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.
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| Title: | 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. |
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| Authors: | Yang, Yunpeng (AUTHOR), Zhou, Huaqiang (AUTHOR), Tang, Linquan (AUTHOR), Qiu, Sufang (AUTHOR), Han, Yaqian (AUTHOR), Ji, Dongmei (AUTHOR), Chen, Xiaozhong (AUTHOR), Lei, Feng (AUTHOR), Qu, Song (AUTHOR), Deng, Bin (AUTHOR), Chen, Lusi (AUTHOR), Huang, Jianli (AUTHOR), Guo, Ye (AUTHOR), Liu, Zhigang (AUTHOR), Chen, Dongping (AUTHOR), Li, Jingao (AUTHOR), Shu, Xiaolei (AUTHOR), Qin, Yan (AUTHOR), Fu, Zhichao (AUTHOR), Li, Bihui (AUTHOR) |
| Source: | Lancet. Nov2025, Vol. 406 Issue 10516, p2235-2243. 9p. |
| Subjects: | Nasopharynx cancer, Antibody-drug conjugates, Epidermal growth factor receptors, Bispecific antibodies, Clinical trials, Cancer chemotherapy |
| Geographic Terms: | China |
| Abstract: | People with recurrent or metastatic nasopharyngeal carcinoma that progressed after chemotherapy and programmed cell death protein 1 (PD-1) and its ligand (PD-L1) inhibitors have few treatment options and a poor prognosis. We therefore aimed to investigate the efficacy and safety of the bispecific antibody–drug conjugate izalontamab brengitecan (iza-bren) in heavily pretreated individuals with recurrent or metastatic nasopharyngeal carcinoma. This multicentre, randomised, open-label, phase 3 study was conducted at 55 hospitals in China. Eligible participants were aged 18–75 years with histologically or cytologically confirmed recurrent or metastatic nasopharyngeal carcinoma that had progressed after at least two lines of systemic chemotherapy including at least one platinum-containing regimen and PD-1 or PD-L1 inhibitors. Participants were randomly assigned (1:1) to receive either iza-bren at 2·5 mg/kg intravenously on days 1 and 8 of each 3-week cycle or chemotherapy. Random assignment was done through an interactive web-based response system, stratified by baseline Eastern Cooperative Oncology Group performance status (0 vs 1), liver metastases, and previous lines of platinum-based chemotherapy (one line vs two or more lines), with a variable block size. The dual primary efficacy endpoints were objective response rate (ORR) assessed by masked independent central review as per Response Evaluation Criteria in Solid Tumours version 1.1 criteria, and overall survival. Progression-free survival, duration of response, and safety were the secondary endpoints. This report is the first planned interim analysis. This trial is registered with ClinicalTrials.gov (NCT06118333) and is ongoing. From Dec 4, 2023, to Feb 21, 2025, 522 patients were screened, of whom 386 were enrolled and randomly assigned to receive either iza-bren (n=191) or chemotherapy (n=195). At a median follow-up of 7·66 months for the iza-bren group and 7·10 months for the chemotherapy group, the ORR by masked independent central review was 54·6% (95% CI 45·2–63·8%) with iza-bren and 27·0% (19·1–36·0%) with chemotherapy (difference 27·9%, 95% CI 15·5–39·4%; p<0·0001). Overall survival data were not mature at data cutoff. Grade 3 or higher treatment-related adverse events occurred in 80% of patients receiving iza-bren and 62% of those receiving chemotherapy. The most common grade 3 or higher treatment-related adverse events in the iza-bren group were haematological, including anaemia (50% vs 10%), decreased white blood cell count (43% vs 44%), decreased platelet count (43% vs 7%), and decreased neutrophil count (38% vs 41%). Non-haematological treatment-related adverse events in the iza-bren group were mostly grade 1 or 2. Serious treatment-related adverse events occurred in 43% of patients receiving iza-bren and 27% of those receiving chemotherapy. Four (2%) treatment-related deaths occurred in the iza-bren group. Iza-bren significantly improved the ORR 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. Baili-Bio (Chengdu) Pharmaceutical. [ABSTRACT FROM AUTHOR] |
| Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 189149240 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: 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. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Yang%2C+Yunpeng%22">Yang, Yunpeng</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhou%2C+Huaqiang%22">Zhou, Huaqiang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tang%2C+Linquan%22">Tang, Linquan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Qiu%2C+Sufang%22">Qiu, Sufang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Han%2C+Yaqian%22">Han, Yaqian</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ji%2C+Dongmei%22">Ji, Dongmei</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Xiaozhong%22">Chen, Xiaozhong</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lei%2C+Feng%22">Lei, Feng</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Qu%2C+Song%22">Qu, Song</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Deng%2C+Bin%22">Deng, Bin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Lusi%22">Chen, Lusi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Huang%2C+Jianli%22">Huang, Jianli</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Guo%2C+Ye%22">Guo, Ye</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Zhigang%22">Liu, Zhigang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Dongping%22">Chen, Dongping</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Jingao%22">Li, Jingao</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shu%2C+Xiaolei%22">Shu, Xiaolei</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Qin%2C+Yan%22">Qin, Yan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fu%2C+Zhichao%22">Fu, Zhichao</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Bihui%22">Li, Bihui</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. Nov2025, Vol. 406 Issue 10516, p2235-2243. 9p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Nasopharynx+cancer%22">Nasopharynx cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Antibody-drug+conjugates%22">Antibody-drug conjugates</searchLink><br /><searchLink fieldCode="DE" term="%22Epidermal+growth+factor+receptors%22">Epidermal growth factor receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Bispecific+antibodies%22">Bispecific antibodies</searchLink><br /><searchLink fieldCode="DE" term="%22Clinical+trials%22">Clinical trials</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+chemotherapy%22">Cancer chemotherapy</searchLink> – Name: SubjectGeographic Label: Geographic Terms Group: Su Data: <searchLink fieldCode="DE" term="%22China%22">China</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: People with recurrent or metastatic nasopharyngeal carcinoma that progressed after chemotherapy and programmed cell death protein 1 (PD-1) and its ligand (PD-L1) inhibitors have few treatment options and a poor prognosis. We therefore aimed to investigate the efficacy and safety of the bispecific antibody–drug conjugate izalontamab brengitecan (iza-bren) in heavily pretreated individuals with recurrent or metastatic nasopharyngeal carcinoma. This multicentre, randomised, open-label, phase 3 study was conducted at 55 hospitals in China. Eligible participants were aged 18–75 years with histologically or cytologically confirmed recurrent or metastatic nasopharyngeal carcinoma that had progressed after at least two lines of systemic chemotherapy including at least one platinum-containing regimen and PD-1 or PD-L1 inhibitors. Participants were randomly assigned (1:1) to receive either iza-bren at 2·5 mg/kg intravenously on days 1 and 8 of each 3-week cycle or chemotherapy. Random assignment was done through an interactive web-based response system, stratified by baseline Eastern Cooperative Oncology Group performance status (0 vs 1), liver metastases, and previous lines of platinum-based chemotherapy (one line vs two or more lines), with a variable block size. The dual primary efficacy endpoints were objective response rate (ORR) assessed by masked independent central review as per Response Evaluation Criteria in Solid Tumours version 1.1 criteria, and overall survival. Progression-free survival, duration of response, and safety were the secondary endpoints. This report is the first planned interim analysis. This trial is registered with ClinicalTrials.gov (NCT06118333) and is ongoing. From Dec 4, 2023, to Feb 21, 2025, 522 patients were screened, of whom 386 were enrolled and randomly assigned to receive either iza-bren (n=191) or chemotherapy (n=195). At a median follow-up of 7·66 months for the iza-bren group and 7·10 months for the chemotherapy group, the ORR by masked independent central review was 54·6% (95% CI 45·2–63·8%) with iza-bren and 27·0% (19·1–36·0%) with chemotherapy (difference 27·9%, 95% CI 15·5–39·4%; p<0·0001). Overall survival data were not mature at data cutoff. Grade 3 or higher treatment-related adverse events occurred in 80% of patients receiving iza-bren and 62% of those receiving chemotherapy. The most common grade 3 or higher treatment-related adverse events in the iza-bren group were haematological, including anaemia (50% vs 10%), decreased white blood cell count (43% vs 44%), decreased platelet count (43% vs 7%), and decreased neutrophil count (38% vs 41%). Non-haematological treatment-related adverse events in the iza-bren group were mostly grade 1 or 2. Serious treatment-related adverse events occurred in 43% of patients receiving iza-bren and 27% of those receiving chemotherapy. Four (2%) treatment-related deaths occurred in the iza-bren group. Iza-bren significantly improved the ORR 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. Baili-Bio (Chengdu) Pharmaceutical. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/S0140-6736(25)01954-3 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 9 StartPage: 2235 Subjects: – SubjectFull: Nasopharynx cancer Type: general – SubjectFull: Antibody-drug conjugates Type: general – SubjectFull: Epidermal growth factor receptors Type: general – SubjectFull: Bispecific antibodies Type: general – SubjectFull: Clinical trials Type: general – SubjectFull: Cancer chemotherapy Type: general – SubjectFull: China Type: general Titles: – TitleFull: 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. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Yang, Yunpeng – PersonEntity: Name: NameFull: Zhou, Huaqiang – PersonEntity: Name: NameFull: Tang, Linquan – PersonEntity: Name: NameFull: Qiu, Sufang – PersonEntity: Name: NameFull: Han, Yaqian – PersonEntity: Name: NameFull: Ji, Dongmei – PersonEntity: Name: NameFull: Chen, Xiaozhong – PersonEntity: Name: NameFull: Lei, Feng – PersonEntity: Name: NameFull: Qu, Song – PersonEntity: Name: NameFull: Deng, Bin – PersonEntity: Name: NameFull: Chen, Lusi – PersonEntity: Name: NameFull: Huang, Jianli – PersonEntity: Name: NameFull: Guo, Ye – PersonEntity: Name: NameFull: Liu, Zhigang – PersonEntity: Name: NameFull: Chen, Dongping – PersonEntity: Name: NameFull: Li, Jingao – PersonEntity: Name: NameFull: Shu, Xiaolei – PersonEntity: Name: NameFull: Qin, Yan – PersonEntity: Name: NameFull: Fu, Zhichao – PersonEntity: Name: NameFull: Li, Bihui IsPartOfRelationships: – BibEntity: Dates: – D: 08 M: 11 Text: Nov2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 01406736 Numbering: – Type: volume Value: 406 – Type: issue Value: 10516 Titles: – TitleFull: Lancet Type: main |
| ResultId | 1 |
