Tecemotide (INN; emepepimut-S (USAN); formerly known as BLP25 or EMD 531444) is a synthetic lipopeptide that is used as antigen in an investigational therapeutic cancer vaccine (formerly known as Stimuvax, L-BLP25, BLP25 liposomal vaccine, or BLP25 liposome vaccine). The investigational therapeutic cancer vaccine is designed to induce a cellular immune response to cancer cells that express MUC1, a glycoprotein antigen that is widely over-expressed on common cancers such as lung cancer, breast cancer, prostate cancer, and colorectal cancer. The cellular immune response may lead to a rejection of tumor tissue expressing the MUC1 antigen.
Collaboration
Tecemotide was developed – until Clinical trial phase II – by the Canadian biotech company Biomira Inc., which changed its company name to Oncothyreon Inc. in 2007.Biomira announces plan to change name to Oncothyreon Oncothyreon is now located in Seattle, Washington, and it changed its name to SGEN after a merger and acquisition in March 2018.
In 2001, Merck KGaA, of Darmstadt, Germany, entered into a collaboration and supply agreement with Biomira. In 2007, Merck KGaA acquired the exclusive worldwide marketing rights from Biomira, and Merck KGaA has since then been entirely responsible for the further clinical development of tecemotide.Aug 8, 2007, Biomira and Merck KGaA sign amended and restated collaboration and supply agreements related to Stimuvax In 2008, Merck KGaA acquired the manufacturing rights for tecemotide from Oncothyreon.Dec 18, 2008, Merck KGaA acquires manufacturing rights for Stimuvax from Oncothyreon In 2011, Ono Pharmaceutical Company, of Japan, acquired a co-development and co-marketing license for tecemotide in Japan; Ono paid Merck KGaA 5 million euros.Merck KGaA press release from October 4, 2011
Composition
Tecemotide is a synthetic lipopeptide that is 27 amino acids long. Its molecular formula is , and its amino acid sequence is S T A PPAH G VTSAPDTRPAPGSTAPPKG. The first 25 amino acids of tecemotide are derived from the mucin 1 (MUC1, carcinoma-associated mucin, episialin, or CD227) sequence. The 26th modified amino acid, K, is palmityl-lysine (N6-(1-oxohexadecyl)-L-lysine), and the 27th is glycine.WHO Drug Information, Vol. 26, No. 4, 2012; Proposed INN: List 108
Structure of the cancer vaccine
In the investigational therapeutic cancer vaccine (formerly known as Stimuvax, L-BLP25, BLP25 liposomal vaccine or BLP25 liposome vaccine), the antigen tecemotide is anchored — together with the adjuvant 3-O-deacyl-4′-monophosphoryl lipid A (MPL) — in the membrane of the liposome made from the lipids cholesterol, dimyristoyl phosphatidylglycerol (DMPG), and dipalmitoyl phosphatidylcholine. MPL is a derivative of the lipid A molecule found in the membrane of Gram-negative bacteria used as an adjuvant to initiate a non-specific immune stimulus, thereby stimulating the activation of antigen-presenting cells (APCs) through the toll-like receptor 4 (TLR-4) as well as macrophages. MPL is also used as an adjuvant in other vaccines, like Cervarix, a vaccine against certain types of cancer-causing human papillomavirus (HPV).
The precise mixture of lipids in the vaccine, as well as providing the structure of the liposome, is also formulated to enhance the uptake of the vaccine by the aforementioned antigen-presenting cells.
The cancer vaccine is a lyophilized powder, which is formulated to contain 300 μg of tecemotide and 150 μg of MPL per vial.
Clinical trials
Overview and results of all trials
Tecemotide clinical trials (as of September 2, 2014)ClinicalTrials.gov sorted by (estimated) primary completion date:The primary completion date is defined as the date when the final subject was examined or received an intervention for the purposes of final collection of data for the primary outcome.
Clinical trials: Lung cancer, Breast cancer, Prostate cancer, Colorectal cancer, and Multiple myeloma NCT Number /Title Other IDs Start date (Estimated) Primary Completion Date Recruitment Conditions Interventions Phases Enrollment (Patients) Sponsor / Collaborators B25-LG-304 / EMR 63325-005 August 2000 March 2006 Lung Neoplasms, Carcinoma, Non-Small-Cell Lung Biological: BLP25 Liposome Vaccine plus best supportive care; Other: Best Supportive Care (BSC) Phase 2 171 Merck KGaA A Phase IIb clinical trial of 171 patients with inoperable stage IIIb non-small-cell lung cancer (NSCLC), in which tecemotide showed a trend towards extending median overall survival from 13.3 months for patients receiving best supportive care (BSC) to 30.6 months for patients receiving tecemotide plus BSC. Although this represents a subgroup analysis that is not statistically significant (with a nonsignificant P-value: p = 0.16), the magnitude of the difference and its durability over a prolonged period of follow up suggest an efficacy signal for the vaccine and would support further testing of tecemotide in a definitive phase III trial. Reported side effects included mild-to-moderate flu-like symptoms, gastrointestinal disturbances, and mild injection-site reactions. NCT00157196 Safety Study of BLP25 Liposome Vaccine in Non-Small Cell Lung Cancer Patients With Unresectable Stage III Disease B25-LG-305 / EMR 63325-006 April 2005 September 2009 Carcinoma, Non-Small-Cell Lung, Lung Neoplasms Biological: BLP25 Liposome Vaccine Phase 2 22 Merck KGaA NCT00925548 STRIDE - STimulating Immune Response In aDvanced brEast Cancer , EMR 200038–010, 2008-005544-17 September 2009 August 2010 Breast Cancer Biological: Tecemotide (L-BLP25) and Hormonal Treatment, Biological: Placebo of tecemotide (L-BLP25) and Hormonal Treatment, Drug: cyclophosphamide, Drug: sodium chloride (NaCl) Phase 3 16 EMD Serono A thirty-site phase III trial (STRIDE) began in September 2009 on 900 women. The purpose of this study is to determine whether the addition of tecemotide to hormonal treatment is effective in prolonging progression-free survival in postmenopausal women with endocrine-sensitive inoperable locally advanced, recurrent, or metastatic breast cancer.UPDATE 2-Merck to test Stimuvax cancer drug in Phase III (Thomson Reuters) The U.S. Food and Drug Administration (FDA) put the Phase III STRIDE trial on hold in March 2010 after a patient participating in a Phase II clinical trial with tecemotide in patients with multiple myeloma developed encephalitis.Merck KGaA press release from June 17, 2010 The study was terminated in August 2010 (16 patients were enrolled in the study). NCT01094548 Study of Stimuvax in Patients With Slowly Progressive Multiple Myeloma With no Symptoms and Who Have Had no Chemotherapy EMR63325-008 February 2008 February 2011 Multiple Myeloma Biological: L-BLP25, cyclophosphamide prior to first vaccination, Biological: L-BLP25 Phase 2 34 Merck KGaA NCT00409188 Cancer Vaccine Study for Unresectable Stage III Non-small Cell Lung Cancer , EMR 63325-001 January 2007 August 2012 Non-small Cell Lung Cancer Biological: Tecemotide (L-BLP25), Biological: Placebo Phase 3 1513 EMD Serono, Merck KGaA The primary endpoint of overall survival was not met in the START trial.Experimental Cancer Treatment L-BLP25 (Stimuvax) Did Not Meet Primary Endpoint of Improvement in Overall Survival in Pivotal Phase III Trial in Patients with Non-Small Cell Lung Cancer (Onco'Zine - The International Cancer Network) However, the exploratory subgroup analysis in the START trial generated a reasonable hypothesis to warrant additional study. NCT01731587 Anti-cancDer MUC1-specific Immunotherapy for Unresectable Stage III Non-small Cell Lung Cancer , EMR 63325–019, 2012-001435-31 Non-small Cell Lung Cancer (NSCLC) Stage III Other: Biological: MUC1 peptide specific immunotherapy, Drug: Cyclophosphamide (CPA) Phase 1 0 Merck KGaA NCT00960115 Study of EMD531444 in Subjects With Stage III Unresectable Non-small Cell Lung Cancer (NSCLC) Following Primary Chemoradiotherapy EMR063325-009 December 2008 May 2014 Non-small Cell Lung Cancer Biological: cyclophosphamide + EMD531444 + BSC, Biological: Saline + Placebo + BSC Phase 1, Phase 2 205 Merck KGaA, Merck Serono Co., Ltd., Japan The 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 shows the following results: 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 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. Merck Serono made the recommendation to stop the investigational treatment for patients in the EMR 63325-009 study in Japan.Merck Discontinues Clinical Development Program of Tecemotide as a Monotherapy in Stage III Non-Small Cell Lung Cancer - Merck KGaA Press release from 12 Sept 2014 EudraCT: 2011-004822-85 A prospective, open, randomized, phase-II study of a therapeutic cancer vaccine (L-BLP25, Stimuvax) in the pre-operative treatment of women with primary breast cancer ABCSG-34 / EMR 63325-603 Jan 2012 May 2014 Breast Cancer L-BLP25 (Stimuvax), Cyclophosphamide (CPA), LETROZOLE, EPIRUBICIN, DOCETAXEL Phase 2 400 ABCSG (Austrian Breast & Colorectal Cancer Study Group) 8 May 2012Startschuss für innovative Brustkrebs-Impfstudie ABCSG-34 Enrollment expected to be completed in May 2014 First results available end of 2014 26 Sept 2014ABCSG 34: Randomisierung beendet!