At ESMO 2025, Huaqiang Zhou (Guangzhou, China) presented the Iza-Bren data during the Proffered Paper session on Developmental Therapeutics. He shared key insights from the preplanned interim analysis of BL-B01D1-303, a randomized phase III study testing the EGFR×HER3 bispecific antibody-drug conjugate against treatment/physician’s choice chemotherapy in heavily pretreated recurrent/metastatic nasopharyngeal carcinoma (R/M-NPC). The headline findings were higher objective response rate (ORR), longer progression-free survival (PFS), and more durable responses with Iza-Bren versus chemotherapy, alongside a manageable, mainly hematologic safety profile.
Introduction
Patients with R/M-NPC who progress after multiple lines of chemotherapy and PD-(L)1 inhibitors face limited options and poor prognosis. Iza-Bren, an EGFR×HER3 bispecific ADC, is designed to co-target two relevant receptors in NPC biology and deliver a cytotoxic payload to tumor cells. BL-B01D1-303 evaluates whether this dual-targeting ADC can outperform standard chemotherapy choices in late-line R/M-NPC.
Methods
This open-label, multicenter, randomized (1:1) phase III trial enrolled adults with R/M-NPC after ≥2 prior chemotherapy lines (including ≥1 platinum-based) and prior PD-(L)1 therapy. The preplanned interim analysis (IA)used a data cutoff of March 30, 2025. Between December 4, 2023 and February 21, 2025, 386 patients were randomized (Iza-Bren n=191; chemotherapy n=195). Dual primary endpoints were confirmed ORR (cORR; RECIST 1.1, blinded independent central review [BICR]) and overall survival (OS); duration of response (DoR), PFS, and safety were secondary endpoints. Median follow-up at IA was 7.66 vs 7.10 months for Iza-Bren and chemotherapy, respectively. ClinicalTrials.gov: NCT06118333.
Arms & dosing
- Iza-Bren: 2.5 mg/kg on day 1 and day 8 every 3 weeks
- Treatment/physician’s choice (TPC): capecitabine, gemcitabine, or docetaxel
Results
From Dec 4, 2023 to Feb 21, 2025, 386 patients were randomized (Iza-Bren n=191; TPC n=195). At the interim analysis (data cutoff Mar 30, 2025), median follow-up was 7.66 vs 7.10 months (Iza-Bren/TPC).
- cORR: 54.6% vs 27.0% (Iza-Bren vs TPC); odds ratio 3.33; P < .0001.
- Median DoR: 8.51 vs 4.76 months.
- Median PFS: 8.38 vs 4.34 months; HR 0.44 (95% CI 0.32–0.62).
- OS: Immature at IA.
- Grade ≥3 TRAEs: 79.9% (Iza-Bren) vs 61.6% (TPC).
Predominantly hematologic with Iza-Bren; non-hematologic events largely grade 1–2.
Take-home messages
- Iza-Bren more than doubled ORR and nearly doubled median PFS vs chemotherapy, with longer DoR.
- 56% lower risk of progression or death (HR 0.44).
- Higher grade ≥3 hematologic toxicity but manageable overall; requires proactive monitoring/supportive care.
- OS not mature—continued follow-up will define survival benefit and durability.
- If benefits persist with mature OS and QoL data, Iza-Bren is a strong candidate for a new standard in heavily pretreated R/M-NPC (NCT06118333).
The ESMO presentation was accompanied by a simultaneous online publication in The Lancet Oncology.
You can also read the Iza-Bren FDA Breakthrough Therapy Designation article on OncoDaily.
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