PANKU-Lung01: Randomized phase III study of izalontamab brengitecan (iza-bren) in EGFR-mutant non-squamous non-small cell lung cancer (NSCLC) after progression on a third-generation EGFR TKI

PANKU-Lung01

Patient / Population Intervention / Exposition Vergleich Endpunkt

In patients with EGFR-mutant non-squamous NSCLC after progression on a third-generation EGFR TKI, iza-bren improved progression-free survival compared with platinum-based chemotherapy.

N

422Patienten

Design

Randomised 1:1 phase III trial in patients with locally advanced or metastatic non-squamous NSCLC with an EGFR sensitising mutation (exon 19 deletion or L858R) and progression on a prior third-generation EGFR TKI, comparing iza-bren with platinum-based chemotherapy (pemetrexed plus cisplatin or carboplatin) (NCT06382116).

Endpunkt

Progression-free survival assessed by blind independent central review (BICR).

ErgebnisMedian PFS by BICR 11.14 mo (95% CI 9.17-12.68) with iza-bren vs 5.65 mo (95% CI 5.45-5.95) with platinum-based chemotherapy (HR 0.40; 95% CI 0.31-0.51; P <0.0001). Median follow-up for PFS was 14.6 vs 15.2 mo. OS was immature (HR 0.66; 95% CI 0.47-0.91). Confirmed ORR by BICR 60.2% vs 34.5%. Median DOR 10.45 vs 5.68 mo. Grade 3 or higher TRAEs were predominantly haematological. 1.9% of patients on iza-bren discontinued treatment due to TRAEs. Adjudicated ILD occurred in two patients (0.9%) on iza-bren, one grade 3 and one grade 1.

Zhang L, Yang Y, Meng X, et al. Presented at ESMO Congress 2026, abstract LBA71, 26 October. Not yet published.

Diskussion & Kritik

This phase III trial shows a large and statistically significant PFS gain for iza-bren over platinum-based chemotherapy, assessed by blinded central review, with a higher response rate and longer duration of response. The PFS result comes from a pre-planned interim analysis and OS is immature, with only a hazard ratio and no P value reported, so a survival benefit is not yet established. The abstract does not state whether patients or investigators were blinded to treatment, gives no overall grade 3 or higher adverse event rates, and says nothing about subsequent therapy or crossover after chemotherapy. The authors limit their conclusion to China, and a separate global study is ongoing, so whether the result applies more widely is still open.