German-based drug company Merck announced on 26 February that the first patient had been enrolled in its global phase III clinical study, START (Stimulating Targeted Antigenic Responses To NSCLC), assessing the efficacy and safety of BLP25 liposome vaccine (Stimuvax®) as a potential treatment for patients with unresectable stage III nonsmall-cell lung cancer (NSCLC).
Enrolment in the study, which will involve more than 1,300 patients in some 30 countries, is now open to patients in the US, where the first randomisation has occurred. Enrolment will later expand to more countries. The company says there are currently no approved maintenance therapies for patients responding to first-line treatment for unresectable stage III NSCLC.
“Patients with advanced lung cancer are in need of new therapies that effectively target cancer cells while providing better safety and tolerability,” said Dr Frances Shepherd, director of medical oncology at Princess Margaret Hospital in Toronto, Canada, and lead investigator of the START study. “Novel therapeutic vaccines such as Stimuvax may help the body’s immune system identify and destroy cancer cells without targeting normal, healthy cells.”
Lung cancer is the leading cause of cancer-related deaths in both men and women worldwide, with about 80% of cases classified as NSCLC. Furthermore, only about 15% of people diagnosed with NSCLC survive the disease after five years. For most patients with NSCLC, current treatments provide limited success.
“The START study is the first phase III programme to evaluate a cancer vaccine in unresectable stage III nonsmall-cell lung cancer, and marks an important milestone for the company in its growing oncology business,” said Dr Wolfgang Wein, senior executive vice-president for oncology at Merck Serono. “Our continued investment in research reflects our confidence in Stimuvax and commitment to developing innovative targeted therapies to advance treatment options for patients with cancer.”
The START study is a randomised, double-blind, placebo-controlled study that will evaluate patients with documented unresectable stage III NSCLC who have had a response or stable disease after at least two cycles of platinum-based chemo-radiotherapy. The study has been designed utilising scientific advice from the European Medicines Agency and has been agreed upon with the US Food and Drug Administration (FDA) through a special protocol assessment. The initiation of the phase III programme data was encouraged by the results of a randomised phase IIb study.
Stimuvax is an innovative cancer vaccine designed to induce an immune response to cancer cells that express MUC1, a protein antigen widely expressed on common cancers. MUC1 is overexpressed on many cancers, including lung, breast and colorectal cancer. Stimuvax is thought to work by stimulating the body’s immune system to identify and destroy cancer cells that express MUC1.
A randomised phase IIb study was conducted in 171 patients with stage IIIb and IV NSCLC with response or stable disease after first-line therapy. While the overall study results were not statistically significant, in the randomisation stratum of patients with stage IIIb locoregional disease, Stimuvax showed a median survival of 30.6 months versus 13.3 months in the control group – an improvement of 17.3 months. In the phase IIb study, side-effects were primarily limited to mild-to-moderate flu-like symptoms, GI disturbances, and mild injection site reactions.