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 Comparaison Critère de jugement

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

422patients

Schéma

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).

Critère

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

RésultatMedian 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.

Discussion et critique

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.