Iza-Bren Plus Pembrolizumab Shows Activity in Recurrent or Metastatic HNSCC

At the 2026 European Society for Medical Oncology (ESMO) Congress, Dongmei Ji, MD, of the Department of Medical Oncology at Fudan University Shanghai Cancer Center in China, presented phase 2 results for izalontamab brengitecan (iza-bren) plus pembrolizumab (Keytruda) during a rapid oral session on head and neck cancer.¹ The trial (NCT06437522) enrolled patients with previously untreated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). At the selected 2.5 mg/kg dose of iza-bren, the objective response rate (ORR) was 57.9% (95% CI, 40.8%-73.7%), and the median progression-free survival (PFS) was 8.5 months (95% CI, 4.4-15.0).

Iza-bren is a first-in-class antibody-drug conjugate (ADC). It links a bispecific antibody against EGFR and HER3, both of which are commonly expressed in HNSCC, to the topoisomerase I inhibitor Ed-04 through a cleavable linker.²

Stage 1 of the trial was a safety run-in in patients who had received prior treatment. In stage 2, the expansion phase, 84 patients with untreated disease were assigned to iza-bren at 2.5 mg/kg (n = 44) or 2.75 mg/kg (n = 40) on days 1 and 8 of each 3-week cycle. All patients also received pembrolizumab 200 mg every 3 weeks. The primary end points were ORR and the recommended phase 2 dose. Secondary end points included PFS, disease control rate (DCR), duration of response (DOR), and safety.

Among the 84 patients in stage 2, the median age was 56.0 years (range, 32.0-73.0), 94.0% were male, and 70.2% had distant metastases. The median sum of target lesion diameters was 41.6 mm (range, 11.5-150.0), and the most common primary site was the oral cavity (46.4%).

The efficacy analysis included 78 patients; 6 patients still on treatment had not yet reached their first post-baseline scan. As of the July 31, 2026, data cutoff, the median follow-up for overall survival (OS) was 16.7 months (95% CI, 15.9-18.3). In the 2.5 mg/kg cohort (n = 38), the ORR was 57.9% (95% CI, 40.8%-73.7%) and the confirmed ORR was 47.4% (95% CI, 31.0%-64.2%). The DCR was 81.6% (95% CI, 65.7%-92.3%), the median DOR was 13.6 months (95% CI, 6.5-not reached [NR]), and the median OS was NR (95% CI, 8.1-NR).

In the 2.75 mg/kg cohort (n = 40), the ORR was 62.5% (95% CI, 45.8%-77.3%) and the confirmed ORR was 50.0% (95% CI, 33.8%-66.2%). The DCR was 85.0% (95% CI, 70.2%-94.3%), the median DOR was 17.8 months (95% CI, 4.3-NR), the median PFS was 5.7 months (95% CI, 3.8-10.8), and the median OS was 19.3 months (95% CI, 11.7-NR).

Tumors shrank in 81.6% (n = 31/38) of patients at 2.5 mg/kg, with a median maximum shrinkage of 61.5% (range, 4.7%-100%). At 2.75 mg/kg, tumors shrank in 85.0% (n = 34/40), with a median maximum shrinkage of 48.2% (range, 10.8%-88.7%).

At 2.5 mg/kg, the confirmed ORR was 35.3% (95% CI, 14.2%-61.7%) in oral cavity tumors, 50.0% (95% CI, 15.7%-84.3%) in laryngeal tumors, and 37.5% (95% CI, 8.5%-75.5%) in hypopharyngeal tumors; the confirmed ORR was 100% (n = 2/2) in oropharyngeal tumors.

Across both doses, grade 3 or higher treatment-related adverse events (TRAEs) were mostly hematologic. They were managed with standard supportive care, including dose reductions. In all, 4.8% (n = 4/84) of patients discontinued treatment because of iza-bren–related AEs. Neutropenia led to dose reduction in 8.3% of patients and anemia in 3.6%, and each led to discontinuation in 1.2%. No cases of febrile neutropenia occurred. Infection-related AEs occurred in 22.6% of patients and were grade 3 or higher in 11.9%.

Three treatment-related deaths occurred, all at the 2.75 mg/kg dose: 1 each from sepsis, pneumonia, and septic shock. One grade 1 case of interstitial lung disease (ILD) also occurred at that dose. At 2.5 mg/kg, grade 3 or higher neutropenia occurred in 29.5% of patients and thrombocytopenia in 18.2%, and there were no ILD cases or treatment-related deaths.

Based on these findings, the investigators selected iza-bren at 2.5 mg/kg on days 1 and 8 every 3 weeks as the recommended phase 3 dose for the combination. A phase 3 study in China is being planned.

Disclosures

Ji reported no conflicts of interest. The study was sponsored by Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.

References

1. Ji D, Hu C, Liu Z, et al. Phase II study of izalontamab brengitecan (iza-bren) plus pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Presented at: 2026 European Society for Medical Oncology Congress; October 23-27, 2026; Madrid, Spain. Abstract 1542RO.
2. Ma Y, Huang Y, Zhao Y, et al. BL-B01D1, a first-in-class EGFR–HER3 bispecific antibody–drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study. Lancet Oncol. 2024;25(7):901-911. doi:10.1016/S1470-2045(24)00159-1