July 2, 2013

Preliminary results suggest safety, efficacy of tremelimumab as HCC, HCV therapy

Provided by Healio

Sangro B. J Hepatol. 2013;59:81-88.

July 2, 2013

Patients with hepatocellular carcinoma and chronic hepatitis C may experience antiviral and antitumoral benefits from treatment with tremelimumab, according to results of a recent pilot study.

In the phase 2, noncontrolled, multicenter, open-label trial, researchers administered 15 mg/kg tremelimumab intravenously daily to 21 adult patients with chronic HCV genotype 1b and hepatocellular carcinoma (HCC) for 90 days for a maximum of four cycles or until severe toxicity or tumor progression occurred. Toxicity was evaluable in 20 participants and tumor response was measurable in 17 cases.

Forty-six cycles were administered, with 13 patients receiving two or more cycles. Sixteen deaths occurred, with a median overall survival of 8.2 months and survival rates of 64% at 6 months and 43% at 1 year post-treatment.

Partial tumor response occurred in 17.6% of cases, while stable disease resulted in a 76.4% disease control rate. Forty-five percent of patients maintained disease stability for more than 6 months. The median time to tumor progression was 6.48 months.

Median HCV viral loads decreased significantly from baseline (3.78 x 105 IU/mL) to 3.02 x 104 IU/mL at 120 days among 11 participants (P=.011 for difference) and 1.69 x 103 IU/mL at 210 days among six patients (P=.017). Positive viral load was observed in the only patient with evaluable data at 230 days after treatment completion.

No treatment-related deaths occurred. The most common treatment-related adverse events included elevated AST (70%) and ALT levels (55%), skin rash (65%) and fatigue (55%).

“Immune stimulation with monoclonal antibodies that block key targets in the immune synapses, such as [cytotoxic T-lymphocyte-associated antigen 4], may induce objective tumor responses in patients with advanced hepatocellular carcinoma,” Bruno Sangro, MD, PhD, director of the Liver Unit at Clinica Universidad de Navarra in Pamplona, Spain, told Healio.com. “[Also,] that CTLA-4 blockade may exert a potent antiviral effect via immune stimulation warrants further investigation in other chronic infections that lack efficient therapies, including HIV.”

Disclosure: Researcher Ignacio Melero, MD, PhD, has served as a consultant for Pfizer, Bristol-Myers Squibb and AstraZeneca.


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