IO Bio plans cancer vaccine filing despite trial miss
IO Biotech's cancer vaccine Cylembio failed to hit the mark in a phase 3 melanoma trial – but the company hopes to file for approval regardless.
The company said that the study "narrowly missed" the primary endpoint of an improvement in progression-free survival (PFS) when Cylembio (imsapepimut and etimupepimut) was added to MSD's PD-1 inhibitor Keytruda (pembrolizumab) in previously untreated advanced melanoma patients.
Despite that, it plans to have discussions with the FDA in the coming months in the hope of proceeding with a marketing application before the end of the year. Investors seemed unimpressed with the idea, however, and shares in IO closed down 42% after the announcement.
Cylembio is an 'off-the-shelf' therapeutic cancer vaccine based on engineered peptides designed to invoke an immune response against melanoma cells. It is intended for use alongside checkpoint inhibitors like Keytruda, which remove a molecular brake on immune responses to tumours.
Topline results from the study showed what IO said is the longest median PFS observed in a phase 3 advanced melanoma trial, coming in at 19.4 months for the combination versus 11.0 months for Keytruda given as a monotherapy, despite missing statistical significance with a p-value of 0.056, with a trend towards improved overall survival (OS).
The New York biotech also pointed to what it said were impressive data in specific patient subgroups, such as a fivefold improvement in median PFS among melanoma patients with PD-L1-negative tumours. A post-hoc analysis of patients who were checkpoint inhibitor-naïve at enrolment also showed a PFS improvement from 19.4 months with Keytruda to 24.8 months, which just crossed the significance threshold (p=0.037).
"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," said Mai-Britt Zocca, IO's chief executive.
"We look forward to engaging with the FDA to determine a potential path to approval based on these data," she added. One issue facing the company could be the low number of US patients included in its phase 3 trial, at just 17 out of a total enrolment of more than 400, although most of the remainder were from Europe.
There are a lot of personalised cancer vaccines coming through the industry pipeline for melanoma, including mRNA-based candidates from Moderna (mRNA-4157/V940), BioNTech (BNT111), and Strand Therapeutics (STX-001), but IO's candidate has the advantage of being usable by all patients without the need for it to be customised to each patient. Another potential all-comer candidate is Scancell's SCIB1/SCIB1+, which recently performed well in a phase 2 trial.
Meanwhile, there is one vaccine-like product approved to treat melanoma in the US – Amgen's Imlygic (talimogene laherparepvec), although, that is an engineered oncolytic virus administered locally to melanomas that is designed to kill and break open the cancer cells, releasing material that can stimulate the immune system. First approved in 2015, Imlygic is a niche product and has never been a big earner, but it has shown dramatic benefits in some patients.
GlobalData has suggested that, if approved, Cylembio could make annual sales of around $495 million in 2031.
