Therapeutic cancer vaccines – there’s a new kid on the block
MUC-1
Near the front of the queue is Merck Serono’s Stimuvax, in a phase III registration trial for stage III unresectable non-small-cell lung cancer. The vaccine showed a small survival benefit at phase II, when it was trialled in 171 patients with later stage disease – stage IIIb/IV. But when the results for the locoregional stage IIIb patients were looked at in isolation, patients with the vaccine showed an additional 17 months survival over the control arm. “If you are treating patients with NSCLC this is really outstanding,” comments Oliver Kisker, head of Merck’s Global Clinical Development Oncology unit. The phase III eligibility criteria were therefore adjusted to include only patients with stage III unresectable disease. If the phase III results bear out the promising phase II data, and if the trial remains on track, Kisker believes Stimuvax could be the next vaccine to make it to market. “Certainly it has the potential to be the first active anti-cancer vaccine – true anti-cancer vaccine,” he says.
Stimuvax primes the immune system to lock on to MUC-1 (or mucin-1), which was one of the antigens used as a target in the very early experiments with immunotherapy done in the 1970s by Cancer Research UK, among others. Because MUC-1 is present in a high proportion of tumours not only in NSCLC, but also breast, prostate, colorectal, ovarian and other cancers, the hope is that if and when the treatment gets approval for lung cancer, it will be possible to take the vaccine forward across a number of other cancers as well.
Merck Serono obtained the exclusive worldwide rights for development and commercialisation of Stimuvax from the former Canadian and now American biotech Oncothyreon, who did the early development under the name L-BLP25. Growing confidence in the therapeutic potential of MUC-1 targeted vaccines is also seen, for instance, in the decision by Novartis to sign a $10?million deal with the French biotech Transgene, for exclusive development and commercialisation rights on a similar vaccine, TG4010, also in trials for use in NSCLC.
Unlike some cancer antigens, MUC-1 is also expressed by normal secreting cells – in the intestines, for instance – giving rise to the theoretical possibility that an anti-MUC-1 vaccine could trigger an autoimmune response and turn the body’s immune system against itself. However, ten years of experience using the vaccine in more than 1000 patients seems to indicate that the vaccine is selective for tumour MUC-1 expression, says Kisker. “It has not shown any side-effects that point to unwanted activity against the physiological expression of MUC-1.”
The Stimuvax NSCLC trial was put on temporary hold in March this year, when a myeloma patient developed encephalitis after receiving the vaccine. “We worked very closely with the FDA, and with the treating physician and neurology specialists. But overall it remains completely unclear what happened here, so we cannot rule out that Stimuvax might have had a role. We have not seen anything like this elsewhere, so we just don’t know,” said Kisker. So far there have been no reports of any MUC-1 expression in the tissue of neural or central nervous system organs.
Merck got the go ahead to resume their NSCLC trial in June with some additional safeguards in place, and Kisker remains confident that cancer vaccines are on track to join established cancer therapies. “These types of immunotherapies have the potential to become effective and low toxic treatments in the future. In the past it has been shown that development is not that easy, and we must be prepared for setbacks also in ongoing research, because we don’t understand fully all the details of the factors that are required to generate an effective immunotherapy. I think, in principle, all these therapies, like MAGE-A3 and other cancer vaccines currently in phase II and III, have the potential to become effective treatments in the future. We need to await the results from the clinical trials.”
“These type of immunotherapies have the potential to become effective and low toxic treatments in the future”
