Immunotherapy Drug: More May be Better for Advanced Mesothelioma

The same team of Italian researchers that first reported on the safety and efficacy of the immunotherapy drug tremelimumab for mesothelioma now say that giving more of the drug might be even more effective.

Tremelimumab is a monoclonal antibody that acts on a particular downregulator of the immune system called cytotoxic T-lymphocyte antigen 4 (CTLA4). The goal of tremelimumab is to inhibit the immune system tolerance to tumors, which tends to allow them to grow unchecked. When CTLA4 is reactivated with a drug like tremelimumab, it regains its ability to attack tumors.

Based on the results of their 2013 study that showed a 31% rate of disease control in patients with unresectable mesothelioma who were given tremelimumab, the team tested an intensified dosing schedule in a second group of patients.

Twenty-nine patients with advanced malignant mesothelioma were enrolled in the open-label, single-arm, phase 2 study between July 2012 and July 2013. To be eligible for the study, patients must have failed to respond to previous platinum-based chemotherapy. They also had to have a reasonably good “performance status” or overall health picture. Most of the enrolled patients had the epithelioid variety of mesothelioma and were around 65 years old.

Whereas patients in the first tremelimumab study received 15 mg/kg of the drug every three months, the second group of patients received 10 mg/kg every four weeks for six doses, then every 12 weeks until the disease either progressed or they experienced intolerable side effects.

Although none of the study participants experienced a complete response, meaning that their mesothelioma tumors were eradicated, four of the patients experienced immune-related partial responses. This is twice the percentage of mesothelioma patients who experienced a partial response on the lower dose of tremelimumab.

Equally encouraging was the fact that more than half of the mesothelioma patients achieved disease control, meaning that their tumors stopped growing, for a median of 10.9 months. In the previous study, only 31% of patients experienced disease control and for a median of only 6.2 months. Nearly all of the patients experienced at least one grade 1-2 “adverse event” or complication from the treatment but only two had more serious side effects (half as many as in the lower-lose study).

Writing on their findings in The Lancet, Respiratory Medicine, the research team concludes that the intensified tremelimumab dosing schedule “seems to have clinical and immunological activity in patients with advanced malignant mesothelioma.” The higher dose is currently under investigation in a randomized, double-blind, placebo-controlled, phase 2b study.

Source:

Calabro, L et al, “Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study”, March 25, 2015, The Lancet, Respiratory Medicine, Epub ahead of print.

Calabro, L, et al, “Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial”, September 10, 2013, The Lancet Oncology, Epub ahead of print.