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Patients treated with izalontamab brengitecan (iza-bren; BL-B01D1) had superior overall response rate (ORR) compared with chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC), according to results from the BL-B01D1-301 study (NCT06118333) presented at the 2025 European Society for Medical Oncology (ESMO) Congress and published in The Lancet.^1,2

The ORR by blinded independent central review was 54.6% (95% CI, 45.2%–63.8%) with iza-bren vs 27.0% (95% CI, 19.1%–36.0%) with chemotherapy, with an odds ratio of 3.3 (95% CI, 1.9–5.8; P < .0001) showing it was significantly higher in this primary end point.¹

“This was the first randomized phase 3 study evaluating iza-bren in recurrent or metastatic NPC. Our study has met its primary end point for ORR, and we can see a clinically meaningful improvement in progression-free survival [PFS] and it has a management safety profile,” said Huaqiang Zhou, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, in his presentation.¹

Approximately 20% to 30% of patients with NPC have recurrent or distant metastases, and current treatment options have low response rates. Iza-bren is a potentially first-in-class topoisomerase 1 inhibitor-based EGFR and HER3 bispecific antibody-drug conjugate (ADC).

The multicenter, randomized, open-label, phase 3 BL-B01D1-301 trial was designed to investigate this agent in patients who had previously received at least 2 lines of systemic chemotherapy including at least 1 platinum-containing regimen and a PD-1 or PD-L1 inhibitor. The primary end points were ORR and overall survival (OS), with secondary end points including progression-free survival, duration of response (DOR), and safety.

Patients were enrolled in 55 hospitals in China. They were stratified by number of prior lines of platinum-based treatment, ECOG performance status of 0 vs 1, and presence/absence of liver metastases.

Of 522 patients who were screened, 386 were randomly assigned on a 1:1 basis with 191 receiving 2.5 mg/kg iza-bren on days 1 and 8 of a 3-week cycle with 195 receiving physician’s choice of chemotherapy.¹

The median age of patients was 50.0 in the treatment arm and 49.0 in the chemotherapy arm, with the majority being male in each arm (85.3% and 81.0%, respectively). The majority had ECOG performance status of 1 (75.9% in both arms). Over half of patients in both arms had received 2 prior lines of therapy with the rest having received at least 3 lines. The majority had received 2 prior lines of chemotherapy, with 48.2% of each arm having received 2 prior lines of platinum-based chemotherapy. Prior radiotherapy had been used in 89.5% of the experimental arm and 88.2% of the control arm.

Metastases were present at baseline in the liver, bones, and lungs in 47.6%, 49.2%, and 46.6% of the experimental arm and 48.7%, 46.7%, and 37.4% of the control arm.

Results were reported at median follow-up of 7.66 months for iza-bren and 7.10 months for chemotherapy. There was 1 complete response in the iza-bren arm and none in the control arm. The disease control rate was 82.4% with iza-bren vs 69.6% with chemotherapy. All subgroups favored iza-bren in this analysis.

The median DOR was 8.5 months for iza-bren vs 4.8 months for physician’s choice of chemotherapy (HR, 0.43; 95% CI, 0.22–0.83). The median PFS was 8.38 months with iza-bren vs 4.34 months for chemotherapy (HR, 0.44; 95% CI, 0.32–0.62), and this trend was consistent across subgroups. At this time, OS was not mature.

Treatment-related adverse events (TRAEs) of grade 3 or higher were reported in 79.9% of patients receiving iza-bren vs 61.6% of those receiving chemotherapy. Serious TRAEs occurred in 43.4% of patients in the iza-bren arm vs 27.0% in the chemotherapy arm, and 4 (2%) treatment-related deaths occurred in the iza-bren group. Dose reductions due to TRAEs were needed in 41.8% with iza-bren vs 24.3% with chemotherapy, and TRAEs leading to dose interruption occurred in 61.4% vs 18.4%, respectively. TRAEs led to treatment discontinuation in 2.6% vs 3.2%, respectively.

Hematological AEs were reported more frequently with iza-bren vs chemotherapy including anemia in 50% vs 10% and decreased platelet count in 43% vs 7%. Decreased white blood cell count occurred in 43% vs 44% and decreased neutrophil count occurred in 38% vs 41%, respectively. According to Zhou, these were well managed by standard supportive care. The majority of nonhematologic TRAEs were grade 1 or 2, and no new safety signals were identified.

Two cases of grade 2 interstitial lung disease (ILD) occurred in the experimental arm and 2 cases of grade 3 ILD occurred in the chemotherapy arm.

“Based on this trial, iza-bren represents a potential new standard of care for heavily pretreated patients with recurrent or metastatic NPC,” concluded Zhou.

REFERENCES:

1. Yang Y, Zhou H, Tang L, et al. Iza-bren (BL-B01D1), an EGFR×HER3 bispecific antibody-drug conjugate, versus physician’s choice of chemotherapy in heavily pretreated recurrent/metastatic nasopharyngeal carcinoma: a randomized, open-label, multicenter, phase III, pivotal study (BL-B01D1-303). Presented at: 2025 European Society for Medical Oncology Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA35.

2. Yang Y, Zhou H, Tang L, et al. Izalontamab brengitecan, an EGFR and HER3 bispecific antibody–drug conjugate, versus chemotherapy in heavily pretreated recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 study in China. Lancet. Published online October 19, 2025. doi:10.1016/S0140-6736(25)01954-3