Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: Clinical Phase I/II trials

Zhi Nan Chen; Li Mi; Jing Xu; Fei Song; Qing Zhang; Zheng Zhang; Jin Liang Xing; Hui Jie Bian; Jian Li Jiang; Xian Hui Wang; Peng Shang; Ai Rong Qian; Si He Zhang; Ling Li; Yu Li; Qiang Feng; Xiao Ling Yu; Yuan Feng; Xiang Min Yang; Rong Tian; Zhen Biao Wu; Nan Leng; Ting Shu Mo; An Ren Kuang; Tian Zhi Tan; Yun Chun Li; De Rong Liang; Wu Sheng Lu; Jia Miao; Guo Hui Xu; Zhi Hui Zhang; Ke Jun Nan; Jun Han; Qing Guang Liu; Hong Xin Zhang; Ping Zhu

doi:10.1016/j.ijrobp.2005.12.034

Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (¹³¹I) metuximab injection: Clinical Phase I/II trials

Zhi Nan Chen, Li Mi, Jing Xu, Fei Song, Qing Zhang, Zheng Zhang, Jin Liang Xing, Hui Jie Bian, Jian Li Jiang, Xian Hui Wang, Peng Shang, Ai Rong Qian, Si He Zhang, Ling Li, Yu Li, Qiang Feng, Xiao Ling Yu, Yuan Feng, Xiang Min Yang, Rong TianZhen Biao Wu, Nan Leng, Ting Shu Mo, An Ren Kuang, Tian Zhi Tan, Yun Chun Li, De Rong Liang, Wu Sheng Lu, Jia Miao, Guo Hui Xu, Zhi Hui Zhang, Ke Jun Nan, Jun Han, Qing Guang Liu, Hong Xin Zhang, Ping Zhu

Research output: Contribution to journal › Article › peer-review

151 Scopus citations

Abstract

Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine (¹³¹I) metuximab injection (Licartin), a novel ¹³¹I-labeled HAb18G/CD147-specific monoclonal antibody F(ab')₂ fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p < 0.0001 or p = 0.0019). Conclusion: Iodine (¹³¹I) metuximab injection is safe and active for HCC patients.

Original language	English
Pages (from-to)	435-444
Number of pages	10
Journal	International Journal of Radiation Oncology Biology Physics
Volume	65
Issue number	2
DOIs	https://doi.org/10.1016/j.ijrobp.2005.12.034
State	Published - 1 Jun 2006
Externally published	Yes

Keywords

Clinical trial
HAb18G/CD147
Hepatocellular carcinoma
Monoclonal antibody
Radioimmunotherapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ijrobp.2005.12.034

Cite this

Chen, Z. N., Mi, L., Xu, J., Song, F., Zhang, Q., Zhang, Z., Xing, J. L., Bian, H. J., Jiang, J. L., Wang, X. H., Shang, P., Qian, A. R., Zhang, S. H., Li, L., Li, Y., Feng, Q., Yu, X. L., Feng, Y., Yang, X. M., ... Zhu, P. (2006). Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (¹³¹I) metuximab injection: Clinical Phase I/II trials. International Journal of Radiation Oncology Biology Physics, 65(2), 435-444. https://doi.org/10.1016/j.ijrobp.2005.12.034

@article{e94560a305f647fcb864db3a26e1d072,

title = "Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: Clinical Phase I/II trials",

abstract = "Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine (131I) metuximab injection (Licartin), a novel 131I-labeled HAb18G/CD147-specific monoclonal antibody F(ab')2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p < 0.0001 or p = 0.0019). Conclusion: Iodine (131I) metuximab injection is safe and active for HCC patients.",

keywords = "Clinical trial, HAb18G/CD147, Hepatocellular carcinoma, Monoclonal antibody, Radioimmunotherapy",

author = "Chen, {Zhi Nan} and Li Mi and Jing Xu and Fei Song and Qing Zhang and Zheng Zhang and Xing, {Jin Liang} and Bian, {Hui Jie} and Jiang, {Jian Li} and Wang, {Xian Hui} and Peng Shang and Qian, {Ai Rong} and Zhang, {Si He} and Ling Li and Yu Li and Qiang Feng and Yu, {Xiao Ling} and Yuan Feng and Yang, {Xiang Min} and Rong Tian and Wu, {Zhen Biao} and Nan Leng and Mo, {Ting Shu} and Kuang, {An Ren} and Tan, {Tian Zhi} and Li, {Yun Chun} and Liang, {De Rong} and Lu, {Wu Sheng} and Jia Miao and Xu, {Guo Hui} and Zhang, {Zhi Hui} and Nan, {Ke Jun} and Jun Han and Liu, {Qing Guang} and Zhang, {Hong Xin} and Ping Zhu",

year = "2006",

month = jun,

day = "1",

doi = "10.1016/j.ijrobp.2005.12.034",

language = "英语",

volume = "65",

pages = "435--444",

journal = "International Journal of Radiation Oncology Biology Physics",

issn = "0360-3016",

publisher = "Elsevier Inc.",

number = "2",

}

Chen, ZN, Mi, L, Xu, J, Song, F, Zhang, Q, Zhang, Z, Xing, JL, Bian, HJ, Jiang, JL, Wang, XH, Shang, P , Qian, AR, Zhang, SH, Li, L, Li, Y, Feng, Q, Yu, XL, Feng, Y, Yang, XM, Tian, R, Wu, ZB, Leng, N, Mo, TS, Kuang, AR, Tan, TZ, Li, YC, Liang, DR, Lu, WS, Miao, J, Xu, GH, Zhang, ZH, Nan, KJ, Han, J, Liu, QG, Zhang, HX & Zhu, P 2006, 'Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (¹³¹I) metuximab injection: Clinical Phase I/II trials', International Journal of Radiation Oncology Biology Physics, vol. 65, no. 2, pp. 435-444. https://doi.org/10.1016/j.ijrobp.2005.12.034

TY - JOUR

T1 - Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection

T2 - Clinical Phase I/II trials

AU - Chen, Zhi Nan

AU - Mi, Li

AU - Xu, Jing

AU - Song, Fei

AU - Zhang, Qing

AU - Zhang, Zheng

AU - Xing, Jin Liang

AU - Bian, Hui Jie

AU - Jiang, Jian Li

AU - Wang, Xian Hui

AU - Shang, Peng

AU - Qian, Ai Rong

AU - Zhang, Si He

AU - Li, Ling

AU - Li, Yu

AU - Feng, Qiang

AU - Yu, Xiao Ling

AU - Feng, Yuan

AU - Yang, Xiang Min

AU - Tian, Rong

AU - Wu, Zhen Biao

AU - Leng, Nan

AU - Mo, Ting Shu

AU - Kuang, An Ren

AU - Tan, Tian Zhi

AU - Li, Yun Chun

AU - Liang, De Rong

AU - Lu, Wu Sheng

AU - Miao, Jia

AU - Xu, Guo Hui

AU - Zhang, Zhi Hui

AU - Nan, Ke Jun

AU - Han, Jun

AU - Liu, Qing Guang

AU - Zhang, Hong Xin

AU - Zhu, Ping

PY - 2006/6/1

Y1 - 2006/6/1

N2 - Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine (131I) metuximab injection (Licartin), a novel 131I-labeled HAb18G/CD147-specific monoclonal antibody F(ab')2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p < 0.0001 or p = 0.0019). Conclusion: Iodine (131I) metuximab injection is safe and active for HCC patients.

AB - Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine (131I) metuximab injection (Licartin), a novel 131I-labeled HAb18G/CD147-specific monoclonal antibody F(ab')2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p < 0.0001 or p = 0.0019). Conclusion: Iodine (131I) metuximab injection is safe and active for HCC patients.

KW - Clinical trial

KW - HAb18G/CD147

KW - Hepatocellular carcinoma

KW - Monoclonal antibody

KW - Radioimmunotherapy

UR - http://www.scopus.com/inward/record.url?scp=33646251826&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2005.12.034

DO - 10.1016/j.ijrobp.2005.12.034

M3 - 文章

C2 - 16690431

AN - SCOPUS:33646251826

SN - 0360-3016

VL - 65

SP - 435

EP - 444

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

IS - 2

ER -