Gritstone bio, Inc. announced that interim results from the Phase 1/2 trial of GRANITE, its individualized, vaccine-based immunotherapy candidate for solid tumor cancers, were published on August 15, 2022 in Nature Medicine. The paper, “Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results,” details results demonstrating that GRANITE generated strong, persistent, and functional tumor-specific CD4+ and CD8+ T cell responses that have potential broad applicability across a range of disease settings. The published data were originally presented at the European Society for Medical Oncology (ESMO) Congress 2021, and acted as the basis for launching two randomized, controlled studies of GRANITE, including a Phase 2/3 trial that has registrational intent (GRANITE-CRC-1L).
Since initiation of the Phase 1/2 study, Gritstone has followed study participants and observed increased overall survival (OS) in colorectal cancer (CRC) patients who demonstrated a molecular response (measured by a reduction in circulating tumor DNA [ctDNA] levels from baseline) versus those who did not. As of May 2022, median OS of this subgroup (treated third-line CRC patients who demonstrated a molecular response) exceeded 18 months with the median not yet reached. This compares to median OS of 7.8 months for patients who did not demonstrate a molecular response, results which are generally consistent with extensive prior data from patients receiving various third-line therapies.
Baseline characteristics of these two patient populations are similar. The Phase 1/2 study remains ongoing. GRANITE is now being evaluated in two randomized studies in earlier-stage disease; 1) GRANITE-CRC-1L (NCT05141721), a Phase 2/3 trial in newly diagnosed metastatic, microsatellite-stable colorectal cancer (MSS-CRC) that has registrational intent.
The first patient was treated in this study in July 2022, and initial results from this study are expected in the second half of 2023. 2) GRANITE-ADJUVANT (NCT05456165), a phase 2 study in patients with high-risk stage II/III colon cancer who are ctDNA+ after definitive surgery. Gritstone's neoantigen-based immunotherapies are engineered to elicit a significant T cell response (particularly CD8+ cytotoxic T cells) against mutation-derived tumor-specific neoantigens (TSNA), that Gritstone identifies using its proprietary artificial intelligence platform, EDGE™.
GRANITE is an individualized neoantigen-based immunotherapy and uses a priming adenoviral vector (GRT-C901) and self-amplifying mRNA vector (GRT-R902) to deliver personalized immunotherapy containing the relevant neoantigens. GRANITE was granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of MSS-CRC.