Dr Wu on the Rationale for Investigating Iza-Bren in Advanced/Metastatic TNBC

“For the pretreated [patients, who have been] mostly treated with chemotherapy or immune checkpoint inhibitors before, there are not too many choices for clinicians. [Iza-bren will be] an important agent in the future to battle these difficult cases in our clinics.”

Jiong Wu, MD, PhD, a distinguished professor at Fudan University and vice president of the Fudan University Shanghai Cancer Center, discussed the mechanism of action of izalontamab brengitecan (iza-bren; BL-B01D1) and the significance of investigating this agent in the phase 3 PANKU-Breast02 trial (NCT06382142) for patients with unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC).

Wu began by discussing the clinical significance of evaluating biomarker expression in TNBC, focusing on the prevalence of EGFR and HER3 expression within tumor cells. He noted that high levels of EGFR are present in approximately 70% of TNBC cases, whereas HER3 is expressed in nearly all TNBC tumors. He explained that a dual blockade strategy that simultaneously targets both these signals could be essential for overcoming the mechanisms of drug resistance that often hinder current treatment regimens for patients with TNBC.

Furthermore, Wu focused on the limited therapeutic paradigm for this breast cancer subtype, identifying a lack of diverse targets in TNBC as a primary obstacle in the breast oncology field. He detailed the difficulties of treating patients who have been heavily pretreated with conventional chemotherapy or immune checkpoint inhibitors, noting that these patients often have few remaining therapeutic choices once those options are exhausted. He concluded that the introduction of dual-targeting agents represents a critical advancement for the future of the field, offering a necessary tool for addressing the most difficult and resistant cases encountered in clinical practice.

In data presented at the 2026 ASCO Annual Meeting, PANKU-Breast02 showed that patients who received iza-bren (n = 207) achieved a median progression-free survival by blinded independent central review of 8.5 months (95% CI, 6.9-9.8) vs 3.1 months (95% CI, 2.7-4.1) in patients treated with chemotherapy (n = 205; HR, 0.29; 95% CI, 0.22-0.38; P < .0001).