Gritstone bio Releases Interim Phase 2 Data for GRANITE Immunotherapy in Metastatic MSS Colorectal Cancer

Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology enterprise, has publicized promising interim Phase 2 results from its ongoing study of GRANITE, an individualized neoantigen-targeting immunotherapy, aimed at treating frontline microsatellite stable colorectal cancer (MSS-CRC). This randomized, controlled trial is designed to assess the clinical benefits of GRANITE (GRT-C901/GRT-R902) when used as maintenance therapy in combination with immune checkpoint inhibitors along with fluoropyrimidine and bevacizumab, compared to the standard treatment of fluoropyrimidine and bevacizumab alone.

The progression-free survival (PFS) data have shown a positive impact for those receiving GRANITE, with a hazard ratio (HR) of 0.79 (95% CI, 0.42-1.50). The most significant benefits were noted among the 50% of patients with a lower disease burden at the start of the study, measured by circulating tumor DNA (ctDNA) (HR=0.62 [95% CI, 0.23-1.70]). Ongoing follow-up is essential to comprehensively evaluate the effects of GRANITE and to ascertain whether a sustained improvement in PFS is achievable. For the 20 patients who have not experienced disease progression (as per RECIST criteria), recent ctDNA assessments suggest potential benefits from GRANITE, with 12 out of 13 GRANITE patients showing stable ctDNA levels below the limit of quantitation, compared to 4 out of 7 control patients.

Andrew Allen, MD, PhD, Co-Founder, President, and CEO of Gritstone bio, expressed optimism about GRANITE's potential to enhance both progression-free and overall survival in MSS-CRC, a condition where continuous disease advancement is typical with existing treatments. Dr. Allen emphasized the evolving field of neoantigen-targeting immunotherapy, particularly for patients with lower disease volumes. He noted that patients with low ctDNA at the study's onset, indicating a relatively low disease burden, might benefit significantly from this immunotherapy. Success in immunotherapy often appears as a prolonged plateau in PFS and overall survival curves, which might be emerging in patients with lower disease burdens. He pointed out that the recent stable ctDNA measurements in most GRANITE patients are encouraging, as this pattern is uncommon in patients about to experience disease progression.

The interim data also indicated that the GRANITE treatment was generally well-tolerated, with no patients discontinuing due to adverse events. Common adverse effects were mild and included transient flu-like symptoms, typical of potent vaccines. Only one treatment-related serious adverse event (fatigue) was reported in the GRANITE group, with the patient continuing treatment after recovery.

Additionally, Gritstone bio announced that Raymond James has been appointed as a financial advisor to aid the company in exploring and reviewing strategic alternatives aimed at maximizing value. Gritstone does not plan to disclose further developments regarding these strategic explorations unless a definitive action is taken.

As of August 19, 2024, 104 patients were randomized for the study, with 69 patients (39 in the GRANITE arm and 30 in the control arm) included in the treated analysis. The demographics and clinical characteristics were well-balanced between the groups, with 80% of the patients having liver metastases. Thirty-five patients did not proceed to study treatment after oxaliplatin, mainly due to withdrawing consent, disease progression, or other reasons.

The emerging PFS benefit was observed across all GRANITE recipients, with a 21% relative risk reduction of progression or death compared to the standard of care (HR=0.79 [95% CI, 0.42-1.50]). Among those still in the study, 33% of GRANITE patients and 23% of control patients remained progression-free. The last ctDNA assessment indicated that 12 out of 13 GRANITE patients and 4 out of 7 control patients had ctDNA levels below the assay limit of quantitation.

This interim analysis suggests that GRANITE could be particularly beneficial for patients with a low disease burden at the start of the study, as indicated by a 38% relative risk reduction of progression or death in this subgroup (HR=0.62 [95% CI, 0.23-1.70]). Furthermore, functional neoantigen-specific T cells were observed in all tested GRANITE patients, with an apparent association between PFS and peak ex vivo ELISPOT responses, suggesting that these immune responses might be a surrogate for PFS.

Gritstone plans to discuss the PFS data with the FDA to determine the next steps for advancing GRANITE, including potential Phase 2 or 3 trials utilizing ctDNA levels as eligibility criteria.