BMS-partnered iza-bren becomes world’s first approved bispecific ADC with China NPC nod

Edited by Robert McTiernan··3 min read

China has issued a market approval for iza-bren (izalontamab brengitecan; BL-B01D1) as a treatment for nasopharyngeal carcinoma (NPC), marking the first regulatory clearance globally for a bispecific antibody-drug conjugate (ADC) of any kind — a milestone that extends beyond NPC to validate a broader class of dual-targeting ADC constructs. China’s National Medical Products Administration (NMPA) gave the nod to Sichuan Biokin Pharmaceutical (Biokin) for iza-bren in patients with recurrent or metastatic NPC who have progressed following platinum-based chemotherapy and PD-1/PD-L1 inhibitor therapy.

While the China indication covers recurrent or metastatic NPC, the broader significance lies in the first commercial validation of a dual-targeting ADC architecture. The milestone is also important for Bristol Myers Squibb, which licensed ex-China rights to the asset from SystImmune in a 2023 deal valued at up to USD 8.4 billion. The approval therefore represents the first regulatory validation of both the molecule and the broader bispecific ADC strategy underpinning that partnership.

Unlike conventional ADCs, which recognize a single tumor-associated antigen, bispecific ADCs are designed to engage two targets simultaneously, potentially improving tumor selectivity, overcoming antigen heterogeneity, and expanding the addressable patient population. Iza-bren simultaneously targets EGFR and HER3, two receptor tyrosine kinases frequently co-expressed in epithelial cancers including NPC. The bispecific antibody component blocks downstream proliferation and survival signaling from both receptors, while internalization delivers a topoisomerase I inhibitor (Topo1i) payload — brengitecan — directly into tumor cells, inducing cytotoxic DNA damage. This dual-antigen engagement strategy is intended to improve tumor cell selectivity relative to monospecific ADCs targeting either receptor alone.

Approval was based on the pivotal Phase III BL-B01D1-303 study (NCT06118333), a randomized, open-label, multicenter trial conducted in China. In patients with recurrent or metastatic NPC who had failed prior PD-1/PD-L1 therapy and at least two lines of chemotherapy, iza-bren demonstrated a blinded independent central review-assessed confirmed objective response rate (ORR) of 54.6%, compared with 27.0% for physician’s choice of chemotherapy (odds ratio 3.3; 95% CI 1.9–5.8; p<0.0001). Median progression-free survival was 8.38 months versus 4.34 months for chemotherapy (hazard ratio 0.44; 95% CI 0.32–0.62). Overall survival data were immature at the time of analysis.

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NPC is geographically concentrated in southern China, Southeast Asia, and parts of North Africa, and is strongly associated with Epstein-Barr virus infection. For patients whose disease progresses after platinum-based chemotherapy and immunotherapy, prognosis is poor, with five-year overall survival rates generally below 10%. No ADC had previously been approved in this setting, and approved options in later lines remain limited, making the ORR and PFS improvements reported in BL-B01D1-303 clinically relevant for this population.

Washington-based SystImmune – a subsidiary of Biokin – is developing iza-bren in collaboration with Bristol Myers Squibb outside of China, where the asset is being advanced across multiple solid tumor indications. The approval establishes the first commercial proof point for the bispecific ADC modality and will be closely watched by developers pursuing next-generation ADC architectures across a range of solid tumor indications.

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