Oncolytics Biotech Inc ONCY

mRNA vaccine company Phase 2 trial fails on wrong biomarker

[Noteable]

April 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

[Noteable]

Gritstone's disappointing result puts into doubt Granite's chances of an accelerated approval; Gritstone previously hoped to pursue this based on molecular response data, which has drawn a blank. The company now intends to use PFS as the primary endpoint in a future pivotal study.  This shift in endpoint is surely down to Granite's complete failure to show a molecular

[Azzak34]

https://investors.biontech.de/news-releases/news-release-details/three-year-phase-1-follow-data-mrna-based-individualized Have a read folks. 

[Noteable]

As is happening with Candel Therapeutics, this BioNTech / Genentech collaboration is in resected pancreatic ductal adenocarcinoma (“PDAC”) not metastatic PDAC.

[Noteable]

AACR 24 -  BioNTech’s cancer vaccine in a phase 1 trial, patients with a difficult-to-treat type of pancreatic cancer continue to have T-cell responses. The long-term follow-up data from the early-stage trial show that eight out of 16 patients continue to enjoy an immune response up to three years after administration, as measured by activated T cells. Persistence of these T cells

[Noteable]

May 03, 2024 - Moderna has combined its mRNA vaccine with Merck's (MSD) immune checkpoint inhibitor Keytruda for the treatment of cancer. "Moderna’s foray into cancer is led by mRNA-4157’s use in patients with high-risk melanoma and non-small cell lung cancer on top of Keytruda. Since the start of the year, Moderna has seemingly coalesced around submitting the therapy for accelerated

[itntdf]

this is why oncy is in front of, not behind, the eight ball.  oncy has already ramped up its manufacturing capacity: That’s contingent on substantially enrolling the phase 3 melanoma study, which would serve as the confirmatory trial, and building up manufacturing capacity at a Marlborough, Massachusetts site. 

[Noteable]

In May 2024 Moderna announced "Moderna’s foray into cancer is [being] led by mRNA-4157’s use in patients with high-risk melanoma and non-small cell lung cancer on top of Keytruda." Moderna was planning on submitting the mRNA therapy for accelerated approval as a melanoma treatment, without recogizing that melanoma is a cancer that is neither rare or without an unmet treatment need,