In an interim analysis of a Chinese phase III trial (BL-B01D1-303) reported in The Lancet, Yang et al found that izalontamab brengitecan (iza-bren)—a bispecific antibody–drug conjugate targeting EGFR and HER3—significantly improved the objective response rate vs physician’s choice of chemotherapy in patients with heavily pretreated recurrent or metastatic nasopharyngeal carcinoma.
Study Details
In the multicenter open-label trial, 388 patients whose disease had progressed after at least two lines of systemic chemotherapy (including at least one platinum-containing regimen and PD-1/PD-L1 inhibitor) were randomly assigned between December 2023 and February 2025 to receive iza-bren at 2.5 mg/kg on days 1 and 8 of each 3-week cycle (n = 191) or physician's choice of chemotherapy (n = 195); chemotherapy choices consisted of any one of the following: capecitabine at 1,000 mg/m² twice per day on days 1 to 14 in each 3-week cycle; gemcitabine at 1,000 mg/m² on days 1 and 8 of each 3-week cycle; or docetaxel at 75 mg/m² once every 3 weeks. The dual primary endpoints are objective response rate on masked independent central review and overall survival.
Key Findings
At a median follow-up of 7.66 months in the iza-bren group and 7.10 months in the chemotherapy group, objective response rates were 54.6% (95% confidence interval [CI] = 45.2%–63.8%) in the iza-bren group vs 27.0% (95% CI = 19.1%–36.0%) in the chemotherapy group (odds ratio = 3.33, 95% CI = 1.91–5.80, P < .0001). Complete response was observed in one patient in the iza-bren group. Median duration of response was 8.51 months (95% CI = 6.97 months to not reached) vs 4.76 months (95% CI = 4.04–6.93 months).
Median progression-free survival was 8.38 vs 4.34 months (hazard ratio = 0.44, 95% CI = 0.32–0.62); rates at 6 and 9 months were 83.4% vs 66.6% and 60.9% vs 29.1%. Overall survival data were not mature.
Grade 3 or higher treatment-related adverse events occurred in 80% of the iza-bren group vs 62% of the chemotherapy group. The most common in the iza-bren group were hematologic, including anemia (50% vs 10% in the chemotherapy group), decreased white blood cell count (43% vs 44%), decreased platelet count (43% vs 7%), and decreased neutrophil count (38% vs 41%). Serious treatment-related adverse events occurred in 43% vs 27% of patients. Treatment-related adverse events led to death in four patients, all in the iza-bren group, including two due to febrile neutropenia.
The investigators concluded: “Iza-bren significantly improved the [objective response rate] compared with chemotherapy in individuals with heavily pretreated recurrent or metastatic nasopharyngeal carcinoma, with a manageable safety profile. These findings suggest iza-bren might represent a new therapeutic standard for this population. Further analysis will help to fully understand the benefit of this new therapy.”
Li Zhang, MD, of Sun Yat-sen University Cancer Center, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Baili-Bio (Chengdu) Pharmaceutical. For full disclosures of all study authors, visit thelancet.com.
