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mapatumumab · 2 trials · 2 indications
Time to progression is defined as the time from randomization to radiologic disease progression based on blinded independent review (BICR) of imaging scans using modified Response Evaluation Criteria in Solid Tumors assessment (mRECIST) for hepatocellular carcinoma. The primary analysis was performed using Kaplan Meier methods. The median time to progression is reported with one-sided 90% confidence interval. Analysis was performed on the modified Intent to Treat (mITT) Population which comprised of all randomized participants who received at least part of 1 dose of study agent (mapatumumab/placebo and/or sorafenib) with participants analyzed according to the groups to which they were randomized. NA indicates upper limit was not measurable as one-sided confidence interval is presented.
| Arm | Type | Description |
|---|---|---|
| Sorafenib plus mapatumumab | EXPERIMENTAL | Mapatumumab 30 milligrams (mg)/kilogram (kg) intravenously on Day 1 of each cycle (i.e. every 21 days) plus sorafenib 400 mg orally twice daily continuously in each cycle until radiologic disease progression or unacceptable toxicity |
| Sorafenib plus Placebo | PLACEBO_COMPARATOR | Placebo intravenously on Day 1 of each cycle (i.e. every 21 days) plus sorafenib 400 mg orally twice daily continuously in each cycle until radiologic disease progression or unacceptable toxicity |
| A | EXPERIMENTAL | mapatumumab and sorafenib |
| Name | Type | Description |
|---|---|---|
| Mapatumumab | DRUG | Mapatumumab will be supplied as a lyophilized formulation in 10 mL vials containing 100 mg mapatumumab for intravenous infusion at the dose of 30 mg/kg. |
| Placebo | DRUG | Normal saline solution for intravenous infusion will be administered as placebo for mapatumumab |
| Sorafenib | DRUG | Sorafenib will be supplied as tablets, each containing 274 mg sorafenib tosylate, equivalent to 200 mg of sorafenib, to be administered 400 mg (2 x 200 mg tablets) orally twice daily. |
Inclusion Criteria: * Child-Pugh Class A. * Barcelona Clinic Liver Cancer (BCLC) advanced stage (C) hepatocellular carcinoma, or BCLC intermediate stage (B) hepatocellular carcinoma if treatment with transarterial chemoembolization is not considered appropriate * Measurable disease demonstrating in...
Mapatumumab was studied for the treatment of advanced hepatocellular carcinoma, a form of liver cancer. Both of its clinical trials evaluated the drug in combination with sorafenib in adults with advanced disease. It is an investigational agent and has not been approved for any indication.
Mapatumumab targets TNFRSF10A, also known as death receptor 4 or TRAIL receptor 1. It is an agonist monoclonal antibody, meaning it binds this receptor to activate signaling rather than block it. Agonist activity at TNFRSF10A is intended to trigger cell death pathways in tumor cells.
Mapatumumab was developed by GSK plc, which trades under the ticker GSK. The company sponsored both Phase 1 trials of the antibody in advanced hepatocellular carcinoma. Both studies have been completed.
Mapatumumab is in Phase 1 development and is investigational. It has not been approved by the FDA or any other regulatory agency for hepatocellular carcinoma or any other indication. Its two recorded trials were both Phase 1 studies, and neither is currently active.
Mapatumumab has been studied in two completed Phase 1 trials. NCT01258608 tested it with sorafenib in advanced hepatocellular carcinoma across the United States, Germany, Poland, Puerto Rico, Romania, Russia, and Ukraine, enrolling 101 participants. NCT00712855 tested the same combination in the United States, enrolling 23 participants.
The two completed Phase 1 trials of mapatumumab enrolled a combined total of 124 participants. NCT01258608 enrolled 101 patients and NCT00712855 enrolled 23 patients. Both studies were randomized, double blind, and placebo controlled, and both required participants to be at least 18 years old.