MRK Merck KGAA

DARMSTADT, Germany, December 9, 2013 /PRNewswire/ --

• Publication offers detailed results of START, including an exploratory analysis of the clinically meaningful survival prolongation with tecemotide maintenance therapy in a predefined subgroup of patients treated with concurrent chemoradiotherapy
• As previously announced Merck Serono will continue the development of tecemotide in non-small cell lung cancer based on the results of this subgroup analysis

Merck Serono, the biopharmaceutical division of Merck, today announced that The Lancet Oncology has published results from the Phase III trial of its investigational MUC1 antigen specific cancer immunotherapy tecemotide (also known as L-BLP25) in patients with unresectable, locally advanced Stage III non-small cell lung cancer (NSCLC), known as the START* trial.

Data included in the publication^[1], and first presented at the American Society of Clinical Oncology (ASCO) 2013^[2], showed that the primary endpoint of overall survival (OS) was not met. Median OS was 25.6 months for patients in the tecemotide group compared with 22.3 months for those in the placebo group (adjusted HR: 0.88, 95% CI 0.75-1.03, p=0.123). The publication includes an exploratory analysis of a predefined subgroup of patients in the START trial who received tecemotide after concurrent chemoradiotherapy (CRT).^[1] Concurrent CRT is a combination of chemotherapy and radiotherapy given at the same time. Patients in this subgroup achieved a median OS of 30.8 months vs. 20.6 months in patients treated with placebo (n=806; HR: 0.78; 95% CI 0.64-0.95; p=0.016).^[1] In patients receiving sequential CRT followed by tecemotide or placebo a median OS of 19.4 months was observed for the tecemotide group compared with 24.6 months for the placebo group (n=433; HR 1.12; 95% CI 0.87-1.44; p=0.38).

"These results have generated considerable interest within the scientific community and we hope that the publication will provide additional context to help inform future immuno-oncology research," said Dr. Charles Butts, Cross Cancer Institute, University of Alberta, Edmonton, Canada, clinical investigator of the START trial and member of the corresponding steering committee. "In the article we have hypothesized potential reasons why the combination with concurrent CRT demonstrated increased overall survival in START compared to combination with sequential CRT and we look forward to investigating tecemotide further to determine if it is a suitable therapeutic option that could help deliver positive outcomes for patients."

As previously announced, Merck Serono will continue the development of tecemotide under a new Phase III trial called START2, based on the results of the START trial. The START2 trial is a multicenter, randomized, double-blind, placebo-controlled trial designed to assess the efficacy, safety and tolerability of tecemotide in patients suffering from unresectable, locally advanced (Stage IIIA or IIIB) NSCLC who have had a response or stable disease after at least two cycles of platinum-based concurrent CRT. Concurrent CRT is the standard of care for these patients. The trial's primary endpoint is OS. Merck has received Scientific Advice from the European Medicines Agency (EMA) on the program, and has reached an agreement with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for the Phase III international randomized trial.

Dr. Annalisa Jenkins, Head of Global Head of Global Research and Development for Merck Serono, said: "The publication of the START trial confirms the interest of the scientific medical community in the potential that immunotherapy may offer for patients living with lung cancer. We continue to pursue development of tecemotide in the hope that it can potentially bring meaningful benefit for patients fighting this devastating disease."

Tecemotide is an investigational MUC1 antigen-specific cancer immunotherapy designed to stimulate the body's immune system to identify and target cancer cells expressing the cell-surface glycoprotein MUC1.^[3],[4] MUC1 is expressed in many cancers, including NSCLC, and has multiple roles in tumor growth and survival.^[3],[5]

Globally, lung cancer is the most common cause of cancer-related deaths in men and the second most common in women, responsible for almost twice as many deaths as both breast and prostate cancer combined.^[6] NSCLC is the most common type of lung cancer, accounting for 80-85% of all lung cancers, and locally advanced or Stage III disease accounts for approximately 30% of patients with NSCLC.^[7],[8] Unfortunately, at diagnosis, most patients have advanced or metastatic disease with a very poor prognosis.^[9] There is an especially urgent and ongoing need for new approaches for patients with advanced, unresectable NSCLC.

^[*] START: Stimulating Targeted Antigenic Responses To NSCLC

References

1. Butts C, et al. The Lancet Oncology 2013. Available at: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70510-2/fulltext. Last accessed on December 9, 2013.
2. Shepherd F, et al. Poster discussion session at the European Cancer Congress 2013, September 29. Abstract No:3419.
3. Agrawal B, et al. Int Immunol 1998;10(12):1907-16.
4. Palmer M, et al. Clin Lung Cancer 2001;3(1):49-57.
5. Sangha R and Butts C. Clin Cancer Res 2007;13:(15 pt 2)4652s-4654s.
6. Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. Available at: http://globocan.iarc.fr. Last accessed on March 11, 2013.
7. D'Addario G, et al. Ann Oncol 2008;19 (suppl 2):ii39-40.
8. Crino L, et al. Ann Oncol 2010;21(suppl 5):v103-v115.
9. Bunn PA, et al. Oncologist 2008;13(suppl 1):1-4.

About tecemotide

Tecemotide 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, including non-small cell lung cancer (NSCLC), and has multiple roles in tumor growth and survival. Tecemotide is currently being investigated in the Phase III START and INSPIRE trials for the treatment of unresectable, locally advanced Stage III NSCLC.

Merck obtained the exclusive worldwide rights for development and commercialization of tecemotide from Oncothyreon Inc., Seattle, Washington, U.S., 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 tecemotide with Ono Pharmaceutical Co., Ltd., Osaka, Japan.

The START2 trial is a Phase III, multicenter, randomized, double-blind, placebo-controlled clinical trial designed to assess the efficacy, safety and tolerability of tecemotide in patients suffering from unresectable, locally advanced (Stage IIIA or IIIB) NSCLC who have had a response or stable disease after at least two cycles of platinum-based concurrent chemoradiotherapy (CRT). The primary endpoint of START2 trial is overall survival.

The initial Phase III trial START is a multicenter, randomized, double-blind, placebo-controlled clinical trial designed to assess the efficacy, safety and tolerability of tecemotide in patients suffering from unresectable, locally advanced (Stage IIIA or IIIB) NSCLC who have had a response or stable disease after at least two cycles of platinum-based chemoradiotherapy (concurrent or sequential). The trial involves 1,239 patients in 33 countries. The primary endpoint of overall survival was not met in the START trial.

INSPIRE (tecemotide liposome vaccine trial In Asian NSCLC Patients: Stimulating Immune REsponse) is a Phase III, multicenter, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy, safety and tolerability of tecemotide in patients suffering from unresectable, locally advanced Stage IIIA or IIIB NSCLC who have had a response or stable disease after at least two cycles of platinum-based concurrent chemoradiotherapy. The design of INSPIRE is almost identical to the START trial, however, due to the results of START, only subjects who have received concurrent CRT are being entered into INSPIRE. INSPIRE is enrolling approximately 420 unresectable, locally advanced Stage III NSCLC patients across China, Hong Kong, Korea, Singapore and Taiwan.

Tecemotide is currently under clinical investigation and has not been approved for use in the U.S., Europe, Canada, or elsewhere. Tecemotide has not been proven to be either safe or effective and any claims of safety and effectiveness can be made only after regulatory review of the data and approval of the labeled claims.

About Merck Serono

Merck Serono is the biopharmaceutical division of Merck. With headquarters in Darmstadt, Germany, Merck Serono offers leading brands in 150 countries to help patients with cancer, multiple sclerosis, infertility, endocrine and metabolic disorders as well as cardiovascular diseases. In the United States and Canada, EMD Serono operates as a separately incorporated subsidiary of Merck Serono.

Merck Serono discovers, develops, manufactures and markets prescription medicines of both chemical and biological origin in specialist indications. We have an enduring commitment to deliver novel therapies in our core focus areas of neurology, oncology, immuno-oncology and immunology.

For more information, please visit http://www.merckserono.com.

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