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Codrituzumab noneffective as second line therapy for HCC

Codrituzumab was non-effective in patients who had already failed treatment for hepatocellular carcinoma, according to a phase 2 study published in the Journal of Hepatology.

However, the researchers believe that patient outcome could be improved by using a higher dose of codrituzumab or selecting patients with a greater level of glypican-3 or CD16.

“Single agent codrituzumab at the dose used was well tolerated but could not demonstrate benefit in patients with advanced HCC as a second line therapy in an all-comer population,” Ghassan K. Abou-Alfa, MD, of the Memorial Sloan Kettering Cancer Center and Weil Cornell Medical College in New York, and colleagues wrote. “Based on three independent analyses, increasing codrituzumab exposure, the high [glypican-3] expression and high CD16 expression in circulating immune cells may help predict the efficacy of codrituzumab.”

Codrituzumab — a man-made antibody against the liver cancer protein glypican-3 — works by interacting with CD16/FcγRIIIa and then triggering cytotoxicity. In a randomized placebo-controlled phase 2 study, Abou-Alfa and colleagues studied codrituzumab in adults with advanced HCC who had failed systemic therapy.

The researchers randomly assigned 185 patients to receive either placebo (n = 60; median age, 63 years; 75% men) or biweekly codrituzumab at 1,600 mg (n = 125; median age 64 years; 85% men) and they stratified the patients based on glypican-3 immunohistochemical expression.

The primary endpoint was survival without any progression of disease. Secondary endpoints were overall survival, tolerability, pharmacokinetics and an exploratory endpoint in biomarker analysis.

The researchers found no significant difference in overall survival or progression-free survival between the two groups. However, there was a significant association between survival and a higher dose of codrituzumab as well as greater glypican-3 tumor expression and CD16/FcγRIIIa on peripheral immune cells.

The researchers concluded that codrituzumab did not show any clinical benefit. However, they noted that increasing the dose or selecting patients with higher CD16 and glypican-3 levels might improve patient outcome.

“This would be consistent with the biological hypothesis that codrituzumab would need to have adequate binding to glypican-3 on the tumor cell surface,” the researchers wrote. “This argument will however remain within the theoretical realm, considering that most of its aspects are built on retrospective, unplanned and limited sample size work.” – by Will Offit

Disclosure: Abou-Alfa reports receiving grants and personal fees from Roche. Please see the full study for a list of all other researchers’ relevant financial disclosures.