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OrienX010, an oncolytic virus, in patients with unresectable stage IIIC–IV melanoma: a phase Ib study

BACKGROUND: Melanoma in people of Asian descent presents primarily in non-sun-exposed areas, such as acral and mucosal melanoma. Compared with the predominant sun-exposed area melanomas in Caucasians, acral and mucosal melanomas do not respond as well to immunotherapy and are associated with a worse...

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Autores principales: Cui, ChuanLiang, Wang, Xuan, Lian, Bin, Ji, Qing, Zhou, Li, Chi, Zhihong, Si, Lu, Sheng, Xinan, Kong, Yan, Yu, Jiayi, Li, Siming, Mao, Lili, Tang, Bixia, Dai, Jie, Yan, Xieqiao, Bai, Xue, Andtbacka, Robert, Guo, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8984036/
https://www.ncbi.nlm.nih.gov/pubmed/35383116
http://dx.doi.org/10.1136/jitc-2021-004307
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author Cui, ChuanLiang
Wang, Xuan
Lian, Bin
Ji, Qing
Zhou, Li
Chi, Zhihong
Si, Lu
Sheng, Xinan
Kong, Yan
Yu, Jiayi
Li, Siming
Mao, Lili
Tang, Bixia
Dai, Jie
Yan, Xieqiao
Bai, Xue
Andtbacka, Robert
Guo, Jun
author_facet Cui, ChuanLiang
Wang, Xuan
Lian, Bin
Ji, Qing
Zhou, Li
Chi, Zhihong
Si, Lu
Sheng, Xinan
Kong, Yan
Yu, Jiayi
Li, Siming
Mao, Lili
Tang, Bixia
Dai, Jie
Yan, Xieqiao
Bai, Xue
Andtbacka, Robert
Guo, Jun
author_sort Cui, ChuanLiang
collection PubMed
description BACKGROUND: Melanoma in people of Asian descent presents primarily in non-sun-exposed areas, such as acral and mucosal melanoma. Compared with the predominant sun-exposed area melanomas in Caucasians, acral and mucosal melanomas do not respond as well to immunotherapy and are associated with a worse prognosis. Hence, there is an urgent need for improved treatment for melanoma in Asians. This phase Ib trial evaluated the safety and efficacy of the modified herpes simplex virus-1 oncolytic virus OrienX010 in Chinese patients with unresectable stage IIIC–IV melanoma. METHODS: Patients were treated in two different cohorts. In cohort 08 (n=12), patients received up to 5 mL of 8×10(7) pfu/mL OrienX010 intratumoral injections every 2 weeks until disease progression and responses were evaluated every 6 weeks. In cohort 09 (n=14), patients received up to 10 mL of 8×10(7) pfu/mL OrienX010 intratumoral injections and responses were evaluated every 8 weeks. RESULTS: Between June 2014 and May 2017, 26 patients were enrolled, including 18 (69.2%) patients with acral melanoma. Fever and injection site reaction were the most frequent adverse events. Only one patient experienced a grade ≥3 adverse event and no dose-limiting toxicities were observed. The objective response rate was 19.2% and the disease control rate was 53.8%. The median duration of response was 6.0 months. Antitumor effects were observed in 54.6% of injected lesions and 48.8% of non-injected lesions, including one (16.7%) of six evaluable distant lung metastases. The median progression-free survival was 2.9 months and overall survival was 19.2 months. Compared with patients treated in cohort 08, patients treated in cohort 09 had an improved objective response rate (28.6% vs 8.3%) and a median progression-free survival of 3.0 months vs 2.8 months. CONCLUSIONS: OrienX010 oncolytic virotherapy has a tolerable safety profile with antitumor effects in both injected and non-injected metastases and warrants further evaluation in patients with melanoma. Based on these results, the higher cohort 09 dose (up to 10 mL of 8×10(7) pfu/mL every 2 weeks) was selected as the recommended phase II dose for ongoing trials. TRIAL REGISTRATION NUMBER: CTR20140631 (cohort 08), CTR20150881 (cohort 09).
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spelling pubmed-89840362022-04-22 OrienX010, an oncolytic virus, in patients with unresectable stage IIIC–IV melanoma: a phase Ib study Cui, ChuanLiang Wang, Xuan Lian, Bin Ji, Qing Zhou, Li Chi, Zhihong Si, Lu Sheng, Xinan Kong, Yan Yu, Jiayi Li, Siming Mao, Lili Tang, Bixia Dai, Jie Yan, Xieqiao Bai, Xue Andtbacka, Robert Guo, Jun J Immunother Cancer Oncolytic and Local Immunotherapy BACKGROUND: Melanoma in people of Asian descent presents primarily in non-sun-exposed areas, such as acral and mucosal melanoma. Compared with the predominant sun-exposed area melanomas in Caucasians, acral and mucosal melanomas do not respond as well to immunotherapy and are associated with a worse prognosis. Hence, there is an urgent need for improved treatment for melanoma in Asians. This phase Ib trial evaluated the safety and efficacy of the modified herpes simplex virus-1 oncolytic virus OrienX010 in Chinese patients with unresectable stage IIIC–IV melanoma. METHODS: Patients were treated in two different cohorts. In cohort 08 (n=12), patients received up to 5 mL of 8×10(7) pfu/mL OrienX010 intratumoral injections every 2 weeks until disease progression and responses were evaluated every 6 weeks. In cohort 09 (n=14), patients received up to 10 mL of 8×10(7) pfu/mL OrienX010 intratumoral injections and responses were evaluated every 8 weeks. RESULTS: Between June 2014 and May 2017, 26 patients were enrolled, including 18 (69.2%) patients with acral melanoma. Fever and injection site reaction were the most frequent adverse events. Only one patient experienced a grade ≥3 adverse event and no dose-limiting toxicities were observed. The objective response rate was 19.2% and the disease control rate was 53.8%. The median duration of response was 6.0 months. Antitumor effects were observed in 54.6% of injected lesions and 48.8% of non-injected lesions, including one (16.7%) of six evaluable distant lung metastases. The median progression-free survival was 2.9 months and overall survival was 19.2 months. Compared with patients treated in cohort 08, patients treated in cohort 09 had an improved objective response rate (28.6% vs 8.3%) and a median progression-free survival of 3.0 months vs 2.8 months. CONCLUSIONS: OrienX010 oncolytic virotherapy has a tolerable safety profile with antitumor effects in both injected and non-injected metastases and warrants further evaluation in patients with melanoma. Based on these results, the higher cohort 09 dose (up to 10 mL of 8×10(7) pfu/mL every 2 weeks) was selected as the recommended phase II dose for ongoing trials. TRIAL REGISTRATION NUMBER: CTR20140631 (cohort 08), CTR20150881 (cohort 09). BMJ Publishing Group 2022-04-05 /pmc/articles/PMC8984036/ /pubmed/35383116 http://dx.doi.org/10.1136/jitc-2021-004307 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Oncolytic and Local Immunotherapy
Cui, ChuanLiang
Wang, Xuan
Lian, Bin
Ji, Qing
Zhou, Li
Chi, Zhihong
Si, Lu
Sheng, Xinan
Kong, Yan
Yu, Jiayi
Li, Siming
Mao, Lili
Tang, Bixia
Dai, Jie
Yan, Xieqiao
Bai, Xue
Andtbacka, Robert
Guo, Jun
OrienX010, an oncolytic virus, in patients with unresectable stage IIIC–IV melanoma: a phase Ib study
title OrienX010, an oncolytic virus, in patients with unresectable stage IIIC–IV melanoma: a phase Ib study
title_full OrienX010, an oncolytic virus, in patients with unresectable stage IIIC–IV melanoma: a phase Ib study
title_fullStr OrienX010, an oncolytic virus, in patients with unresectable stage IIIC–IV melanoma: a phase Ib study
title_full_unstemmed OrienX010, an oncolytic virus, in patients with unresectable stage IIIC–IV melanoma: a phase Ib study
title_short OrienX010, an oncolytic virus, in patients with unresectable stage IIIC–IV melanoma: a phase Ib study
title_sort orienx010, an oncolytic virus, in patients with unresectable stage iiic–iv melanoma: a phase ib study
topic Oncolytic and Local Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8984036/
https://www.ncbi.nlm.nih.gov/pubmed/35383116
http://dx.doi.org/10.1136/jitc-2021-004307
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