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Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial
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. METHOD...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493598/ https://www.ncbi.nlm.nih.gov/pubmed/37701718 http://dx.doi.org/10.1016/j.lanwpc.2023.100898 |
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author | Chiang, Chi Leung Lam, Tai Chung Li, James Chun Bong Chan, Kenneth Sik Kwan El Helali, Aya Lee, Yolanda Yim Ping Law, Laalaa Hiu Ting Zheng, Danyang Lo, Anthony Wing Ip Kam, Ngar Woon Li, Wing Sum Cheung, Alice Ka Wai Chow, James Chung Hang Chan, Sunny Po Chung Lai, Jessica Wing Yu Lee, Sarah Wai Man Kong, Feng-Ming (Spring) Ng, Wai Tong Kwong, Dora Lai Wan Lee, Anne Wing Mui |
author_facet | Chiang, Chi Leung Lam, Tai Chung Li, James Chun Bong Chan, Kenneth Sik Kwan El Helali, Aya Lee, Yolanda Yim Ping Law, Laalaa Hiu Ting Zheng, Danyang Lo, Anthony Wing Ip Kam, Ngar Woon Li, Wing Sum Cheung, Alice Ka Wai Chow, James Chung Hang Chan, Sunny Po Chung Lai, Jessica Wing Yu Lee, Sarah Wai Man Kong, Feng-Ming (Spring) Ng, Wai Tong Kwong, Dora Lai Wan Lee, Anne Wing Mui |
author_sort | Chiang, Chi Leung |
collection | PubMed |
description | 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 10.13039/100009945Merck KGaA. |
format | Online Article Text |
id | pubmed-10493598 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-104935982023-09-12 Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial Chiang, Chi Leung Lam, Tai Chung Li, James Chun Bong Chan, Kenneth Sik Kwan El Helali, Aya Lee, Yolanda Yim Ping Law, Laalaa Hiu Ting Zheng, Danyang Lo, Anthony Wing Ip Kam, Ngar Woon Li, Wing Sum Cheung, Alice Ka Wai Chow, James Chung Hang Chan, Sunny Po Chung Lai, Jessica Wing Yu Lee, Sarah Wai Man Kong, Feng-Ming (Spring) Ng, Wai Tong Kwong, Dora Lai Wan Lee, Anne Wing Mui Lancet Reg Health West Pac Articles 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 10.13039/100009945Merck KGaA. Elsevier 2023-09-06 /pmc/articles/PMC10493598/ /pubmed/37701718 http://dx.doi.org/10.1016/j.lanwpc.2023.100898 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Articles Chiang, Chi Leung Lam, Tai Chung Li, James Chun Bong Chan, Kenneth Sik Kwan El Helali, Aya Lee, Yolanda Yim Ping Law, Laalaa Hiu Ting Zheng, Danyang Lo, Anthony Wing Ip Kam, Ngar Woon Li, Wing Sum Cheung, Alice Ka Wai Chow, James Chung Hang Chan, Sunny Po Chung Lai, Jessica Wing Yu Lee, Sarah Wai Man Kong, Feng-Ming (Spring) Ng, Wai Tong Kwong, Dora Lai Wan Lee, Anne Wing Mui Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial |
title | Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial |
title_full | Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial |
title_fullStr | Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial |
title_full_unstemmed | Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial |
title_short | Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial |
title_sort | efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase ii clinical trial |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493598/ https://www.ncbi.nlm.nih.gov/pubmed/37701718 http://dx.doi.org/10.1016/j.lanwpc.2023.100898 |
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