Iza-Bren Improves Survival in Metastatic Triple-Negative Breast Cancer

The investigational drug iza-bren (izalontamab brengitecan) improved both progression-free survival (PFS) and overall survival (OS) compared with standard chemotherapy in patients with previously treated, unresectable locally advanced or metastatic triple-negative breast cancer (TNBC), according to findings from the phase 3 PANKU-Breast02 trial presented at the 2026 ASCO Annual Meeting.

PFS refers to the length of time a patient lives without their cancer growing or worsening. OS refers to the length of time a patient lives after starting treatment, regardless of whether their cancer progresses.

"The results from this phase 3 study support iza-bren as a new standard of care for patients with pretreated metastatic triple-negative breast cancer," Dr. Jiong Wu, of Fudan University Cancer Institute, said during the presentation.

Researchers reported that iza-bren reduced the risk of cancer progression or death by 71% compared with chemotherapy.

The study enrolled 418 patients at 81 centers across China. All patients had experienced disease progression after one or two previous lines of treatment, including a taxane-based therapy. Patients were randomly assigned to receive either iza-bren or a physician's choice of chemotherapy, which could include eribulin, capecitabine, gemcitabine or vinorelbine.

At a planned interim analysis, the study met both of its primary goals.

Patients treated with iza-bren experienced a median PFS of 8.5 months compared with 3.1 months for those treated with chemotherapy. The hazard ratio was 0.29, meaning patients who received iza-bren had a 71% lower risk of disease progression or death than those who received chemotherapy.

At six months, 62% of patients treated with iza-bren remained free from disease progression compared with 17.6% of patients in the chemotherapy group.

The survival benefit also extended to OS. Patients who received iza-bren lived a median of 15.9 months compared with 12.5 months for patients treated with chemotherapy. The hazard ratio was 0.6, meaning iza-bren reduced the risk of death by 40% compared with chemotherapy.

Iza-bren is a bispecific antibody-drug conjugate (ADC), a type of targeted therapy designed to attach to cancer cells and deliver chemotherapy directly to them. The drug targets two proteins, EGFR and HER3, which may help improve its ability to identify and attack cancer cells.

The treatment also led to higher response rates.

The objective response rate (ORR), which measures the percentage of patients whose tumors shrink by a predefined amount or disappear after treatment, was 51.7% with iza-bren compared with 20.5% with chemotherapy. Complete responses, meaning no detectable evidence of cancer on imaging, occurred in 3.9% of patients treated with iza-bren.

The disease control rate, which includes patients whose cancer shrinks or remains stable, was 83.1% with iza-bren versus 59% with chemotherapy.

Among patients whose cancer responded to treatment, the median duration of response (DOR), or how long the response lasted, was 8.3 months with iza-bren compared with 4 months with chemotherapy.

Researchers reported that the benefit of iza-bren was seen across multiple patient groups. This included patients whose tumors had different levels of HER2 expression, patients with liver metastases and patients who had previously received anti-PD-(L)1 immunotherapy.

In patients whose tumors were classified as HER2 IHC 0, median PFS was 8.3 months with iza-bren and 2.6 months with chemotherapy. The hazard ratio was 0.28, meaning the risk of disease progression or death was reduced by 72% with iza-bren.

Among patients with HER2-low disease, median PFS was 9.7 months with iza-bren compared with 4.1 months with chemotherapy. The hazard ratio was 0.32, meaning the risk of progression or death was reduced by 68%.

Regarding safety, side effects occurred in nearly all patients in both treatment groups. Serious side effects and severe side effects were reported more frequently with iza-bren than with chemotherapy.

The most common severe side effects with iza-bren were decreases in neutrophils (58%), white blood cells (56%), platelets (52.7%) and red blood cells causing anemia (46.9%).

Febrile neutropenia, a potentially serious condition involving low white blood cell counts and fever, occurred in 5.3% of patients receiving iza-bren compared with 0.5% of patients receiving chemotherapy.

Dose reductions and treatment interruptions were common, with 63.3% of patients requiring each type of adjustment. However, treatment discontinuation due to side effects was uncommon, occurring in 1.9% of patients treated with iza-bren and 0.5% of those receiving chemotherapy.

Researchers also monitored for interstitial lung disease (ILD), an inflammation of lung tissue that has been associated with some ADCs. One patient (0.5%) treated with iza-bren developed grade 2 ILD, and no grade 3 or higher cases were reported.

Overall, the findings suggest that iza-bren may offer a meaningful survival advantage for patients with previously treated metastatic TNBC, with side effects that investigators described as manageable with monitoring and supportive care.

Reference

1. “Izalontamab brengitecan (iza-bren) versus physician’s choice of chemotherapy in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC): A randomized phase III study” by Dr. Jiong Wu, et al., Journal of Clinical Oncology.

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