Date: 2014-09-12
Type of information: Halting of the trial
phase: 3
Announcement: discontinuation of development
Company: Merck Serono, a Merck KGaA company (Germany)
Product: L-BLP25 - Stimuvax® (tecemotide)
Action
mechanism: 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 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.
Disease: unresectable, locally advanced stage IIIA or IIIB non-small cell lung cancer (NSCLC)
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The START (Stimulating Targeted Antigenic Responses To NSCLC) study was 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 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 study involves more than 1,500 patients in 33 countries. The primary endpoint of the START study is overall survival (OS). (NCT00409188)
Latest
news: * On September 12, 2014, Merck KGaA announced that its biopharmaceutical division Merck Serono will discontinue the clinical development program of its investigational MUC1 antigen-specific cancer immunotherapy tecemotide (also known as L-BLP25) as a monotherapy in Stage III non-small cell lung cancer (NSCLC).
The company’s decision to discontinue the current clinical program in NSCLC, which includes the Phase III START2 and INSPIRE studies, follows recent results from a planned analysis of EMR 63325-009, a randomized, double-blind, placebo-controlled Phase I/II study in Japanese patients with Stage III unresectable, locally advanced NSCLC who had received concurrent or sequential chemoradiotherapy (CRT), with a minimum of two cycles of platinum-based chemotherapy and radiation dose ≥50 Gy. Of
the patients included in the Phase II part of the study, the majority had received concurrent CRT. The results indicate that no effect has been observed for either the primary endpoint, overall survival (OS), or for any of the secondary endpoints (progression-free survival [PFS], time to progression [TTP] and time to treatment failure). An analysis of the reported adverse events has not identified a clinically meaningful difference in the frequency between treatment groups. Although the trial was not powered to demonstrate a statistically significant difference in benefit between the two arms, Merck Serono made the recommendation to stop the investigational treatment for patients in the EMR 63325-009 study in Japan. Merck Serono has made the decision to discontinue all other Merck Serono-sponsored clinical trials with tecemotide in NSCLC worldwide. Those patients on active treatment with tecemotide can undergo an individual assessment by their treating physician and apply to receive further treatment outside of the studies. The company will continue to supply tecemotide for ongoing investigator-sponsored trials in other indications in accordance with Merck’s agreements with the sponsors of these studies.* On May 16, 2013, Merck KGaA has announced detailed results from the randomized Phase III START* trial of its investigational MUC1 antigen-specific cancer immunotherapy L-BLP25 (formerly referred to as Stimuvax®) in patients with unresectable, locally advanced Stage III non-small cell lung cancer (NSCLC). These results will be presented at the American Society of Clinical Oncology (ASCO) 2013 Annual Meeting in Chicago. The primary endpoint of improving overall survival (OS) was not met. In a predefined subgroup of patients receiving initial concurrent chemoradiotherapy (CRT), a combination of chemotherapy and radiotherapy given at the same time, a median overall survival of 30.8 months versus 20.6 months was observed based on a post hoc analysis in patients treated with L-BLP25 versus placebo respectively (HR 0.78, 95% CI 0.64–0.95, p=0.016, n=806). The results of the START trial will be presented during the Oral Abstract Session “Lung Cancer – Non-Small Cell Local-Regional /Small Cell / Other Thoracic Cancers” from 09.45 am to 12.45 pm on Tuesday,June 4.
* On December 19, 2012, MerckKGaA has announced that the Phase III STARTa trial of its investigational product L-BLP25 (formerly referred to as Stimuvax®) in patients with unresectable, locally advanced stage IIIA or IIIB non-small cell lung cancer (NSCLC) did not meet its primary endpoint to demonstrate a statistically significant improvement in overall survival (OS). Despite not meeting the primary endpoint, notable treatment effects were seen for L-BLP25 in certain subgroups.
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.
Further analyses are planned in the coming weeks to explore the potential benefit-risk profile of L-BLP25 in certain populations. This data will be discussed with external experts and regulatory authorities over the coming months. The START study results will be submitted for publication in a peer-reviewed journal and presented at a future international scientific meeting.
The ongoing clinical program of L-BLP25 that includes studies in the Asia Pacific region will continue pending discussion with relevant regulatory agencies. 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.
