PR55259

Merck Serono Announces New Publication of Results of the Phase III START Trial Investigating Tecemotide in Non-Small Cell Lung Cancer in The Lancet Oncology

DARMSTADT, Germany, Dec. 9/PRN=KYODO JBN/ --

    - 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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    Merck is a leading pharmaceutical, chemical and life science company with

total revenues of EUR 11.2 billion in 2012, a history that began in 1668, and a

future shaped by approx. 38,000 employees in 66 countries. Its success is

characterized by innovations from entrepreneurial employees. Merck's operating

activities come under the umbrella of Merck KGaA, in which the Merck family

holds an approximately 70% interest and free shareholders own the remaining

approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and

has been an independent company ever since.

    SOURCE: Merck Serono