Gritstone announced updated results from the Phase I/II during a mini-oral presentation at ESMO 2021. The study evaluated the safety, immunogenicity, and clinical activity of GRANITE individualized neoantigen immunotherapy (heterologous prime-boost in combination with PD-1 checkpoint inhibitor Opdivo and subcutaneous anti-CTLA-4 antibody Yervoy) in advanced solid tumors.
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. FDA has granted Fast Track Designation to Granite for the treatment of MSS CRC. At the data cutoff date of 5 August 2021, 26 patients were treated; 14 in phase I dose escalation portion and 12 in phase II portion across three tumor-specific expansion cohorts – MSS-CRC, gastroesophageal adenocarcinoma (GEA), and non-small cell lung cancer (NSCLC). All patients received Gritstone’s proprietary heterologous prime-boost consisting of Chimpanzee Adenovirus Vector (ChAdV) and Self-Amplifying mRNA (SAM) in combination with intravenous nivolumab and subcutaneous ipilimumab.
In MSS RCC a molecular response of 44% was elicited by ctDNA (circulating tumor DNA) analysis. The patients who demonstrated a molecular response had median OS of >17 months (median not reached) and in those without molecular response exhibited a median OS of 7.8 months.
“The unmet need in our many patients with metastatic colorectal cancer is profound –third-line therapy offers limited additional benefit and checkpoint inhibitors are ineffective in this setting. The early, but strikingly consistent, clinical and translational data from the Gritstone program are very encouraging, and the suggestion that immunologically cold tumors can become viable targets for the immune system could be a game-changer in treating MSS-CRC. I am excited to see how well GRANITE can perform in healthier, earlier-stage patients where we expect to see fewer patients’ progress rapidly before active immunotherapy.”
— Investigator and Director, Gastrointestinal Oncology Program at the University of Chicago
INSIGHTS: Based on these data Gritstone has discussed the registrational path with FDA and expects to begin a phase II/III clinical trial (single protocol) for the maintenance treatment of newly diagnosed metastatic MSS-CRC patients who have completed FOLFOX-bevacizumab induction therapy. Moreover, the company plans to conduct a separate phase II trial in adjuvant setting or stage II/III MSS-CRC patients who are ctDNA+ after definitive surgery. Both trials are expected to start in 1H of 2022.