Iza-Bren (BL-B01D1): Bispecific EGFR/HER3 ADC Shows Promise in EGFR-Mutated NSCLC
Iza-Bren (BL-B01D1) is a bispecific EGFR/HER3 ADC for EGFR-mutated NSCLC. At IASLC WCLC 2025, Phase II combo with osimertinib showed 100% ORR and 92% 12-mo PFS; monotherapy in pretreated patients had 66% ORR and 80% 12-mo OS, with manageable safety.
Iza-Bren (BL-B01D1, Izalontamab Brengitecan) is a potential first-in-class bispecific antibody-drug conjugate (ADC) designed to target EGFR and HER3, aiming to overcome resistance mechanisms in EGFR-mutated non-small cell lung cancer (NSCLC). At the 2025 World Conference on Lung Cancer (WCLC) organized by IASLC, new Phase II and Phase I/II data highlighted its potential as both a first-line combination therapy with osimertinib and as monotherapy in pretreated patients.
Phase II Study: Iza-Bren + Osimertinib in First-Line EGFR-Mutated NSCLC
At IASLC WCLC 2025, a Phase II study presented compelling data on the combination of Iza-Bren and osimertinib in the first-line setting for patients with locally advanced or metastatic EGFR-mutated NSCLC.
Key Efficacy Findings (2.5 mg/kg cohort, n=40):
- Objective Response Rate (ORR): 100%, with a confirmed ORR of 95%.
- 12-Month Progression-Free Survival (PFS): 92.1%.
- Median Duration of Response (DoR): Not yet reached.
Safety Profile:
- Most treatment-related adverse events (TRAEs) were hematologic:
- Anemia: 91.9%
- Neutropenia: 91.1%
- Leukopenia: 91.1%
- Thrombocytopenia: 75.6%
- Non-hematologic TRAEs included nausea, stomatitis, decreased appetite, vomiting, diarrhea, and asthenia.
- Grade ≥3 events were manageable with supportive care and dose adjustments.
- Discontinuation rate due to TRAEs: 13.0%.
Interpretation: These results suggest that the Iza-Bren + osimertinib combination could represent a transformative first-line treatment option for patients with EGFR-mutant NSCLC.
Phase I/II Monotherapy Study in Previously Treated NSCLC
In a separate Phase I/II study presented at IASLC WCLC 2025, Iza-Bren was evaluated as a monotherapy in patients who had previously received EGFR-targeted therapy.
Key Outcomes (subgroup treated at 2.5 mg/kg D1D8 Q3W):
- Objective Response Rate (ORR): 66.0%, with a confirmed ORR (cORR) of 56.0%
- Median Progression-Free Survival (mPFS): 12.5 months
- Median Duration of Response (mDOR): 13.7 months
- 12-Month Overall Survival (OS) Rate: 80.3%
Safety Profile: Similar to the combination study, with manageable hematologic and non-hematologic TRAEs, demonstrating the tolerability of Iza-Bren monotherapy.
Comparative Overview: Phase II vs Phase I/II
| Study | Population | Treatment | ORR (Confirmed) | Median PFS | Median DoR | 12-Month OS | Key TRAEs | Discontinuation Rate |
|---|---|---|---|---|---|---|---|---|
| Phase II | First-line EGFR-mutated NSCLC (n=40) | Iza-Bren + Osimertinib 2.5 mg/kg | 100% (95%) | Not reached at 12 mo, 12-mo PFS 92.1% | Not yet reached | – | Hematologic: anemia 91.9%, neutropenia 91.1%, leukopenia 91.1%, thrombocytopenia 75.6% Non-hematologic: nausea, stomatitis, decreased appetite, vomiting, diarrhea, asthenia | 13.0% |
| Phase I/II | Previously treated EGFR-mutated NSCLC | Iza-Bren monotherapy | 66% (56%) | 12.5 mo | 13.7 mo | 80.3% | Similar hematologic/non-hematologic TRAEs as combo study | – |
Notes:
- ORR: Objective Response Rate
- PFS: Progression-Free Survival
- DoR: Duration of Response
- OS: Overall Survival
- TRAEs: Treatment-Related Adverse Events
Origins, Licensing, and Regulatory Status
- Developed By: SystImmune Inc., a U.S. subsidiary of Sichuan Biokin Pharmaceutical Co., Ltd.
- Licensing Agreement: In December 2023, Biokin Pharma entered into a global licensing and collaboration deal with Bristol Myers Squibb (BMS) valued at up to $8.4 billion, covering development and commercialization outside China.
- Regulatory Status: Iza-Bren has received Breakthrough Therapy Designation from the U.S. FDA for patients with previously treated advanced EGFR-mutated NSCLC.
Competitive Landscape and Implications
Iza-Bren enters a highly competitive space of next-generation EGFR-targeted therapies, including bispecific ADCs and combinations addressing EGFR resistance mechanisms. Its dual-target EGFR/HER3 approach and encouraging efficacy in both frontline and pretreated patients could position it as a potentially practice-changing therapy, pending confirmatory Phase III results.
Sources
- IASLC 2025 WCLC Abstracts – Iza-Bren Phase II combination study.
- IASLC 2025 WCLC Abstracts – Iza-Bren Phase I/II monotherapy study.
- Biokin Pharmaceutical Press Release, Dec 2023 – Global licensing agreement with BMS.
- U.S. FDA – Breakthrough Therapy Designation announcements.
Disclaimer: This article is for informational purposes only and does not constitute medical or investment advice. Readers should consult primary literature and official regulatory sources for verification.