The investigational MAGE-A3 immunotherapeutic did not significantly extend disease-free survival (DFS) in certain patients with postsurgical melanoma when compared with a placebo in a phase III study, thus failing to meet one of its co-primary endpoints, according to an announcement from the vaccine’s manufacturer, GlaxoSmithKline.
However, the company said that based on a unanimous recommendation from the Independent Data Monitoring Committee (IDMC) on the study, the trial will continue until the second co-primary endpoint of DFS in gene signature-positive patients is assessed.
The investigational vaccine, GSK 2132231A, is a special formulation that includes a recombinant fusion protein derived from the melanoma antigen MAGE-3, which is expressed in approximately 65% of cases of stage III melanoma. It is believed that the agent could have immunostimulating and antineoplastic properties and boost antitumor immune responses when given in a vaccine formulation. The phase III DERMA trial was designed to determine whether it was effective in preventing recurrence in patients with melanoma after their tumor had been surgically removed.
The DERMA study enrolled 1349 patients and was conducted across 229 locations. Patients were eligible if they had histologically proven stage IIIB or IIIC cutaneous melanoma presenting with macroscopic lymph node involvement suitable for surgery. Patients’ lymph node tumors had to show expression of the MAGE-A3 gene. Also required was that patients had fully recovered from surgical removal of their tumors and had an ECOG performance status of 0 or 1 when they were randomized to either the GSK 2132231A arm or the placebo arm. Patients received 13 injections administered over the course of 27 months.
In GlaxoSmithKline’s statement, no specific data were provided with regard to the DFS results. The IDMC noted that there were no safety concerns posed by continuing the trial. The results from the additional analysis are expected to become available in 2015, and until that time, the company will remain blinded to all safety and efficacy data.
“We want to thank all patients, their families and healthcare workers for their involvement in the trial and we remain committed to identifying a patient sub-population who may benefit from this investigational treatment,” said Vincent Brichard, Senior Vice-President & Head of Immunotherapeutics for GSK Vaccines, in a statement.
The company is also exploring a MAGE-A3 cancer immunotherapeutic in non-small cell lung cancer. The phase III MAGRIT study is investigating the efficacy of GSK1572932A, another immunotherapeutic containing a melanoma-associated antigen peptide MAGE-A3 epitope, for use in patients with non-small cell lung cancer who express MAGE-A3 following the surgical removal of their primary tumor. That trial enrolled 2278 patients, and the initial data are expected to become available in the first half of 2014.