months vs 5.7 months, respectively. Progression-free survival results favored izalontamab brengitecan across prespecified subgroups, although the confidence interval crossed unity in the small subgroup with baseline central nervous system metastases.
At the interim overall survival analysis, median overall survival had not been reached with izalontamab brengitecan, compared with 19.4 months with chemotherapy (HR = 0.66, 95% CI = 0.47–0.91; one-sided P = .0058). However, the prespecified efficacy boundary for statistical significance was not crossed.
Treatment-related adverse events of grade 3 or higher occurred in 79% of patients receiving izalontamab brengitecan and 62% of those receiving chemotherapy, predominantly hematologic events. Dose reductions were required in 60% and 23% of patients, respectively. Treatment-related adverse events led to permanent discontinuation of at least one treatment component in 2% of patients in each group. One treatment-related death occurred in each group.
The investigators concluded: “In participants with EGFR-mutated advanced nonsquamous NSCLC after progression on third-generation EGFR [tyrosine kinase inhibitors], [izalontamab brengitecan] 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 III evidence for a bispecific antibody-drug conjugate and support [izalontamab brengitecan] as a potential treatment option in this population.”
Yunpeng Yang, MD, of the Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China, is the corresponding author for The Lancet article.
DISCLOSURE: The study was supported by Baili-Bio (Chengdu) Pharmaceutical. For full disclosures of the study authors, visit thelancet.com.
