A Phase 3 trial comparing IO Biotech’s cotton cancer vaccine data to Merck’s blockbuster oncology drug Keytruda proved unsuccessful in defeating Keytruda, and the company is focusing on yet another way to approval.
Patients took part in a global study of 407 with unresectable or metastatic melanoma to compare the combination with Keytruda to the drug alone as an initial treatment.
In evaluating the phase 3 study primary endpoint, progression-free survival (PFS), IO referenced an early and sustained separation of progression-free survival (PFS) curves between the two groups. The hazard ratio of 0.77 was, however, in the threshold of statistical significance with a P value of 0.056, as an August 11 release indicated.
Nevertheless, given that the Cylembio combo showed a median PFS of 19.4 months compared to the 11 months of the Keytruda group, the biotech was eager to present statistics that lent credence to its argument of why it should be approved. This involved the post-hoc analysis of PFS within the 371 patients who were untreated with prior anti-PD-1 treatment, who showed a nominal p value of 0.037.
Although the overall survival data are not mature, IO reported that a trend towards an improvement has already been observed, with more precise data expected within the six to nine months. This more positive OS trend is, said Qasim Ahmad, the Chief Medical Officer of the company, “encouraging, with the combination arm showing a better trend (favourable) across almost every subgroup.”
At least the topline failure has not stopped IO, which said it plans to go to the FDA in the fall to discuss the totality of data and what should be done next on an approval application.
In this study, there was a very promising progression-free survival and encouraging trend in overall survival in patients treated with Cylembio, according to the National Chairman of IO CEO Mai-Britt Zocca.
“This large and sustained clinical effect across subgroups further reinforces our belief in Cylembio, and its potential as a treatment option in advanced melanoma patients,” Zocca said. We anticipate discussing with the FDA the possibility of establishing a potential route of approval on the basis of these data.
Cylembio is a combination of two off-the-shelf vaccines based on IOs T-win platform, unlike the high-profile personalized vaccines to treat cancer that are under development by mRNA companies Moderna and BioNTech. This is done to activate T cells against cancer cells in the tumor microenvironment.
According to IO, it has promoted the platform as a highly differentiated mechanism of action displaying clinical activity without further considerable alternative toxicity when given in combination with a recognized anti-PD-1 therapy.