BMS-backed bispecific achieves Phase III success in nasopharyngeal cancer

Bristol Myers Squibb's significant investment of $8.4 billion in Chinese-developed antibody-drug conjugates (ADCs) is beginning to yield promising results. Partnering with Sichuan Biokin Pharmaceutical, the experimental therapy izalontamab brengitecan (iza-bren; BL-B01D1) has demonstrated success in a Phase III trial targeting advanced nasopharyngeal carcinoma. This achievement, announced through a regulatory filing, marks a significant clinical breakthrough for the innovative ADC, which aims at both EGFR and HER3 proteins.

The clinical study, known as BL-B01D1-303, involved 386 participants suffering from recurrent or metastatic nasopharyngeal carcinoma. These patients had previously undergone at least two rounds of platinum-based chemotherapy, after which they received PD-1/PD-L1 monoclonal antibody therapy as a final treatment option. The interim results were disclosed approximately 18 months after the trial commenced towards the end of 2023.

Bristol Myers Squibb (BMS) acquired the rights to market iza-bren outside China in December 2023, committing $800 million upfront to Biokin's American subsidiary, SystImmune. The agreement has the potential to reach a valuation of $8.4 billion, contingent upon the drug achieving specific milestones, including $500 million linked to immediate clinical advancements. Additional details about the financial arrangement were revealed in a Hong Kong Stock Exchange filing earlier this year. Notably, BMS is required to pay $250 million if a Phase II or III trial begins for first- or second-line patients in the United States by the end of 2025, with an additional $250 million payable if a first-line Phase III trial launches by the end of 2026.

Biokin disclosed that iza-bren is currently under investigation in over 40 studies across various cancer types, predominantly in China, but also extending to the United States. In December of the previous year, BMS initiated a Phase I/IIa trial in the U.S. to evaluate iza-bren in combination with AstraZeneca's Tagrisso (osimertinib) or Merck & Co.'s Keytruda (pembrolizumab) for advanced solid tumors.

Furthermore, BMS is preparing to launch the Phase II/III IZABRIGHT-Breast01 trial. This study aims to compare the efficacy of iza-bren against chemotherapy in patients with first-line metastatic triple-negative breast cancer or estrogen receptor-low/HER2-negative breast cancer. These patients are not viable candidates for anti-PD(L)1 therapy and endocrine treatments. The primary completion of this trial is anticipated in early 2028.

This venture into ADCs represents a strategic move by Bristol Myers Squibb, tapping into the potential of targeted cancer therapies developed in China. The promising clinical results thus far underscore the potential of iza-bren to transform treatment paradigms for challenging cancer types, particularly nasopharyngeal carcinoma, and possibly extending to other solid tumors. As research continues, the pharmaceutical industry closely watches the development and implications of ADC therapies in oncology.