Cargando…

A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors

Simultaneous inhibition of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) with bispecific antibodies may improve efficacy over single-agent treatment while limiting toxicity. Cadonilimab is a humanized, bispecific antibody targeting PD-1 and CTLA-4. T...

Descripción completa

Detalles Bibliográficos
Autores principales: Frentzas, Sophia, Gan, Hui K., Cosman, Rasha, Coward, Jermaine, Tran, Ben, Millward, Michael, Zhou, Yiting, Wang, Wenjing, Xia, Dennis, Wang, Zhongmin Maxwell, Li, Baiyong, Xia, Michelle, Desai, Jayesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694581/
https://www.ncbi.nlm.nih.gov/pubmed/37852261
http://dx.doi.org/10.1016/j.xcrm.2023.101242
_version_ 1785153411250913280
author Frentzas, Sophia
Gan, Hui K.
Cosman, Rasha
Coward, Jermaine
Tran, Ben
Millward, Michael
Zhou, Yiting
Wang, Wenjing
Xia, Dennis
Wang, Zhongmin Maxwell
Li, Baiyong
Xia, Michelle
Desai, Jayesh
author_facet Frentzas, Sophia
Gan, Hui K.
Cosman, Rasha
Coward, Jermaine
Tran, Ben
Millward, Michael
Zhou, Yiting
Wang, Wenjing
Xia, Dennis
Wang, Zhongmin Maxwell
Li, Baiyong
Xia, Michelle
Desai, Jayesh
author_sort Frentzas, Sophia
collection PubMed
description Simultaneous inhibition of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) with bispecific antibodies may improve efficacy over single-agent treatment while limiting toxicity. Cadonilimab is a humanized, bispecific antibody targeting PD-1 and CTLA-4. This is a phase 1 study of cadonilimab including dose escalation (n = 39) and dose expansion (n = 80). One dose-limiting toxicity event is observed, with the maximum tolerated dose not reached. 6 mg/kg cadonilimab once every 2 weeks is established as the recommended dose for future studies. The most common treatment-related adverse event is infusion-related reaction (18.5%), mostly grade 1/2 in severity. The incidences of any grade and grade ≥3 immune-related adverse events are 44.5% and 6.7%, respectively. The confirmed overall response rate is 13.4%, and the median duration of response is 12.9 months. Cadonilimab is well tolerated and showed promising efficacy in patients with advanced solid tumors. This study is registered with ClinicalTrials.gov: NCT03261011.
format Online
Article
Text
id pubmed-10694581
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-106945812023-12-05 A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors Frentzas, Sophia Gan, Hui K. Cosman, Rasha Coward, Jermaine Tran, Ben Millward, Michael Zhou, Yiting Wang, Wenjing Xia, Dennis Wang, Zhongmin Maxwell Li, Baiyong Xia, Michelle Desai, Jayesh Cell Rep Med Article Simultaneous inhibition of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) with bispecific antibodies may improve efficacy over single-agent treatment while limiting toxicity. Cadonilimab is a humanized, bispecific antibody targeting PD-1 and CTLA-4. This is a phase 1 study of cadonilimab including dose escalation (n = 39) and dose expansion (n = 80). One dose-limiting toxicity event is observed, with the maximum tolerated dose not reached. 6 mg/kg cadonilimab once every 2 weeks is established as the recommended dose for future studies. The most common treatment-related adverse event is infusion-related reaction (18.5%), mostly grade 1/2 in severity. The incidences of any grade and grade ≥3 immune-related adverse events are 44.5% and 6.7%, respectively. The confirmed overall response rate is 13.4%, and the median duration of response is 12.9 months. Cadonilimab is well tolerated and showed promising efficacy in patients with advanced solid tumors. This study is registered with ClinicalTrials.gov: NCT03261011. Elsevier 2023-10-17 /pmc/articles/PMC10694581/ /pubmed/37852261 http://dx.doi.org/10.1016/j.xcrm.2023.101242 Text en © 2023. 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 Article
Frentzas, Sophia
Gan, Hui K.
Cosman, Rasha
Coward, Jermaine
Tran, Ben
Millward, Michael
Zhou, Yiting
Wang, Wenjing
Xia, Dennis
Wang, Zhongmin Maxwell
Li, Baiyong
Xia, Michelle
Desai, Jayesh
A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors
title A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors
title_full A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors
title_fullStr A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors
title_full_unstemmed A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors
title_short A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors
title_sort phase 1a/1b first-in-human study (compassion-01) evaluating cadonilimab in patients with advanced solid tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694581/
https://www.ncbi.nlm.nih.gov/pubmed/37852261
http://dx.doi.org/10.1016/j.xcrm.2023.101242
work_keys_str_mv AT frentzassophia aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT ganhuik aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT cosmanrasha aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT cowardjermaine aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT tranben aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT millwardmichael aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT zhouyiting aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT wangwenjing aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT xiadennis aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT wangzhongminmaxwell aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT libaiyong aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT xiamichelle aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT desaijayesh aphase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT frentzassophia phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT ganhuik phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT cosmanrasha phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT cowardjermaine phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT tranben phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT millwardmichael phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT zhouyiting phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT wangwenjing phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT xiadennis phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT wangzhongminmaxwell phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT libaiyong phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT xiamichelle phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors
AT desaijayesh phase1a1bfirstinhumanstudycompassion01evaluatingcadonilimabinpatientswithadvancedsolidtumors