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Article: Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial

TitleEfficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial
Authors
KeywordsBintrafusp alfa
Correlative biomarkers
Efficacy
Recurrent or metastatic nasopharyngeal cancer
Safety
Issue Date1-Sep-2023
PublisherElsevier
Citation
The Lancet Regional Health - Western Pacific, 2023, v. 40 How to Cite?
Abstract

Background: The strategy of dual blockade of TGF-β and PD-L1 pathways has not been previously tested in platinum-refractory recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients. This study aimed to evaluate the safety and efficacy of bintrafusp alfa in refractory R/M NPC patients. Methods: In this single-arm, single-centre phase II clinical trial, 38 histologically confirmed R/M NPC patients were enrolled and administered with bintrafusp alfa every 2 weeks. Primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Findings: Thirty-eight patients were accrued (33 men; median age, 54 years). ORR was 23.7% (complete response, n = 2; partial response, n = 7). The median DOR was 19.2 months, median PFS was 2.3 months, median OS was 17.0 months, and 1-year OS rate was 63.2%. Unfortunately, 25 patients (65.7%) progressed within 8 weeks of treatment, 15 patients (39.5%) and 8 patients (21.1%) developed hyper-progressive disease (HPD) per RECIST v1.1 and tumor growth rate (TGR) ratio respectively. Sixteen patients (42.4%) experienced ≥ grade 3 treatment-related adverse events (TRAEs), most commonly anemia (n = 9, 23.7%) and secondary malignancies (n = 4, 10.5%). TRAEs led to permanent treatment discontinuation in 7 patients. Patients with strong suppression of plasma TGFβ1 level at week 8 were unexpectedly associated with worse ORR (9.1% vs 44.4%, P = 0.046) and development of HPD. There was no correlation between PD-L1 expression and ORR. Interpretation: Bintrafusp alfa demonstrated modest activity in R/M NPC but high rates of HPD and treatment discontinuation secondary to TRAEs are concerning. Funding: The project was supported by Alice Ho Miu Ling Nethersole Charity Foundation Professorship Endowed Fund and Merck KGaA.


Persistent Identifierhttp://hdl.handle.net/10722/332014
ISSN
2023 Impact Factor: 7.6
2023 SCImago Journal Rankings: 2.197
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChiang, Chi Leung-
dc.contributor.authorLam, Tai Chung-
dc.contributor.authorLi, James Chun Bong-
dc.contributor.authorChan, Kenneth Sik Kwan-
dc.contributor.authorEl Helali, Aya-
dc.contributor.authorLee, Yolanda Yim Ping-
dc.contributor.authorLaw, Laalaa Hiu Ting-
dc.contributor.authorZheng, Danyang-
dc.contributor.authorLo, Anthony Wing Ip-
dc.contributor.authorKam, Ngar Woon-
dc.contributor.authorLi, Wing Sum-
dc.contributor.authorCheung, Alice Ka Wai-
dc.contributor.authorChow, James Chung Hang-
dc.contributor.authorChan, Sunny Po Chung-
dc.contributor.authorLai, Jessica Wing Yu-
dc.contributor.authorLee, Sarah Wai Man-
dc.contributor.authorKong, Feng-Ming Spring-
dc.contributor.authorNg, Wai Tong-
dc.contributor.authorKwong, Dora Lai Wan-
dc.contributor.authorLee, Anne Wing Mui-
dc.date.accessioned2023-09-28T05:00:15Z-
dc.date.available2023-09-28T05:00:15Z-
dc.date.issued2023-09-01-
dc.identifier.citationThe Lancet Regional Health - Western Pacific, 2023, v. 40-
dc.identifier.issn2666-6065-
dc.identifier.urihttp://hdl.handle.net/10722/332014-
dc.description.abstract<p>Background: The strategy of dual blockade of TGF-β and PD-L1 pathways has not been previously tested in platinum-refractory recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients. This study aimed to evaluate the safety and efficacy of bintrafusp alfa in refractory R/M NPC patients. Methods: In this single-arm, single-centre phase II clinical trial, 38 histologically confirmed R/M NPC patients were enrolled and administered with bintrafusp alfa every 2 weeks. Primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Findings: Thirty-eight patients were accrued (33 men; median age, 54 years). ORR was 23.7% (complete response, n = 2; partial response, n = 7). The median DOR was 19.2 months, median PFS was 2.3 months, median OS was 17.0 months, and 1-year OS rate was 63.2%. Unfortunately, 25 patients (65.7%) progressed within 8 weeks of treatment, 15 patients (39.5%) and 8 patients (21.1%) developed hyper-progressive disease (HPD) per RECIST v1.1 and tumor growth rate (TGR) ratio respectively. Sixteen patients (42.4%) experienced ≥ grade 3 treatment-related adverse events (TRAEs), most commonly anemia (n = 9, 23.7%) and secondary malignancies (n = 4, 10.5%). TRAEs led to permanent treatment discontinuation in 7 patients. Patients with strong suppression of plasma TGFβ1 level at week 8 were unexpectedly associated with worse ORR (9.1% vs 44.4%, P = 0.046) and development of HPD. There was no correlation between PD-L1 expression and ORR. Interpretation: Bintrafusp alfa demonstrated modest activity in R/M NPC but high rates of HPD and treatment discontinuation secondary to TRAEs are concerning. Funding: The project was supported by Alice Ho Miu Ling Nethersole Charity Foundation Professorship Endowed Fund and Merck KGaA.<br></p>-
dc.languageeng-
dc.publisherElsevier-
dc.relation.ispartofThe Lancet Regional Health - Western Pacific-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectBintrafusp alfa-
dc.subjectCorrelative biomarkers-
dc.subjectEfficacy-
dc.subjectRecurrent or metastatic nasopharyngeal cancer-
dc.subjectSafety-
dc.titleEfficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial-
dc.typeArticle-
dc.identifier.doi10.1016/j.lanwpc.2023.100898-
dc.identifier.scopuseid_2-s2.0-85170274292-
dc.identifier.volume40-
dc.identifier.isiWOS:001071024700001-
dc.identifier.issnl2666-6065-

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