Gritstone announces interim GRANITE study data

Gritstone announced interim Phase 2 data from the ongoing Phase 2 study evaluating GRANITE, its individualized neoantigen targeting immunotherapy, in frontline microsatellite stable colorectal cancer, or MSS-CRC. The randomized, controlled study is designed to evaluate the clinical benefit of maintenance therapy with GRANITE in combination with immune checkpoint inhibitors in addition to fluoropyrimidine/bevacizumab versus fluoropyrimidine/bevacizumab alone. Overall progression-free survival data show an encouraging benefit for GRANITE patients. As expected, the greatest benefit was observed in the 50% of patients with lower disease burden at study entry, as measured by circulating tumor DNA at study baseline. Continued follow-up is needed to fully assess GRANITE effects and determine whether a plateau of improved PFS is achieved. The most recent ctDNA assessments for the 20 patients who remain without disease progression were supportive of potential benefit from treatment with GRANITE: 12 of 13 GRANITE patients had stable ctDNA titers below the assay limit of quantitation; 4 of 7 control patients exhibited the same characteristic. Interim data demonstrated an emerging PFS benefit to all GRANITE recipients 21% relative risk reduction of progression or death with GRANITE vs. standard of care control in all treated population 33% GRANITE and 23% of control patients remain on study and free of progression. Last ctDNA assessment is below the assay LOQ in 12/13 GRANITE and 4/7 control patients. Clinical benefit was most notable in patients with low disease burden. 38% relative risk reduction of progression or death with GRANITE vs. SOC control with low ctDNA subgroup. Low baseline ctDNA is a likely prognostic and predictive factor. Immune data were consistent with clinical activity. Functional neoantigen-specific T cells were observed in all 16/16 GRANITE patients tested by ELISPOT. Association of PFS and peak ex vivo ELISPOT responses was apparent, suggesting that ex vivo ELISPOT may be a surrogate for PFS. GRANITE demonstrated a favorable safety and tolerability profile. No patients discontinued study treatment due to an adverse event. Common adverse events were the mild systemic and local effects associated with any potent vaccine, i.e. transient flu-like illness. One treatment-related serious AE occurred in the GRANITE arm. Gritstone plans to review the PFS data with FDA in the coming months and agree on next steps to advance GRANITE, including a potential Phase 2 or 3 trial using ctDNA levels as eligibility criteria.