ESMO Congress 2026

Antibody-drug conjugates (ADCs) are now an established class within breast cancer targeted therapy, joining endocrine therapy, HER2-directed drugs, CDK4/6 and PI3K/AKT/mTOR inhibitors, and immunotherapy in the current systemic treatment landscape, while resistance and toxicity remain core factors limiting outcomes ^[6]. Izalontamab brengitecan (iza-bren) is a bispecific EGFR×HER3 ADC conjugated to a topoisomerase I (TOP1) inhibitor, and it entered this landscape with Phase 3 data this time.

PANKU-Breast01 (LBA50), reported at ESMO 2026, is a randomised phase 3 trial conducted in China, enrolling patients with HR+/HER2− metastatic breast cancer previously treated with CDK4/6 inhibitors and 1–2 prior chemotherapy lines (~70% with only 1 line), comparing iza-bren against physician's choice chemotherapy (TPC). Median PFS was 8.18 vs 4.01 months, HR 0.41 (95% CI 0.33–0.53; p<0.0001), a 59% reduction in the hazard of progression or death; ORR was 40.5% vs 20.2%, and median DOR 6.93 vs 4.21 months; OS remains immature. Safety was dominated by hematologic toxicity, with ~50% of patients experiencing grade ≥3 anemia, neutropenia, and thrombocytopenia, and most patients requiring dose reductions; ILD occurred in only 1.1% (all grade 1–2); primary prophylactic G-CSF was not required by the protocol. The results were published online simultaneously in The Lancet Oncology.

Relative to existing knowledge, this readout advances the field: in a population encompassing all HER2 statuses, the bispecific EGFR/HER3 ADC delivered a significant PFS benefit over chemotherapy and doubled the ORR; the on-site expert LoiSher judged the efficacy broadly comparable to DB04, noting this trial covered all HER2 rather than HER2-low only. It must be noted, however, that this was a head-to-head comparison against chemotherapy, and on-site commentary also pointed out that in an era when T-DXd and SG are already in use, superiority over chemotherapy alone is not enough; the added value of bispecific targeting, particularly efficacy after prior TOP1-ADCs, remains uncertain, and these are the key data defining its place in the treatment sequence.

The limitations are equally clear: OS remains immature and the hematologic toxicity burden is substantial, echoing the concern raised in the literature that toxicity limits breast cancer treatment outcomes ^[6]; combined with the unresolved what-next question of sequencing after other ADCs, this phase 3 evidence from a Chinese population still awaits further data to define its therapeutic positioning.