mRNA vaccine company Phase 2 trial fails on wrong biomarkerApril 02, 2024 - Gritstone bio’s gamble on a novel endpoint has backfired.
The primary endpoint looked at changes in ctDNA. On that measure, Gritstone’s drug combination was numerically worse than chemotherapy alone, with the molecular responses in the vaccine and control arms coming in at 30% and 41.7%, respectively.
All patients received induction and maintenance chemotherapy. Around half of the subjects also received Gritstone’s personalized neoantigen cancer vaccine, Bristol Myers Squibb’s Yervoy and Roche’s Tecentriq during the maintenance phase.
Gritstone picked ctDNA, rather than the widely used and accepted PFS, as its primary endpoint.
Consequently, the short-term circulating tumor DNA (ctDNA) biomarker response analysis did not demonstrate a difference in the 39 newly diagnosed, metastatic microsatellite-stable colorectal cancer (MSS-CRC) patients treated versus the 28 in the control arm.
Patients on the GRANITE mRNA vaccine regimen showed a molecular response of 30%, while the control arm came in at 41.7%. Gritstone pointed to the unanticipated continuation of the drop in ctDNA from induction chemotherapy in both arms, which generated similar short-term response rates.
“We simply got it wrong,” Gritstone CEO Andrew Allen said in a statement.
Gritstone recognized that median progression-free survival (mPFS) is the more appropriate endpoint / biomarker, which is one of the biomarker's / endpoints that ONCY has employed in its full platform of adaptive clinical trials involving pelareorep in combination with chemotherapy +/- immune checkpoint inhibitors.
The Gritstone's Phase 2 mRNA results have implications for Moderna's personalized mRNA vaccine + keytruda combination in the treatment of cancer, since Moderna is seeking to demonstrate improvement in recurrance-free survival and distant metastatic-freee survival with individualized neoantigen therapy approach as an endpoint.
https://www.fiercebiotech.com/biotech/gritstone-ground-down-phase-2-cancer-vaccine-fail-sparking-race-against-cash-gather-more
https://www.biospace.com/article/gritstone-fails-cancer-vaccine-trial-plans-phase-iii-and-public-offering-/
https://www.nature.com/articles/d41591-023-00072-0