IO Biotech’s cancer vaccine has “narrowly” failed to beat Merck's blockbuster oncology drug Keytruda in a phase 3 melanoma trial, but the company remains hopeful of a path to approval.
The New York-based biotech evaluated its therapeutic vaccine, called Cylembio, in combination with Keytruda against Keytruda alone as a first-line treatment in a global trial of 407 patients with unresectable or metastatic melanoma.
When it came to assessing the primary endpoint of progression-free survival (PFS), IO pointed to an “early and sustained separation of PFS curves” between the two cohorts. However, the hazard ratio 0.77 equated to a P value of 0.056, just missing the threshold for statistical significance, according to an Aug. 11 release.
Still, with a median PFS of 19.4 months in the Cylembio combo cohort compared to 11 months for the Keytruda group, the biotech was keen to highlight data that backed up its case for approval. This included a post-hoc analysis of PFS of the 371 patients who hadn’t received prior anti-PD-1 treatment, who demonstrated a nominal p value of 0.037.
While the overall survival data is not yet mature, IO said a “trend toward an improvement” has already been observed, with more accurate data due in the next six to nine months. The company’s chief medical officer Qasim Ahmad, M.D., said this “encouraging” OS trend “favor[s] the combination arm across virtually all subgroups.”
Undeterred by the top-line fail, IO said it still plans to head to the FDA in the fall “to discuss the totality of data” and determine next steps for submitting an approval application.
“In this study, we observed a highly encouraging improvement in progression-free survival and consistent trend in overall survival in patients treated with Cylembio,” IO CEO Mai-Britt Zocca, Ph.D., explained in an Aug. 11 release.
“The magnitude and durability of clinical effect observed consistently across subgroups supports our confidence in Cylembio and its potential as a treatment for advanced melanoma patients,” Zocca added. “We look forward to engaging with the FDA to determine a potential path to approval based on these data.”
Unlike high-profile personalized cancer vaccines being developed by mRNA companies Moderna and BioNTech, Cylembio is a combination of two off-the-shelf vaccines derived from IO’s T-win platform. The aim is to stimulate T cells against tumor cells in the tumor microenvironment.
IO has touted the platform as having a “highly differentiated mechanism of action [that] has demonstrated clinical activity without additional significant systemic toxicity when administered in combination with an approved anti-PD-1 therapy.”