On November 10, 2022 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, reported updated overall survival (OS) results from its Phase 1/2 study evaluating GRANITE, an individualized vaccine-based immunotherapy, for the treatment of advanced solid tumors (Press release, Gritstone Oncology, NOV 10, 2022, View Source [SID1234623670]). These results, along with results from a clinicopathologic analysis of metastatic MSS-CRC patients with and without a molecular response, will be presented via a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting.

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"The follow-up data from our Phase 1/2 study in patients with MSS-CRC who have received at least two prior lines of therapy continue to demonstrate an association between molecular response and overall survival," said Andrew Allen, M.D., Ph.D., Co-founder, President and Chief Executive Officer of Gritstone. "The median overall survival (MOS) in patients with MSS-CRC that had a molecular response has still not been reached and will now exceed 22 months; an additional four months since our last update in May 2022. This is a notable difference compared to the 6–7-month MOS typically observed in third-line MSS-CRC and the 7.8 month MOS in patients without a molecular response within our study. The clinicopathologic analysis shows MSS-CRC patients who achieve a molecular response do not have high tumor mutation burden, PD-L1 expression or high expression of IFNg-related genes. We are also observing molecular responses in patients with liver metastases, a subset that typically receives little benefit from immunotherapy. The recent publication of GRANITE Phase 1/2 results in Nature Medicine detail the program’s novel approach, and the data to date demonstrate its promise in hard-to-treat, late-line settings. The randomized Phase 2/3 GRANITE study in first-line CRC, where patients generally have more time to mount an immune response, is ongoing and preliminary data are expected in 4Q2023."

The Phase 1/2 study is evaluating the safety, immunogenicity, and clinical activity of GRANITE in combination with PD-1 checkpoint inhibitor, nivolumab and subcutaneous anti-CTLA-4 antibody ipilimumab in advanced solid tumors. This study enrolled and treated 29 patients with previously treated, metastatic solid tumors including patients with colorectal cancer, gastroesophageal adenocarcinoma, and non-small cell lung cancer. Of 13 patients with MSS-CRC, 6 experienced a molecular response defined as ≥30% reduction in circulating tumor DNA (ctDNA) and continue to have an overall survival advantage compared to those patients without a molecular response.

Updated OS data from GRANITE Phase 1/2:

6 of 13 treated patients with MSS-CRC had a molecular response and the observed median overall survival in this group will now exceed 22 months (median OS not yet reached versus 7.8 months in those without a molecular response). This compares to a median overall survival not yet reached and exceeding 18 months as reported in May 2022.
Clinicopathologic characteristics from GRANITE Phase 1/2:

4 of 6 patients with molecular response had liver metastasis.
All patients had PD-L1 expression <1% and low levels of IFNg-related gene expression.
Median tumor mutational burden was 2.9 and 3.6 mutations/MB in those with and without molecular response, respectively.
SITC presentation details are as follows:
Abstract 660: Clinicopathologic Characteristics of Patients with Metastatic Colorectal Cancer with Molecular Responses Following Treatment with an Individualized Neoantigen Vaccine Regimen
Date/Time: Friday, Nov. 11, 2022: 9:00am – 8:30pm EST
Session: Clinical Trials In Progress
Location: Boston Convention & Exhibition Center: Hall C

About GRANITE
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). Gritstone identifies these TSNA using its proprietary artificial intelligence platform, EDGE. GRANITE is an individualized neoantigen-based immunotherapy program that uses adenoviral ("prime") and self-amplifying mRNA ("boost") vectors 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.