Gritstone bio, Inc. announced updated results from the Phase 1/2 study evaluating the safety, immunogenicity, and clinical activity of GRANITE individualized neoantigen immunotherapy (heterologous prime-boost in combination with PD-1 checkpoint inhibitor Opdivo® [nivolumab] and subcutaneous anti-CTLA-4 antibody Yervoy® [ipilimumab]) in advanced solid tumors. The data were presented during a mini-oral presentation by investigator and Associate Professor of Medicine at the University of Chicago, Dan Catenacci, MD, as part of the European Society of Medical Oncology (ESMO) Annual Meeting. In the 26 patients treated in the study with metastatic solid tumors largely focused on MSS-CRC and gastro-esophageal adenocarcinoma (GEA), GRANITE immunotherapy demonstrated good tolerability, consistent and potent immunogenicity (CD8+ neoantigen-specific T cell induction in all subjects), and objective evidence of efficacy as measured by reduction in ctDNA (molecular response). In particular, MSS-CRC patients exhibited “cold” tumors at baseline, with low PD-L1 and IFN-g expression and low tumor mutational burden. Based on these data, Gritstone has discussed the registrational path with the U.S. Food & Drug Administration (FDA), and is advancing GRANITE into a randomized, controlled, phase 2/3 clinical trial (single protocol) for the maintenance treatment of newly diagnosed metastatic MSS-CRC patients who have completed FOLFOX-bevacizumab induction therapy. Additionally, the company will conduct a separate randomized, controlled phase 2 trial evaluating GRANITE in the adjuvant setting for stage II/III MSS-CRC patients who are ctDNA+ after definitive surgery. The trials are expected to begin in the first half of 2022. The checkpoint inhibitors being used for these studies have not yet been disclosed. As of the August 5, 2021 data cutoff, the GRANITE Phase 1/2 study treated 26 patients; 14 in the Phase 1 dose escalation portion, and 12 in the Phase 2 portion across three tumor-specific expansion cohorts – MSS-CRC, gastroesophageal adenocarcinoma (GEA), and non-small cell lung cancer (NSCLC). All patients receive 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-CRC patients, where checkpoint inhibitors have shown minimal activity, GRANITE elicited a 44% molecular response rate in 9 evaluable patients (defined as a 50% or greater reduction in ctDNA from baseline) which is an increasingly well recognized objective efficacy biomarker for novel immunotherapy. Patients who demonstrated molecular response had median overall survival of >17 months (median not reached) whereas those without molecular response exhibited a median overall survival of 7.8 months, consistent with expected outcomes in 3rd line treatment of MSS-CRC. A confirmed complete RECIST response was observed in a GEA patient (ctDNA negative at baseline). Multiple patients remained on treatment for over 6 months with lack of confirmed disease progression including 2/9 MSS-CRC patients receiving treatment beyond 12 months and one patient currently at 11+ months, which contrasts sharply with the expected outcome for these patients. 50% of patients (3/6) had a slow decrease in volume of multiple pulmonary metastasis during the first year of therapy, even though these objective radiological responses did not meet RECIST criteria. These radiological observations were associated with prolonged time on study and decrease in biomarkers such as ctDNA.