Iza-Bren Significantly Improves PFS vs Chemotherapy in Pretreated HR+/HER2– Advanced Breast Cancer

Izalontamab brengitecan (BL-B01D1; iza-bren) produced a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs treatment of physician's choice chemotherapy in patients with previously treated unresectable locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer, according to findings from of the phase 3 PANKU-Breast01 trial (NCT06343948) presented at the 2026 European Society for Medical Oncology (ESMO) Congress.¹

The EGFR x HER3 bispecific antibody-drug conjugate (ADC) also improved responses among patients.

At a median follow-up of 15.2 months, the median PFS by blinded independent central review (BICR) was 8.2 months (95% CI, 6.9-8.6) with iza-bren (n = 190) vs 4.0 months (95% CI, 2.9-4.3) with chemotherapy (n = 193; HR, 0.41; 95% CI, 0.33-0.53; P < .0001).¹

The 6-, 9-, and 12-month PFS rates were 62.8%, 41.8%, and 26.5% in the iza-bren arm vs 24.2%, 14.4%, and 9.2% in the chemotherapy arm, respectively. The overall response rate (ORR) was 40.5% (95% CI, 33.5%-47.9%) with iza-bren vs 20.2% (95% CI, 14.8%-26.6%) with chemotherapy.

"Iza-bren demonstrated a statistically significant and clinically meaningful improvement in PFS vs chemotherapy," said Bo Lan, MD, of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing. “The results support iza-bren as a potential new standard of care option in this population.”

In a prior phase 1 study, the agent elicited a confirmed ORR of 36.4% and a median PFS of 6.9 months in patients with HER2-negative locally advanced or metastatic breast cancer. The agent is also being developed in EGFR-mutated non–small cell lung cancer, where data presented at the 2026 IASLC World Conference on Lung Cancer demonstrated an ORR of 30.9% (95% CI, 21.1%-42.1%) for the ADC.²

How was PANKU-Breast01 designed?

The open-label, multicenter, randomized study was conducted at 72 centers across China.¹ Eligible patients had unresectable locally advanced or metastatic horomone receptor-positive, HER2-negative breast cancer that progressed after at least 1 line of endocrine therapy. Patients also needed to have received 1 or 2 prior lines of chemotherapy, have prior exposure to CDK4/6 inhibitors and taxanes, measurable disease per RECIST 1.1 criteria, and an ECOG performance status of 0 or 1.

Patients were randomly assigned to iza-bren at 2.5 mg/kg on days 1 and 8 every 3 weeks or chemotherapy, which consisted of eribulin at 1.4 mg/m² on days 1 and 8, capecitabine at 1000-1250 mg/m² twice daily on days 1-14, gemcitabine at 1000 mg/m² on days 1 and 8, or vinorelbine at 25 mg/m² on days 1 and 8, each given every 3 weeks. Randomization was stratified by number of prior chemotherapy lines, central nervous system metastases, and HER2 expression. PFS by BICR served as the primary end point, and overall survival (OS) was the key secondary end point.

Baseline characterstics revealed that patients had a median age of 54.0 years in both arms, 71.1% and 72.0% of patients in the iza-bren and chemotherapy arms, respectively, had received 1 prior line of chemotherapy, and 71.6% and 71.0% had baseline liver metastases. HER2 expression was immunohistochemistry (IHC) 0 in 33.7% and 34.2% of patients and IHC 1+ in 38.4% and 38.3%.

What did the secondary and subgroup analyses show?

The difference in confirmed ORR between the arms was 20.2% (95% CI, 11.2%-29%; odds ratio, 2.7; 95% CI, 1.7-4.3). Disease control rates were 86.3% (95% CI, 80.6-90.9) with iza-bren compared with 63.7% (95% CI, 56.5%-70.5%) with chemotherapy, and the median duration of response was 6.9 months vs 4.2 months, respectively. Progressive disease was the best response in 8.4% vs 31.6% of patients in iza-bren and chemotherapy arms.

The PFS benefit was consistent across subgroups, including patients with 2 prior chemotherapy lines (HR, 0.31; 95% CI, 0.20-0.50), HER2 IHC 1+ disease (HR, 0.53; 95% CI, 0.36-0.78), and in those with liver metastases at baseline (HR, 0.40; 95% CI, 0.30-0.53).

OS data were immature at a median follow-up of 17.8 months, with no detrimental effect observed.

What did the safety analysis show?

Treatment-related adverse effects (TRAEs) occurred in 99.5% of patients in the iza-bren arm vs 97.4% of patients in the chemotherapy arm, including grade 3 or higher TRAEs in 85.3% vs 65.8% and treatment-related serious AEs in 41.6% vs 11.4%. TRAEs led to dose reduction in 64.7% vs 28.5% of patients, dose interruption in 56.3% vs 37.8%, and discontinuation in 1.6% vs 1.0%. Moreover, TRAEs led to death in 2 patients given iza-bren and 1 patient given chemotherapy. The median duration of treatment was 7.3 months (range, 0.3-22.5) with iza-bren vs 4.3 months (range, 0.3-26.0) with chemotherapy.

The most frequent TRAEs with iza-bren were hematologic, and grade 3 or higher events included neutropenia (53.7%), anemia (49.5%), leukopenia (48.4%), and thrombocytopenia (46.3%). According to investigators, these events were handled with growth factor support, dose delays and reductions, and primary prophylaxis with granulocyte colony-stimulating factor was not required. Grade 3 or higher anemia took a median of 6 days to resolve, and grade 3 or higher neutropenia and thrombocytopenia typically resolved within 2 and 3 days, respectively. Among patients in the iza-bren arm, 73% were given platelet-elevating agents, 15% underwent platelet transfusion, and 10% underwent blood transfusion.²

Among patients treated with iza-bren, 7.9% developed febrile neutropenia and 4.7% experienced grade 3 or higher infections. Most nonhematologic AEs were low grade in each arm, with alopecia (53.2%; 43.0%) and asthenia (49.5%; 22.3%) occurring most often. Two patients in the iza-bren arm had adjudicated treatment-related interstitial lung disease, with 1 case being grade 1 and the other being grade 2.

References

1. Lan B, Shi Y, Shao X, et al. Izalontamab brengitecan for HR+/HER2- breast cancer in China (PANKU-Breast01): a randomised, phase 3 trial. Lancet. Published online October 23, 2026. doi:10.1016/S0140-6736(26)02096-9
2. Spira A, Chae Y, Gregorc V, et al. Phase 1 global study of iza-bren in patients with metastatic EGFR-mutated NSCLC: results of the randomized dose expansion cohort. Presented at: International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer; September 12-15, 2026; Seoul, South Korea. Abstract OA10.01.