The pivotal Phase III clinical trial of L-BLP25 (formerly referred to as Stimuvax?) known as START did not meet its primary endpoint of an improvement in overall survival in patients with unresectable, locally advanced stage IIIA or stage IIIB non-small cell lung cancer (NSCLC). The trial was conducted by Merck Serono, a division of Merck KGaA of Darmstadt, Germany, under a license agreement with Oncothyreon.

L-BLP25 is an investigational MUC1 antigen-specific cancer immunotherapy that is designed to stimulate the body’s immune system to identify and target cells expressing the cell surface glycoprotein MUC1. MUC1 is expressed in many cancers, such as non-small cell lung cancer (NSCLC), and has multiple roles in promoting tumor growth and survival. L-BLP25 was being investigated in the Phase III START trial and is currently being investigated in the INSPIRE trial, both for the treatment of unresectable stage III NSCLC.

Merck obtained the exclusive worldwide rights for development and commercialization of L-BLP25 from Oncothyreon Inc., Seattle, Washington, USA, in 2007, in an agreement replacing prior collaboration and supply agreements originally entered in 2001. In Japan, Merck entered into a co-development and co-marketing agreement for L-BLP25 with Ono Pharmaceutical Co., Ltd., Osaka, Japan.

Treatment effects
Despite not meeting the primary endpoint, notable treatment effects were seen for L-BLP25 in certain subgroups. Further analyses are planned in the coming weeks to explore the potential benefit-risk profile of L-BLP25 in certain populations. Merck Serono will discuss these data with external experts and regulatory authorities over the coming months. More detailed results from the START trial will be submitted for publication in a peer reviewed journal and presentation at upcoming scientific meetings.

Scientific insights
“We believe that the START study will offer important scientific insights to the potential for immunotherapies in the treatment of this devastating disease and we intend to discuss these data with scientific community and regulatory authorities to gain their advice on potential next steps,” said Annalisa Jenkins MBBS, MRCP, Head of Global Drug Development and Medical for Merck Serono. The ongoing clinical program of L-BLP25 that includes studies in the Asia Pacific region will continue pending discussion with relevant regulatory agencies.

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Trial design
START was a phase III, randomized, multicenter, double-blind, placebo-controlled trial that assessed the efficacy, safety and tolerability of L-BLP25 in patients with unresectable stage III NSCLC who achieved a response or stable disease after chemoradiotherapy. Patients were randomized to receive either a single low dose of cyclophosphamide followed by L-BLP25 (weekly injections for eight weeks followed by injections every six-weeks until progression) plus best supportive care (BSC) or placebo plus BSC. More than 1,500 patients from 33 countries were recruited into the START trial.

Patient safety in the START trial was monitored frequently by an independent data monitoring committee and no new or unexpected safety concerns were noted for the study. In prior clinical studies, the most frequently reported adverse events included injection site reactions, flu-like symptoms, nausea, cough, fatigue, and dyspnea.

Asian heritage
The INSPIRE study is a Phase III, multi-center, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy, safety and tolerability of L-BLP25 in patients of Asian heritage suffering from unresectable, stage IIIA or IIIB NSCLC who have had a response or stable disease after at least two cycles of platinum-based chemoradiotherapy. The design of the INSPIRE study is almost identical to the START study. INSPIRE will enroll approximately 420 unresectable, stage III NSCLC patients across China, Hong Kong, Korea, Singapore and Taiwan.

Disappointing results
“These results from the START trial are disappointing, both for patients with NSCLC and for the many who have been involved in the L-BLP25 program,” said Robert L. Kirkman, M.D., President and CEO of Oncothyreon. “L-BLP25 has been under development for more than a decade at Oncothyreon and its predecessor company, Biomira Inc. of Edmonton, Alberta, in collaboration with Merck KGaA. The contributions of many employees at each company, committed investigators and, particularly, the many patients who participated in multiple clinical trials over many years are gratefully acknowledged.”

Photo: Annalisa JenkinsMBBS, MRCP, Head of Global Drug Development and Medical for Merck Serono. Photocourtesy Merck Serono

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