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Vaccine Detail
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BLP25 liposomal vaccine (L-BLP25/tecemotide/Stimuvax®) |
| Vaccine Information |
- Vaccine Name: BLP25 liposomal vaccine (L-BLP25/tecemotide/Stimuvax®)
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Peptide vaccine
- Status: Clinical trial
- Host Species for Licensed Use: Human
- Antigen: 25-mer MUC1 (STAPPAHGVTSAPDTRPAPGSTAPP) (Palmer et al., 2001; Butts et al., 2011; Schimanski et al., 2012; Butts et al., 2014; Singer et al., 2020)
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Adjuvant:
Monophosphoryl lipid A (MPL) (Palmer et al., 2001; Butts et al., 2011; Schimanski et al., 2012; Butts et al., 2014; Singer et al., 2020)
- Immunization Route: subcutaneous injection
- Description: A liposomal lipopeptide subunit vaccine consisting of a synthetic 25-amino acid BLP25 lipopeptide STAPPAHGVTSAPDTRPAPGSTAPPK(Pal)G homologous to the MUC1 tandem repeat core peptide with a C-terminal palmitoyl-lysine residue enabling integration into the lipid bilayer, formulated with monophosphoryl lipid A (MPL) adjuvant and three liposomal lipids (dipalmitoyl phosphatidylcholine, cholesterol, dimyristoyl phosphatidylglycerol) (Palmer et al., 2001; Schimanski et al., 2012), administered as 930 µg subcutaneous injections [Ref6928:Butts et al., 2011; note: earlier trials declared 1,000 µg due to a density measurement error subsequently corrected) preceded by a dose of cyclophosphamide (300 mg/m² IV) to reduce T-suppressor cell activity (Palmer et al., 2001). The vaccine induces primarily cellular immunity: MHC class I–restricted CD8+ CTL responses against MUC1-expressing tumor targets were detected in 5 of 12 evaluable NSCLC patients in the phase I trial, with specific lysis ranging 15–83%, and no significant humoral response, consistent with the Th1-biased liposomal design (Palmer et al., 2001). In a phase IIB trial in stage IIIB/IV NSCLC (n=171), median overall survival was longer with L-BLP25 versus best supportive care (17.2 vs. 13.0 months; HR 0.745), with a significantly improved 3-year survival rate (31% vs. 17%; p=0.035); the strongest signal emerged in stage IIIB loco-regional disease (median OS 30.6 vs. 13.3 months; HR 0.548; 3-year survival 49% vs. 27%) (Butts et al., 2011). In the phase III START trial (n=1,239 mITT), the primary endpoint of overall survival was not met (25.6 vs. 22.3 months; HR 0.88), but a significant survival benefit was observed in the subgroup receiving concurrent chemoradiotherapy (30.8 vs. 20.6 months; HR 0.78; p=0.016) (Butts et al., 2014). No benefit was demonstrated in HER2-negative early breast cancer (ABCSG 34; n=400; RCB 0/I 36.4% vs. 31.9%) despite near-universal MUC1 expression, suggesting tumor immunogenicity rather than antigen expression is the limiting factor for vaccine efficacy (Singer et al., 2020).
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| References |
Butts et al., 2011: Butts C, Maksymiuk A, Goss G, Soulières D, Marshall E, Cormier Y, Ellis PM, Price A, Sawhney R, Beier F, Falk M, Murray N. Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial. Journal of cancer research and clinical oncology. 2011; 137(9); 1337-1342. [PubMed: 21744082].
Butts et al., 2014: Butts C, Socinski MA, Mitchell PL, Thatcher N, Havel L, Krzakowski M, Nawrocki S, Ciuleanu TE, Bosquée L, Trigo JM, Spira A, Tremblay L, Nyman J, Ramlau R, Wickart-Johansson G, Ellis P, Gladkov O, Pereira JR, Eberhardt WE, Helwig C, Schröder A, Shepherd FA. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. The Lancet. Oncology. 2014; 15(1); 59-68. [PubMed: 24331154].
Palmer et al., 2001: Palmer M, Parker J, Modi S, Butts C, Smylie M, Meikle A, Kehoe M, MacLean G, Longenecker M. Phase I study of the BLP25 (MUC1 peptide) liposomal vaccine for active specific immunotherapy in stage IIIB/IV non-small-cell lung cancer. Clinical lung cancer. 2001; 3(1); 49-57; discussion 58. [PubMed: 14656392].
Schimanski et al., 2012: Schimanski CC, Möhler M, Schön M, van Cutsem E, Greil R, Bechstein WO, Hegewisch-Becker S, von Wichert G, Vöhringer M, Heike M, Heinemann V, Peeters M, Kanzler S, Kasper S, Overkamp F, Schröder J, Seehofer D, Kullmann F, Linz B, Schmidtmann I, Smith-Machnow V, Gockel I, Lang H, Galle PR. 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. BMC cancer. 2012; 12; 144. [PubMed: 22494623].
Singer et al., 2020: Singer CF, Pfeiler G, Hubalek M, Bartsch R, Stöger H, Pichler A, Petru E, Bjelic-Radisic V, Greil R, Rudas M, Maria Tea MK, Wette V, Petzer AL, Sevelda P, Egle D, Dubsky PC, Filipits M, Fitzal F, Exner R, Jakesz R, Balic M, Tinchon C, Bago-Horvath Z, Frantal S, Gnant M. Efficacy and safety of the therapeutic cancer vaccine tecemotide (L-BLP25) in early breast cancer: Results from a prospective, randomised, neoadjuvant phase II study (ABCSG 34). European journal of cancer (Oxford, England : 1990). 2020; 132; 43-52. [PubMed: 32325419].
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