Imvax has shrugged off the failure of its phase 2b brain cancer trial to hit its primary endpoint, reporting evidence of improved overall survival (OS) and making a beeline for the FDA.
The study compared IGV-001 to placebo in 99 newly diagnosed glioblastoma patients. IGV-001 consists of personalized whole-tumor-derived cells and an antisense oligonucleotide in implantable biodiffusion chambers. The treatment is designed to trigger a tumor-specific immune response to improve outcomes in patients with the highly aggressive brain cancer. All patients received standard of care therapy.
Progression-free survival (PFS) was statistically no longer in the IGV-001 arm than in the placebo cohort, causing the study to miss its primary endpoint. Imvax, a 2020 Fierce 15 honoree, buried news of the primary endpoint miss deep in its press release and focused instead on its OS data.
Median OS in the IGV-001 cohort was 20.3 months, compared to 14 months in the placebo group. The biotech said the OS improvement of 6.3 months, or 45%, is clinically meaningful, but made no comment on the statistical analysis of the secondary endpoint in its press release.
With no patients on IGV-001 experiencing drug-related serious adverse events, Imvax has told the FDA it plans to file a request to discuss the regulatory pathway for the drug candidate. The failure on the primary endpoint is a blemish on the data, but the hit on OS may override the miss on PFS. FDA guidance states OS is usually the preferred endpoint and considered the most reliable measure.
Imvax’s 6.3-month improvement in median OS compares favorably to the data that support the current standard of care. Adding the chemotherapy drug temozolomide, which Merck & Co. sells as Temodar, to radiotherapy increased median OS from 12.1 months to 14.6 months. The FDA approved the drug in the indication on the strength of the 2.5-month improvement in 2005.
Since then, multiple drugmakers have tried and failed to improve on temozolomide plus radiotherapy. Bevacizumab, which Roche sells as Avastin, improved PFS but failed on OS. Northwest Biotherapeutics reported a significant improvement in OS in patients taking its dendritic cell vaccine DCVax-L. However, independent experts flagged potential concerns with the trial design, and the drug is yet to win approval.
With drugmakers failing to move the needle, device company Novocure provided the only progress in the treatment of glioblastoma of the past 20 years. The company linked the tumor treating fields device Optune to a median OS of 20.9 months, compared to 16 months for the control group. Real-world studies have identified barriers to initial and ongoing use of the device.