Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: clinical phase I/II trials.
OBJECTIVE
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 Fab'2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials.


METHODS
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).


CONCLUSIONS
Iodine (131I) metuximab injection is safe and active for HCC patients.
Chen
Zhi-Nan
ZN
Cell Engineering Research Centre and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China.
Mi
Li
L
Xu
Jing
J
Song
Fei
F
Zhang
Qing
Q
Zhang
Zheng
Z
Xing
Jin-Liang
JL
Bian
Hui-Jie
HJ
Jiang
Jian-Li
JL
Wang
Xian-Hui
XH
Shang
Peng
P
Qian
Ai-Rong
AR
Zhang
Si-He
SH
Li
Ling
L
Li
Yu
Y
Feng
Qiang
Q
Yu
Xiao-Ling
XL
Feng
Yuan
Y
Yang
Xiang-Min
XM
Tian
Rong
R
Wu
Zhen-Biao
ZB
Leng
Nan
N
Mo
Ting-Shu
TS
Kuang
An-Ren
AR
Tan
Tian-Zhi
TZ
Li
Yun-Chun
YC
Liang
De-Rong
DR
Lu
Wu-Sheng
WS
Miao
Jia
J
Xu
Guo-Hui
GH
Zhang
Zhi-Hui
ZH
Nan
Ke-Jun
KJ
Han
Jun
J
Liu
Qing-Guang
QG
Zhang
Hong-Xin
HX
Zhu
Ping
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051926:Basigin / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004338:Drug Combinations; D007457:Iodine Radioisotopes; C511207:metuximab; D051926:Basigin