Izalontamab brengitecan (iza-bren) significantly improved progression-free survival (PFS) vs platinum-based chemotherapy in patients with EGFR-mutated nonsquamous non–small cell lung cancer (NSCLC) whose disease progressed on a third-generation EGFR TKI, according to interim findings from the phase 3 PANKU-Lung01 trial (NCT06382116) presented at the
At a median follow-up of 14.6 months, the median PFS by blinded independent central review (BICR) was 11.1 months (95% CI, 9.2-12.7) with iza-bren (n = 216) vs 5.7 months (95% CI, 5.5-5.9) with chemotherapy (n = 206; HR, 0.40; 95% CI, 0.31-0.51; 1-sided P < .0001).¹ The 6-month PFS rates were 75.1% and 42.9%, respectively, and the 12-month rates were 46.5% and 14.4%.
Overall survival (OS) data were immature at the interim analysis. The median OS was not reached (95% CI, 19.3-not reached) with iza-bren vs 19.4 months (95% CI, 16.4-22.5) with chemotherapy, and the 12-month OS rates were 83.0% (95% CI, 77.3%-87.5%) and 72.9% (95% CI, 66.1%-78.5%), respectively. Moreover, the confirmed objective response rate (ORR) by BICR was 60.2% (95% CI, 53.3%-66.8%) with iza-bren vs 34.5% (95% CI, 28.0%-41.4%) with chemotherapy, a difference of 25.6% (95% CI, 16.2%-34.6%; odds ratio, 2.9; 95% CI, 1.9-4.3).
A New Targeted Approach After EGFR TKI Resistance
- In phase 3 PANKU-Lung01, izalontamab brengitecan (iza-bren) improved median PFS to 11.1 months vs 5.7 months with platinum-based chemotherapy after progression on a third-generation EGFR TKI (HR, 0.40; P < .0001). OS data remain immature.
- The confirmed objective response rate was 60.2% with iza-bren vs 34.5% with chemotherapy, and the median duration of response was 10.4 vs 5.7 months.
- Grade 3 or higher treatment-related adverse effects occurred in 78.7% of patients receiving iza-bren vs 62.1% with chemotherapy.
Presenting author Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, said that “these results support iza-bren as a promising new treatment option for [patients with] EGFR-mutant NSCLC with EGFR TKI resistance.”
How was the phase 3 PANKU-Lung01 trial evaluating iza-bren in EGFR-mutated NSCLC designed?
Iza-bren is a bispecific antibody-drug conjugate (ADC) that targets EGFR and HER3 and carries a topoisomerase I inhibitor payload via a cleavable linker. In a global phase 1 dose-expansion study (NCT05983432), the agent produced responses in patients with EGFR-mutated NSCLC after osimertinib, and those data established the recommended phase 3 dose for the global IZABRIGHT-Lung01 trial (NCT07100080).³
The open-label, multicenter PANKU-Lung01 trial enrolled patients with locally advanced or metastatic nonsquamous NSCLC harboring an EGFR exon 19 deletion or L858R mutation whose disease progressed on a third-generation EGFR TKI, after up to 2 prior lines of EGFR TKI therapy.¹ Patients had measurable disease, and an ECOG performance status of 0 or 1. Those with treated or stable central nervous system (CNS) metastases were permitted.
Patients were randomly assigned 1:1 to iza-bren at 2.5 mg/kg on days 1 and 8 every 3 weeks or to pemetrexed at 500 mg/m² plus cisplatin at 75 mg/m² or carboplatin at an area under the curve of 5 every 3 weeks. Randomization was stratified by ECOG performance status (0 vs 1), CNS metastases (yes vs no), and prior antiangiogenic therapy (yes vs no). Treatment continued until progressive disease by RECIST 1.1 or unacceptable toxicity.