Randomized phase II placebo controlled study of codrituzumab in previously treated patients with advanced hepatocellular carcinoma.

Abou-Alfa, Ghassan K; Puig, Oscar; Daniele, Bruno; Kudo, Masatoshi; Merle, Philippe; Park, Joong-Won; Ross, Paul; Peron, Jean-Marie; Ebert, Oliver; Chan, Stephen; Poon, Tung Ping; Colombo, Massimo; Okusaka, Takuji; Ryoo, Baek-Yeol; Minguez, Beatriz; Tanaka, Takayoshi; Ohtomo, Toshihiko; Ukrainskyj, Stacey; Boisserie, Frederic; Rutman, Olga; Chen, Ya-Chi; Xu, Chao; Shochat, Eliezer; Jukofsky, Lori; Reis, Bernhard; Chen, Gong; Di Laurenzio, Laura; Lee, Ray; Yen, Chia-Jui
Journal of hepatology
2016Apr ; 64 ( 14 ) :.
저자 상세정보
Abou-Alfa, Ghassan K -
Puig, Oscar -
Daniele, Bruno -
Kudo, Masatoshi -
Merle, Philippe -
Park, Joong-Won -
Ross, Paul -
Peron, Jean-Marie -
Ebert, Oliver -
Chan, Stephen -
Poon, Tung Ping -
Colombo, Massimo -
Okusaka, Takuji -
Ryoo, Baek-Yeol -
Minguez, Beatriz -
Tanaka, Takayoshi -
Ohtomo, Toshihiko -
Ukrainskyj, Stacey -
Boisserie, Frederic -
Rutman, Olga -
Chen, Ya-Chi -
Xu, Chao -
Shochat, Eliezer -
Jukofsky, Lori -
Reis, Bernhard -
Chen, Gong -
Di Laurenzio, Laura -
Lee, Ray -
Yen, Chia-Jui -
BACKGROUND & AIMS: Codrituzumab, a humanized monoclonal antibody against Glypican-3 (GPC3) that is expressed in hepatocellular carcinoma (HCC), interacts with CD16/Fc款RIIIa and triggers antibody-dependent cytotoxicity. Codrituzumab was studied vs. placebo in a randomized phase II trial in advanced HCC patients who had failed prior systemic therapy.

METHODS: Patients with advanced HCC who had failed prior systemic therapy, ?18years, Eastern cooperative oncology group (ECOG) 0-1, Child-Pugh A were randomized 2:1 to biweekly codrituzumab 1600mg vs. placebo. Patients were stratified based on GPC3 immunohistochemical expression: 2+/3+, 1+, and 0. Primary endpoint was progression free survival. Secondary endpoints include overall survival (OS), tolerability, pharmacokinetics, and an exploratory endpoint in biomarkers analysis.

RESULTS: 185 patients were enrolled: 125 received codrituzumab and 60 placebo: Median age 64/63, 85/75% male, 46/42% Asian, ECOG 0 65/63%, 74/77% having vascular invasion and/or extra-hepatic metastasis. 84%/70% had prior sorafenib. Drug exposure was 98.4% of planned dose, with an identical adverse events profile between the 2 groups. The median progression free survival and overall survival in the codrituzumab vs. placebo groups in months were: 2.6 vs. 1.5 (hazard ratios 0.97, p=0.87), and 8.7 vs. 10 (hazard ratios 0.96, p=0.82). Projected Ctrough at cycle 3day 1 based exposure, high CD16/Fc款RIIIa on peripheral immune cells, and GPC3 expression in the tumor, were all associated with prolonged progression free survival and overall survival.

CONCLUSIONS: Codrituzumab did not show clinical benefit in this previously treated HCC population. Whether higher codrituzumab drug exposure or the use of CD16 and GPC3 as potential biomarkers would improve outcome remain unanswered questions. LAY SUMMARY: Codrituzumab is a manufactured antibody against a liver cancer protein called glypican-3. In this clinical trial, codrituzumab was not found be effective against liver cancer. It was suggested though that a higher dose of codrituzumab or selecting patients with high level of glypican-3 or its mediator CD16 might improve outcome. CLINICAL TRIAL REGISTRATION: This trial is registered at Clinicaltrials.gov (NCT01507168). CI - Copyright ??2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
CD16; Codrituzumab; Glypican-3; Hepatocellular carcinoma

주제명(Target field)
연구참여(Sample size)
질병특성(Condition Category)
연구설계(Study Design)
중재방법(Intervention Type)
중재명칭(Intervention Name)
Codrituzumab was not found be effective against liver cancer.
연구비지원(Fund Source)
근거수준평가(Evidence Hierarchy)
ICD 03