According to results from the phase 2 GO-010 study, the addition of GRANITE, a personalized neoantigen-targeting immunotherapy regimen using chimpanzee adenovirus and self-amplifying mRNA vaccines, to standard first-line therapy demonstrated promise among patients with metastatic microsatellite stable colorectal cancer. 

These results were presented by Joel Hecht, MD, University of California, Los Angeles, California, at the 2025 ASCO Gastrointestinal Cancers Symposium in San Francisco, California.  

In this study, 104 newly diagnosed patients with 20 neoantigens were randomized on a 1-to-1 basis to receive standard induction chemotherapy either alone (n = 53) or in combination with the GRANITE regimen (n = 51). Eligible ctDNA evaluable patients (n = 67) were classified by having high (n = 43) or low (n = 24) disease burden. The primary end point of this study was molecular response, with other key end points including progression-free survival (PFS), overall survival (OS), and safety. 

At analysis, patients in the GRANITE arm experienced improved PFS compared to patients in the standard arm (hazard ratio [HR], 0.73; 90% confidence interval [CI], 0.44 to 1.21). Greater clinical benefit was observed among patients with low disease burden compared to patients with high disease burden. Among patients with low disease burden, PFS rate was 41% in the GRANITE arm and 21% in the standard arm. Neoantigen-specific t-cell response was observed in 100% of patients in the GRANITE arm. Molecular response based on a reduction in ctDNA was 39% in the GRANITE arm and 40% in the standard arm. The most common treatment-related adverse events occurring in ≥ 20% of patients included pyrexia and influenza-like symptoms. No patients discontinued treatment due to treatment-related adverse events.

“This randomized study shows GRANITE may benefit patients, especially those with low burden disease, in this front line setting of metastatic MSS-CRC that has not benefited from immunotherapy,” concluded Dr Hecht et al. “Additional studies may identify better end points and clinical settings for this and other immunotherapy regimens.” 

Source: 

Hecht JR, Spira AI, Nguyen AV, et al. A randomized phase 2 study of an individualized neoantigen-targeting immunotherapy in patients with newly diagnosed metastatic microsatellite stable colorectal cancer (MSS-CRC). Presented at The 2025 ASCO Gastrointestinal Cancers Symposium. January 23-25, 2025. Abstract LBA13