PANKU-Breast01: Randomized phase III study of izalontamab brengitecan (iza-bren) in previously treated unresectable locally advanced or metastatic (LA/M) hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC)

doi:10.1016/s0140-6736(26)02096-9

PANKU-Breast01

Patient / Population Intervention / Exposure Comparison Outcome

In previously treated unresectable locally advanced or metastatic HR+/HER2- breast cancer, izalontamab brengitecan improved progression-free survival by blinded independent central review compared with chemotherapy of physician's choice.

N

383patients

Design

Randomised 1:1 phase III trial in patients with unresectable locally advanced or metastatic HR+/HER2- breast cancer who had progressed after at least one line of endocrine therapy and one or two lines of chemotherapy and had received CDK4/6 inhibitors and taxanes, comparing izalontamab brengitecan with treatment of physician's choice (eribulin, capecitabine, gemcitabine or vinorelbine); blinding of treatment not stated (NCT06343948).

Endpoint

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

ResultMedian PFS by BICR 8.18 mo (95% CI 6.93-8.58) with iza-bren vs 4.01 mo (95% CI 2.92-4.30) with TPC (HR 0.41; 95% CI 0.33-0.53; P<0.0001). Median follow-up for PFS 15.24 vs 13.63 mo. OS was immature at the interim analysis, with no detrimental effect observed. cORR by BICR 40.5% vs 20.2%; median DOR 6.93 vs 4.21 mo. Grade ≥3 TRAEs were predominantly haematological. 1.6% discontinued iza-bren due to TRAEs. Adjudicated ILD in 2 (1.1%) patients with iza-bren, all grade 1 or 2.

Lan B, Shi Y, Shao X, et al. The Lancet. 2026. 10.1016/s0140-6736(26)02096-9

Discussion & critique

The trial shows a large and statistically significant PFS gain by blinded central review for iza-bren over single-agent chemotherapy in heavily pretreated HR+/HER2- disease, with roughly doubled response rates. PFS is a surrogate, and OS was immature at this interim analysis, so a survival benefit has not been shown. The abstract does not say whether treatment was open label, and it gives no rates for grade ≥3 TRAEs or for the haematological toxicities it describes as predominant. The authors frame the result as relevant to patients in China, so how well it applies to other populations is unclear from the source.