Tecemotide

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Tecemotide
other names
  • Human mucin-1 (carcinoma-associated mucin, episialin CD227) - (107-131) -peptide (sequence 40 times repeated) fusion protein with 6-N-hexadecanoyl-L-lysylglycine ( WHO )
  • BLP-25
  • Emepepimut-S ( USAN )
Mass / length primary structure 27 amino acids , 2.8 k Da
Identifier
External IDs
Drug information
DrugBank DB12568
Drug class Cancer vaccine , antineoplastic

Tecemotide (also known as the liposomal cancer vaccine BLP25 ) is a therapeutic vaccine (vaccine) of the MUC1 type that was tested in oncology (cancer medicine) in clinical phase III against non-small cell lung cancer (NSCLC) and against advanced or inoperable breast cancer .

Tecemotid was developed by the small Canadian biotech company Biomira (now Oncothyreon ). The Merck KGaA acquired the exclusive worldwide licensing rights except for Canada, where the companies will share the rights. From 2007 Tecemotid was further developed in Europe by Merck KGaA, in the USA by Merck subsidiary EMD Serono Pharmaceuticals. In 2014, Merck announced that it would discontinue research on the drug because expectations regarding its effectiveness had not been met.

construction

Schematic structure of the liposomal BLP25. The antigen, made up of 27 amino acids, is conjugated with the adjuvant lipid A and integrated into the membrane of the liposome. The red, thread-like structures on the surface of the liposome are supposed to represent the antigen.

Tecemotid is an artificially produced peptide made up of 27 amino acids that is chemically linked to monophosphoryl lipid A (MPL) and is integrated into the membrane of a lipsome. The MPL serves as an adjuvant . The amino acid sequence is in the one -letter code S T A P PA H G V TSAP D T R PAPGSTAPP, followed by a palmitylated lysine for binding to biomembranes and a glycine .

Mechanism of action

Tecemotid is designed to induce an immune response to MUC1-expressing tumor cells (active immunotherapy ). MUC1 is a tumor antigen which is expressed to a high degree on frequently occurring tumors, for example in bronchial , breast or colorectal cancer . The liposomal shell increases the recognition rate of the cancer antigen by the immune system and facilitates the release of the active ingredient at the target site.
As a response of the immune system, vaccination can trigger the binding of cytotoxic T cells ( killer cells ) to tumor cells with overexpressed MUC1. This can inhibit tumor growth.

Clinical testing

Tecemotide was in clinical trials. On 26 February 2007, the first patient in the global Phase III study was START ( S timulating T argeted A ntigenic R esponses T o NSCLC ). locked in. START examined the efficacy and safety of tecemotide in approximately 1,300 patients in unresectable non-small cell lung cancer (NSCLC) stage III. In 2004 the FDA granted Tecemotid the status of the accelerated test procedure ( Fast Track ).
On 22 June 2009, Merck KGaA announced the launch of a Phase III trial ( STRIDE , ST imulating immune R esponse I n a D vanced br e ast cancer known with over 900 patients with inoperable advanced breast cancer from over 30 countries).
On December 10, 2009, another phase III study with Tecemotid was started. The study called INSPIRE ( Stimuvax trial I n Asian NS CLC P atients: Stimulating I mmune RE sponse ) was conducted with about 420 patients with advanced non-small cell lung cancer from five different Asian countries.

In March 2010, after consulting the FDA, Merck suspended all studies with tecemotide after a patient fell ill with encephalitis . On June 17, 2010, the two studies on the treatment of NSCLC were resumed; the STRIDE study was suspended. On April 7, 2014, the start of a phase III START2 study with tecemotide in the indication of non-small cell lung cancer was announced.

Results from clinical trials

In April 2006, final median survival data were obtained for the vaccine-treated subgroup of patients with stage IIIB locoregional NSCLC. It was 30.6 months compared to 13.3 months for patients at the same stage who had not received the vaccine.

In September 2007 patient survival data from this study was published. In the patient group treated with Tecemotide in addition to the best therapeutic support (BSC = Best Supportive Care ), more than twice as many patients were still alive after three years as in the group with BSC alone (49% or 17 Patients compared with 27% or 8 patients). This corresponds to a 45% reduction in mortality .

A randomized, double-blind, placebo - controlled , multicenter Phase III study "START" ( Stimulating Targeted Antigenic Responses to NSCLC ) with over 1,300 patients in approx. 30 countries with documented inoperable NSCLC in stage IIIA or IIIB followed the phase II study on.

The main side effects observed in the phase II study were flu-like symptoms, gastrointestinal complaints and reactions at the vaccination site.

On December 19, 2012, it was announced that the primary endpoint of the START study , a statistically significant improvement in overall patient survival, had not been achieved. However, clear treatment effects could be observed in certain subgroups of patients. Further evaluations were intended to investigate the potential benefit-risk profile of L-BLP25 in certain patient groups.

On August 18, 2014, Oncothyreon published an SEC announcement in which Oncothyreon reported that Merck KGaA had announced that the Phase 1/2 clinical trial EMR 63325-009, in which Tecemotide was using a placebo in Japanese patients Lung cancer (phase III NSCLC) is compared, has not reached the primary endpoint, nor the secondary endpoints. Merck has announced that it is ceasing to enroll Japanese patients in this trial and that Japan will not be included in the Phase III program. Furthermore, Merck will investigate the effects on the ongoing Tecemotid program.

On September 12, 2014, Merck announced that it would discontinue development of Tecemotid based on the Japanese study results.

literature

  • S. von der Weiden: Vaccination against cancer. In: Welt am Sonntag on May 27, 2012
  • S. North and C. Butts: Vaccination with BLP25 liposome vaccine to treat non-small cell lung and prostate cancers. In: Expert Rev Vaccines 4/2005, pp. 249-257. PMID 16026241
  • R. Sangha and S. North: L-BLP25: a MUC1-targeted peptide vaccine therapy in prostate cancer. In: Expert Opin Biol Ther 7/2007, pp. 1723-1730. PMID 17961094
  • C. Butts et al: Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. In: J Clin Oncol 23/2005, pp. 6674-6681. PMID 16170175
  • SA North et al .: A pilot study of the liposomal MUC1 vaccine BLP25 in prostate specific antigen failures after radical prostatectomy. In: J Urol 176/2006, pp. 91-95. PMID 16753376
  • J. Nemunaitis and J. Nemunaitis: A review of vaccine clinical trials for non-small cell lung cancer. In: Expert Opin Biol Ther 7/2007, pp. 89-102. PMID 17150021
  • M. Palmer et al: Phase I study of the BLP25 (MUC1 peptide) liposomal vaccine for active specific immunotherapy in stage IIIB / IV non-small-cell lung cancer. In: Clin Lung Cancer 3/2001, pp. 49-57. PMID 14656392

Web links

Individual evidence

  1. ↑ a b Merck KGaA: Phase III study with the cancer vaccine Stimuvax begins. Press release from Merck KGaA, February 26, 2007 (PDF; 127 kB).
  2. ↑ CC Schimanski, M. Moehler et al .: LICC: L-BLP25 in patients with colorectal carcinoma after curative resection of hepatic metastases - a randomized, placebo-controlled, multicenter, multinational, double-blinded phase II trial. (PDF; 1.2 MB) In: BMC Cancer. Volume 12, 2012, 144, doi: 10.1186 / 1471-2407-12-144
  3. ↑ CW Cluff: Monophosphoryl Lipid A (MPL) as an Adjuvant for Anti-Cancer Vaccines: Clinical Results. In: J.-F. Jeannin (Ed.): Lipid A in Cancer Therapy. Springer publishing house, 2009.
  4. ^ R. Sangha and C. Butts: L-BLP25: a peptide vaccine strategy in non small cell lung cancer. In: Clin Cancer Res 13/2007, pp. 4652-4654. PMID 17671159
  5. ↑ WHO Drug Information, Vol. 26, No. 4, 2012; Proposed INN: List 108
  6. ↑ NSCLC study
  7. ↑ G. Schrimpf: Merck Initiates Phase III Study of Stimuvax in Breast Cancer. (PDF; 39 kB) Press release from Merck KGaA dated June 22, 2009
  8. ↑ Merck starts phase III INSPIRE study with Stimuvax in Asian patients with advanced NSCLC. In: bionity.com. December 11, 2009. Retrieved May 17, 2017 .
  9. ↑ G. Schrimpf: Merck continues clinical program with Tecemotide in lung cancer. (PDF; 32 kB) Press release from Merck KGaA dated June 17, 2010
  10. ↑ Bartels C .: Merck Serono starts phase III study START2 with Tecemotide in the indication of stage III non-small cell lung cancer Press release from Merck KGaA dated April 7, 2014.
  11. ↑ Announcement from Merck KGaA ( Memento of the original from October 21, 2007 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.merck.de
  12. ↑ a b c Press release from Merck KGaA: Phase II study with therapeutic cancer vaccine Stimuvax® provides positive three-year survival data for patients with lung cancer , from September 5, 2007  ( page no longer available , search in web archives )  Info: Der Link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: Toter Link / www.merck.de  
  13. ↑ Merck: Phase III study with L-BLP25 (Stimuvax) in patients with non-small cell lung cancer missed the primary endpoint.  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. Merck KGaA press release dated December 19, 2012 (PDF; 30 kB).@1@ 2Template: Toter Link / www.merckserono.de  
  14. ↑ Oncothyreon's 8-K SEC announcement of August 18, 2014 ( Memento of the original of August 21, 2014 in the Internet Archive ) Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / ir.oncothyreon.com
  15. ^ Company: Merck discontinues development of lung cancer drug Tecemotide. At: focus.de on September 12, 2014