During the upcoming European Society for Medical Oncology (ESMO) Breast Cancer 2025 Annual Congress taking place May 14 – May 17 in Munich, Germany, SystImmune will present data from a Phase 1 clinical study evaluation Izalontamab Brengitecan (iza-bren; previously know as Bl-B01D1; see ADC Drugmap).
Izalontamab brengitecan is a potentially firs-in-class EGFRxHER3 bispecific topoisomerase inhibitor-based antibody-drug conjugate being jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement.
Izalontamab brengitecan is a bispecific antibody-drug conjugate (ADC) that targets both EGFR and HER3, proteins are highly expressed in most epithelial tumors. The targeting EGFR x HER3 bispecific antibody is conjugated to a novel topoisomerase inhibitor payload (Ed-04), a derivative of the alkaloid camptothecin, via a stable tetrapeptide-based cleavable linker. The tetravalent izalontamab brengitecan has two binding domains for distinct Growth Factor Receptors that drive cancer cell proliferation and survival.
Izalontamab brengitecan blocks EGFR and HER3 signals to cancer cells, reducing proliferation and survival signals. Upon antibody mediated internalization, the investigational drug is trafficked to cancer cell lysosomes and liberates its therapeutic payload that induces genotoxic stress activating pathways leading to cancer cell death.
ESMO Breast 2025
The data to be presented at ESMO Breast 2025 includes updated results from an ongoing phase 1 clinical trial of izalontamab brengitecan in patients with locally advanced or metastatic HER2- Breast Cancer (IHC 0, 1+, or 2+/ISH-). Participating patients were treated a 2.5 mg/kg D1D8 Q3W. They were not selected for EGFR or HER3 expression levels.
Additional subgroup analysis in previously disclosed data at SABCS 2024 shows encouraging efficacy with a manageable safety profile for izalontamab brengitecan in heavily pre-treated advanced or metastatic across all HER2 levels in HER2-breast cancer patients including HER2 0 patients. These data highlights continued progress in izalontamab brengitecan clinical development and builds upon the previously reported clinical data in breast cancer patients at SABCS in 2024.
“These data continue to support our conviction that izalontamab brengitecan demonstrates strong clinical efficacy across a wide variety of tumors such as breast cancer including HER2 negative breast cancer with a manageable safety profile,” said Jonathan Cheng, M.D., CMO of SystImmune.
“This positions izalontamab brengitecan as an important therapeutic option that may address the unmet medical needs of patients with limited treatment options,” Cheng said.
We are committed to advancing this therapy through clinical trials, exploring its potential not only as a monotherapy but also in combination with other agents, so as to improve outcomes for cancer patients globally,” he concluded.
Presentations at ESMO Breast 2025
- Title: Phase I study of iza-bren (BL-B01D1), an EGFR x HER3 Bispecific Antibody-drug Conjugate (ADC), in Patients with Locally Advanced or Metastatic Breast Cancer (BC)
- Presentation Number: 302MO
- Session Title: Mini Oral Session 2
- Speaker: Yiqun Du (Shanghai, China)
- Co-Authors: Jian Zhang (Shanghai, China), Jiong Wu (Shanghai, China), Yiqun Du (Shanghai, China), Yanchun Meng (Shanghai, China), Sa Xiao (Chengdu, China), Hai Zhu (Redmond, United States of America), Yi Zhu (Chengdu, China)
- Session Date & Time: Friday, May 16th, 2025, 8:20 AM-10:10 AM CEST
- Location: Room 1, ICM – International Congress Center Munich, Munich, Germany
__
Clinical trials
A Study of BL-B01D1 in Patients With Unresectable Locally Advanced or Metastatic Breast Cancer and Other Solid Tumors – ClinicalTrials.gov ID NCT05470348
A Study of Izalontamab Brengitecan Versus Chemotherapy in Participants With Previously Untreated, Locally Advanced, Recurrent Inoperable, or Metastatic Triple-negative Breast Cancer Ineligible for Anti-PD(L)1 Drugs (IZABRIGHT-Breast01)
ClinicalTrials.gov ID NCT06926868
Reference
[1] Ma Y, Huang Y, Zhao Y, Zhao S, Xue J, Yang Y, Fang W, Guo Y, Han Y, Yang K, Li Y, Yang J, Fu Z, Chen G, Chen L, Zhou N, Zhou T, Zhang Y, Zhou H, Liu Q, Zhu Y, Zhu H, Xiao S, Zhang L, Zhao H. BL-B01D1, a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study. Lancet Oncol. 2024 Jul;25(7):901-911. doi: 10.1016/S1470-2045(24)00159-1. Epub 2024 May 29. PMID: 38823410.
[2] Garcia D. SABC: Updated Data of Izalontamab Brengitecan/BL-B01D1 in Breast Cancer [Article]
This article was first published in ADC Review | J. Antibody-drug Conjugates on May 9, 2025
Featured image: Munich, Munich, Germany. Photo courtesy: © 2023 – 2025 Bayern Lens.use under the Unsplash License
DOI
