TL;DR
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A phase III trial in China found that izalontamab brengitecan (iza-bren) extended median progression-free survival to 11.1 months, compared with 5.7 months for chemotherapy, among patients with advanced EGFR-mutated lung cancer after third-generation EGFR inhibitors. Severe treatment-related adverse events were more common with iza-bren, and overall survival results remain immature.
A phase III trial found that izalontamab brengitecan (iza-bren) extended median progression-free survival to 11.1 months, compared with 5.7 months with chemotherapy, in people with advanced EGFR-mutated non-small cell lung cancer whose disease progressed after third-generation EGFR inhibitors. The China-based PANKU-Lung01 results were reported at the ESMO annual congress and published in The Lancet; overall survival data are not yet mature.
The trial randomly assigned 432 patients to iza-bren or pemetrexed combined with carboplatin or cisplatin. Patients had locally advanced or metastatic non-squamous lung cancer that had progressed after a third-generation EGFR tyrosine kinase inhibitor (TKI), and had not previously received chemotherapy for advanced disease. The study ran at 73 sites in China, with enrollment from May 2024 to September 2025. Researchers measured the primary outcome, progression-free survival (PFS), through blinded independent central review.
The estimated risk of progression or death was lower with iza-bren: the hazard ratio was 0.40 (95% confidence interval 0.31-0.51). Confirmed tumor responses occurred in 60.2% of patients receiving iza-bren and 34.5% of those receiving chemotherapy. Median duration of response was 10.5 months versus 5.7 months. The trial report said the PFS benefit extended across all prespecified subgroups, though the supplied results do not provide detailed subgroup estimates.
Interim overall survival estimates favored iza-bren, but the data were immature: median survival had not been reached in that group, compared with 19.4 months in the chemotherapy group. The reported stratified hazard ratio was 0.66 (95% CI 0.47-0.91). These interim figures do not establish the final survival effect.
Side effects were also more frequent in the iza-bren group. Grade 3 or higher treatment-related adverse events occurred in 79% of patients receiving iza-bren and 62% receiving chemotherapy; serious treatment-related events occurred in 43% and 19%, respectively. Severe blood-related effects included decreased neutrophils, white blood cells and platelets, as well as anemia. Febrile neutropenia was reported in 6% of the iza-bren group and none of the chemotherapy group. Treatment-related adverse events led to discontinuation in 2% of patients in each group.
A Later-Line Option Under Study
The findings address a treatment gap after resistance to third-generation EGFR TKIs. These drugs are standard treatment for advanced EGFR-mutated lung cancer, but the source report says most patients eventually develop resistance. Platinum-based chemotherapy is a common subsequent option. In this trial, iza-bren produced longer PFS and more tumor responses than that chemotherapy regimen, offering evidence that a targeted antibody-drug conjugate could be useful in this setting.
The results also need to be weighed against the higher rates of severe and serious treatment-related side effects. The trial compares iza-bren with chemotherapy in a defined group of patients in China; it does not by itself establish how the drug should be used across broader populations, or whether it improves overall survival. Treatment decisions require consideration of both potential benefit and toxicity by qualified oncology professionals.
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After EGFR Inhibitor Resistance
EGFR-mutated non-small cell lung cancer can initially respond to EGFR TKIs, but resistance can develop. After progression on a third-generation TKI, the trial participants had not received chemotherapy for advanced disease and were assigned either iza-bren or a platinum-based pemetrexed regimen, with pemetrexed maintenance allowed for patients whose disease did not progress.
Iza-bren is a bispecific antibody-drug conjugate that targets EGFR and HER3. The source report says the U.S. Food and Drug Administration granted it breakthrough therapy designation for previously treated advanced EGFR-mutated lung cancer based on phase I and II results. That designation is not the same as approval. Separate global registration studies are underway in patients after third-generation TKI treatment and in the first-line setting.
The drug was also presented at the same ESMO meeting in a randomized trial involving heavily pretreated hormone receptor-positive breast cancer. That is a separate study and does not change what the lung cancer trial establishes.
“These results support iza-bren as a promising new treatment option for EGFR-mutant NSCLC patients with EGFR TKI resistance.”
— Li Zhang, MD, of Sun Yat-sen University Cancer Center, presenting the PANKU-Lung01 results
Survival and Patient Selection
Final overall survival results are not available, and the interim comparison cannot show whether the PFS gain will translate into longer overall survival. The reported trial was conducted at sites in China; the supplied material does not establish whether outcomes will be the same in other health systems or populations.
Further questions include which patients are most likely to benefit, how the drug performs in people with central nervous system metastases, what resistance develops, and how iza-bren should be sequenced with other treatments. Ekman raised these as areas for additional study. The source material does not provide detailed results for every subgroup or a full account of all adverse-event types.
Global Trials and Final Survival Data
Global studies named in the report include IZABRIGHT-Lung01, for EGFR-mutated lung cancer after progression on a third-generation EGFR TKI, and IZABRIGHT-Lung02, in the first-line setting. Their findings may help clarify how iza-bren performs beyond the China-based PANKU-Lung01 population and where it might fit in treatment sequencing.
Follow-up from PANKU-Lung01 will be needed for more mature overall survival results. Researchers and regulators will also need fuller evidence on safety, patient selection and the drug’s role relative to existing treatments. The source report does not give dates for those results or specify a regulatory decision based on the phase III trial.
Key Questions
What did the PANKU-Lung01 trial find?
The phase III trial reported median progression-free survival of 11.1 months with iza-bren and 5.7 months with pemetrexed plus platinum chemotherapy in patients with advanced EGFR-mutated lung cancer after third-generation EGFR TKIs.
Did iza-bren improve overall survival?
Overall survival data were immature. The interim estimate favored iza-bren, but median survival had not been reached in that group, so the final survival effect is not yet known.
What side effects were reported?
Grade 3 or higher treatment-related adverse events occurred in 79% of the iza-bren group and 62% of the chemotherapy group. Blood-related effects, including low neutrophil and platelet counts and anemia, were among the common severe events reported.
Is iza-bren approved for this lung cancer setting?
The source report says the FDA granted iza-bren breakthrough therapy designation based on earlier studies. That designation is not an approval; the supplied material does not report a marketing authorization for this indication.
What studies are planned or underway?
The report identifies global registration studies after third-generation EGFR TKI progression, IZABRIGHT-Lung01, and in the first-line setting, IZABRIGHT-Lung02. It does not provide expected reporting dates.
Source: medpagetoday.com
