Following in the path of other cancer vaccines that have already lived up to low expectations, Stimuvax has been revived to try again. Merck KGaA (MKGAY.PK) made the surprise announcement today that it would put the project, now called tecemotide, through another large phase III trial to try and replicate results that had emerged in a subgroup of the failed Start study.
That subgroup generated some intriguing data; at 800 patients strong investigators called it the largest clinical trial conducted in stage III non-small cell lung cancer patients in its own right, and the only one to demonstrate a significant survival benefit. A specific chemo-radiation regimen appears to have produced much stronger responses; Merck now needs to work out whether the presence of tecemotide contributed anything to the effect.
Start tested tecemotide (also known as L-BLP25) in a maintenance setting, enrolling patients with unresectable, locally advanced stage III NSCLC who had stable disease after at least two cycles of platinum-based chemo-radiotherapy. They were then treated with either tecemotide or a placebo, to see if the immunotherapy would prolong survival. Five-year survival for patients with lung cancer at this stage is 10-25%.
However the initial chemo-radiotherapy given as standard of care in this setting can vary, and Merck had stratified patients getting two different regimens – those who received chemotherapy and radiation concurrently, or those who received them sequentially.
Hence the decision to run Start2, which will look almost identical to Start1, but enroll only patients who have received the concurrent regimen. The FDA has agreed a Special Protocol Assessment for the study, and Merck says it has received advice from the European Medicines Agency.
Merck does not why this subgroup seemed to respond much more strongly to tecemotide.
Although the project is a MUC-1 antigen-specific immunotherapy, the pivotal studies have not recruited or stratified patients based on their MUC-1 status. A spokesman for Merck could not confirm whether this would be different in Start2, saying only that the company would be seeking to understand the immunological response and look for potential predictive biomarkers.
Dr Butts also said patient selection might be a simpler explanation. Those who get selected for sequential chemo-radiotherapy are not really being treated with curative intent, he said. It is widely believed that immunotherapies are likely to work better in relatively healthier patients, and those are the patients being given concurrent chemo-radiation.
Although the subgroup on which this decision is based was large, many will still consider this a risky basis for further study. Some investors thought it was a risk worth taking: shares in Oncothyreon (ONTY), which licensed the drug to Merck and saw its valuation more than halve on news of the Start failure, were trading 22% higher this morning at $2.19; Merck KGaA stock was little changed. But, in the meantime, tecemotide will struggle to shake off the stain of past failure.
No comments:
Post a Comment