Randomized Phase II placebo controlled study...
...of codrituzumab in previously treated patients with advanced hepatocellular carcinoma.
LInk to PubMed
PURPOSE:
Codrituzumab, a humanized monoclonal antibody against Glypican-3 (GPC3) that is expressed in HCC, interacts with CD16/ FcγRIIIa and triggers antibody-dependent cytotoxicity. Codrituzumab was studied versus placebo in a randomized phase II trial in advanced HCC patients who had failed prior systemic therapy.
PATIENTS AND METHODS:
Patients with advanced HCC who had failed prior systemic therapy, ⩾18 years, ECOG 0-1, Child-Pugh A were randomized 2:1 to biweekly codrituzumab 1600 mg versus placebo. Patients were stratified based on GPC3 immunohistochemical expression: 2+/3+, 1+, and 0. Primary endpoint was progression free survival (PFS). Secondary endpoints include overall survival (OS), tolerability, pharmacokinetics (PK), 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 PFS and OS in the codrituzumab versus placebo groups in months were: 2.6 versus 1.5 (HR 0.97, P=0.87), and 8.7 versus 10 (HR 0.96, P=0.82). Projected Ctrough at cycle 3 day 1 based exposure, high CD16/FcγRIIIa on peripheral immune cells, and GPC3 expression in the tumor, were all associated with prolonged PFS and OS.
CONCLUSION:
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.