Stimuvax, first therapeutic vaccine for lung cancer, to start Phase III trial

ASCO 2006

Stimuvax, first therapeutic vaccine for lung cancer, to start Phase III trial

Stimuvax (L-BLP 25), a therapeutic vaccine in development for non-small cell lung cancer (NSCLC), should enter Phase III testing this autumn. The START (Stimulating Targeted Antigenic Response to NSCLC Trial ) plans to recruit over 1300 patients with stage III unresectable disease from more than 140 centres in North America and Europe. Patients will receive an initial round of chemo/radiation therapy and if they show a response, or exhibit stable disease, they will be randomised in a ratio of 2:1 to receive the vaccine or placebo.

The phase III trial will compare Stimuvax against placebo alongside chemo/ radiotherapy in  “real-world” practice setting.  Centres will be permitted to administer chemotherapy and radiation therapy simultaneously or in sequence as they wish.  Treatment  administered will consist of  a single iv dose of 300mg/m2 cyclophosphamide followed by eight weekly subcutaneous Stimuvax immunisations.  Maintenance immunisations will follow at 6-weekly intervals. Study endpoints are time to progression, overall survival and quality of life.

Describing the vaccine, Dr Charles Butts senior medical oncologist at the Cross Cancer Institute in Edmonton, Canada and the Canadian regional principal investigator of the trial, said its major component is the highly antigenic, synthetic human MUC I protein consisting of a 20-amino acid tandem repeat sequence on its extracellular domain.  “Although MUC I is expressed on normal epithelial tissue as well as NSCLC tumour cells, the tumour variety is abnormally glycated and therefore able to trigger an immune response.“ 

The other, immunoadjuvant, component of the vaccine is MPL (monophosphoryl lipid A) a non-specific stimulant designed to prime the immune system and facilitate take-up of the vaccine.  Both are enclosed in a liposomal vehicle.  Vaccine is injected subcutaneously at four points of the body and taken up by cytotoxic T lymphocytes and T-helper cells which potentiate the immune response. The idea is that the vaccine will prevent relapse by mopping up residual cancer cells that survive chemoradiation.

The vaccine is extremely well tolerated, Dr Butts commented.   “One of the beauties of therapeutic vaccines is that they produce minimal side effects”.  A few patients experience redness at the injection site or mild fever and transitory flu-like symptoms.  

Results of an earlier open-label phase Ilb trial involving 171 patients with stage IIIb or staqe IV NSCLC showed median survival was 30.6 months among vaccine-treated patients compared to 13.3 months among controls. (Five-year survival in NSCLC is normally 15 to 20 per cent with a median survival time of 17 to 18 months.)
     “Currently almost 50 per cent of the vaccinated group are still alive compared to 25 per cent of control group patients.  The magnitude of the difference is striking” he remarked.
    If the phase III trial proves positive, the vaccine may be studied in earlier stages of lung cancer following resection, said Dr Butts.  It could also be investigated at other cancer sites. “The MUC 1 protein is found on breast, colon and prostate tumours and even in multiple myeloma, so the vaccine has huge potential.”

L-BLP-25 is being developed in Europe by Merck KGaA and in North America by Biomera Inc and EMD Pharmaceuticals.

Olwen Glynn Owen
glynnowen@macline.co.uk

To see more features by Olwen Glynn Owen follow this link to his first feature article and scroll to the end for a list:
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