A Phase 2b clinical trial of AstraZeneca’s mesothelioma therapy tremelimumab showed no significant difference in survival times between treated and untreated patients.
In addition, five of the treated patients — or 1 percent — died from adverse events, compared with none in the untreated group.
Researchers said they are looking at whether tremelimumab can be effective in a combo therapy.
Results of the international study, which covered 571 patients with peritoneal or pleural malignant mesothelioma, were published in Lancet Oncology. The article was titled “Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial.”
Tremelimumab is an artificially produced antibody that targets toxic T-lymphocyte-associated protein 4, or CTLA-4, which can turn off the body’s defenses against cancer. Inhibiting CTLA-4 increases the chance that the immune system will kill tumor cells.
The U.S. Food and Drug Administration designated tremelimumab an orphan drug in 2015. Orphan diseases affect fewer than 200,000 Americans. The FDA designation is aimed at helping companies obtain faster approvals of the drugs.
AstraZeneca conducted the Phase 2b DETERMINE trial (NCT01843374) at 105 study centers in 19 countries. Participants had pleural or peritoneal malignant mesothelioma that had progressed after one or two treatments and that surgeons were unable to operate on.
The primary objective of the study was for tremelimumab to improve patients’ overall survival. Three hundred eighty-two patients received tremelimumab and 189 patients a placebo between May 2013 and December 2014. Both were administered every four weeks for 28 weeks and then every 12 weeks until treatment was discontinued.
By the end of January 2016, researchers said, 307 or 80 percent of the patients in the tremelimumab group had died, versus 154, or 81 percent, in the placebo group.
“No clinically meaningful differences in progression-free survival or the proportion of patients achieving objective responses [full and partial responses to treatment] were recorded” between the groups, the team wrote.
In addition, the median overall survival rate did not differ greatly between the two groups. It was 7.7 months in the tremelimumab group, versus 7.3 months in the placebo group.
“Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma,” the team said. “The safety profile of tremelimumab was consistent with the known safety profile of CTLA-4 inhibitors. Investigations into whether immunotherapy combination regimens can provide greater efficacy than monotherapies in malignant mesothelioma are ongoing.”
