The Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has approved izalontamab brengitecan (iza-bren; formerly BL-B01D1) for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) whose disease has progressed following prior platinum-based chemotherapy and PD-1/PD-L1-directed therapies.

This approval makes iza-bren the world's first approved bispecific antibody-drug conjugate (BsADC), marking the transition from single-target ADCs to next-generation dual-target precision therapeutics.

Why BsADCs?

ADCs are a key therapeutic modality in targeted cancer treatment, which combine the precision of monoclonal antibodies with the potency of cytotoxic drugs. With 23 global approvals, ADCs generated ~$16 billion in 2025. Despite the substantial clinical success of ADC monotherapy, ADCs still face challenges such as limited response rates, acquired resistance, and immune evasion.

BsADCs represent further opportunities in this field by leveraging bispecific antibodies that simultaneously bind two distinct targets, potentially improving tumor selectivity, internalization efficiency, and therapeutic efficacy while reducing systemic toxicity.

​

Figure 1: The concept and design considerations of BsADCs. Reference [1]

Izalontamab brengitecan (iza-bren) - The First Approved BsADC

Izalontamab brengitecan (BL-B01D1, Iza-bren) is a first-in-class EGFR/HER3 bispecific ADC developed by SystImmune and partnered with Bristol Myers Squibb outside China. Iza-bren is designed to simultaneously target EGFR and HER3, two receptors frequently expressed in various epithelial cancers and implicated in tumor proliferation and survival. Following dual-target binding and receptor-mediated internalization, Iza-bren releases a proprietary topoisomerase I inhibitor (Topo1i) payload inside tumor cells, resulting in DNA damage and cell death. By combining dual-target blockade with targeted payload delivery, Iza-bren aims to enhance tumor selectivity and antitumor activity compared with conventional single-target ADCs.

The FDA approval is supported by the positive results from BL-B01D1-303 study (NCT06118333), the world’s first confirmatory Phase III clinical trial for the late-line treatment of NPC. Clinical data demonstrated that iza-bren doubled the therapeutic efficacy compared to standard chemotherapy regimens (gemcitabine, capecitabine, or docetaxel), achieving the following:

• ● Confirmed objective response rate (cORR) of 54.6% vs. 27.0% for chemotherapy
• ● Median duration of response (DoR) of 8.5 months vs. 4.8 months for physician's choice of chemotherapy
• ● Median progression-free survival (PFS) of 8.38 months vs. 4.34 months for chemotherapy
• ● Median overall survival (mOS) not yet reached

As of June 2026, iza-bren is involved in over 40 cross-tumor clinical trials in the US and China, accumulating 8 breakthrough therapy designations. At ASCO® 2026, Iza-bren has presented  positive results from prespecified interim analyses of two Phase 3 studies - PANKU-Breast02 (BL-B01D1-307) and PANKU-Esophagus01 (BL-B01D1-305) .

PANKU-Breast02: Triple-Negative Breast Cancer (TNBC)

The Phase 3 PANKU-Breast02 trial compared iza-bren to physician’s choice of chemotherapy (TPC) in patients with advanced TNBC. The trial successfully met its dual primary endpoints for overall survival (OS) and progression-free survival (PFS).

• ● Median OS: 15.9 months (iza-bren) vs. 12.5 months (TPC); HR: 0.60 (p=0.0019).
• ● Median PFS (BICR): 8.5 months (iza-bren) vs. 3.1 months (TPC); HR: 0.29 (p<0.0001).
• ● Confirmed ORR (BICR): 51.7% (iza-bren) vs. 20.5% (TPC).

PANKU-Esophagus01: Esophageal Squamous Cell Carcinoma (ESCC)

The Phase 3 PANKU-Esophagus01 trial evaluated iza-bren against physician’s choice of chemotherapy in patients with recurrent or metastatic ESCC. The study achieved statistically significant improvements in both OS and PFS.

• ● Median OS: 9.8 months (iza-bren) vs. 7.2 months (chemotherapy); HR: 0.64 (p=0.0004).
• ● Median PFS (BICR): 4.2 months (iza-bren) vs. 2.0 months (chemotherapy); HR: 0.50 (p<0.0001).
• ● ORR (BICR): 35.3% (iza-bren) vs. 13.1% (chemotherapy).

Bispecific ADCs in Clinical Development

The success of iza-bren has opened the floodgates for bsADCs. Currently, over 100 bsADCs are in clinical stages.

Table: Global Bispecific ADCs in Clinical Trials (2026)

Conclusion

The first approval of a bispecific ADC signals a new phase in ADC development. While traditional ADCs have already established their value in oncology, bispecific formats offer additional opportunities to enhance tumor selectivity, improve internalization, and broaden therapeutic activity across heterogeneous tumors. With multiple late-stage candidates now advancing through clinical development, the coming years will provide a clearer view of how broadly this approach can be applied across cancer indications.

Alongside advances in antibodies and payloads, linker design remains a critical component of ADC optimization. PEG-based linkers continue to play an important role in improving molecular properties and drug delivery performance. Biopharma PEG provides a range of PEG linker technologies and customized PEG derivatives that support the development of next-generation ADCs and other targeted bioconjugates.

References:
[1] Gu Y, Wang Z, Wang Y. Bispecific antibody drug conjugates: Making 1+1>2. Acta Pharm Sin B. 2024 May;14(5):1965-1986. doi: 10.1016/j.apsb.2024.01.009. Epub 2024 Jan 20. PMID: 38799638; PMCID: PMC11119582.
[2] SystImmune Announces First Approval of Iza-bren for the Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma in China https://www.prnewswire.com/news-releases/systimmune-announces-first-approval-of-iza-bren-for-the-treatment-of-recurrent-or-metastatic-nasopharyngeal-carcinoma-in-china-302806766.html 
[3] Izalontamab Brengitecan (Iza-Bren) Demonstrates Statistically Significant and Clinically Meaningful Improvements in Overall Survival and Progression-Free Survival in Patients with Triple-Negative Breast Cancer and Esophageal Squamous Cell Carcinoma https://news.bms.com/news/corporate-financial/2026/Izalontamab-Brengitecan-Iza-Bren-Demonstrates-Statistically-Significant-and-Clinically-Meaningful-Improvements-in-Overall-Survival-and-Progression-Free-Survival-in-Patients-with-Triple-Negative-Breast-Cancer-and-Esophageal-Squamous-Cell-Carcinoma/default.aspx