Gritstone bio, Inc. presented positive safety, immunogenicity, and early efficacy data from its SLATE program, an off-the-shelf vaccine program targeting shared neoantigens, in combination with immune checkpoint blockade, for patients with advanced solid tumors at the 2022 European Society for Medical Oncology (ESMO) Congress. The presentation included initial data with SLATE-KRAS, a shared mutant KRAS-specific neoantigen vaccine candidate, in addition to updated data using the first version of the vaccine candidate (SLATE v1), which contains both KRAS and non-KRAS neoantigens. The data were presented by Chrisann Kyi, MD of Memorial Sloan Kettering Cancer Center during a mini-oral presentation on Saturday, September 10, 2022.

This Phase 1/2 study (NCT03953235) is evaluating the safety, immunogenicity, and early clinical activity of both SLATE v1 and SLATE-KRAS in combination with PD-1 checkpoint inhibitor Opdivo® (nivolumab) and subcutaneous anti-CTLA-4 antibody Yervoy® (ipilimumab) in patients with metastatic solid tumors harboring select KRAS mutations. SLATE v1 targets 20 shared neoantigens from KRAS, TP53, ß-catenin, and BRAF genes, while SLATE-KRAS is optimized to exclusively target KRAS neoantigens including the highly prevalent G12C, G12D, G12V and Q61H driver mutations. Gritstone developed the KRAS-optimized candidate (SLATE-KRAS) after initial testing of SLATE v1 suggested non-KRAS neoantigens (including TP53) might exhibit immunodominance over KRASmut, thus attenuating efficacy.

A total of 38 patients with advanced solid tumors have been enrolled in the study across cohorts using SLATE v1 (n=26) or SLATE-KRAS (n=12). The majority of patients enrolled (31/38) had either advanced non-small cell lung cancer (NSCLC; n=18) or microsatellite stable colorectal cancer (MSS-CRC; n=13). In the Phase 1/2 study, both SLATE-KRAS and SLATE v1 vaccine-based immunotherapies demonstrated: A favorable safety and tolerability profile Majority of treatment-related adverse events were Grade 1/2, with three = Grade 3 events reported with SLATE v1 and no = Grade 3 events reported with SLATE-KRAS Consistent and potent immunogenicity Induction of KRAS-specific CD8+ T cells: 55% of patients treated with SLATE-KRAS versus 31% of patients treated with v1 (by ex vivo ELISpot assay) Early objective evidence of efficacy as measured by reduction in ctDNA (molecular response) 39% (7/18) molecular response rate in evaluable patients with MSS-CRC and NSCLC.

Evaluable subjects had detectable KRASmut ctDNA at baseline and a post-baseline sample. All patients with NSCLC had progressed on prior (chemo)immunotherapy. In 18 patients with NSCLC, a molecular response was correlated with extended OS.

NSCLC patients with a molecular response demonstrated a median OS (9.6 months) more than double those without (4.5 months). The OS analysis included patients with no detectable ctDNA or no data at baseline (n=7) in the no molecular response group. At the time of data cut-off, there were insufficient evaluable patients in the CRC patient set to support a similar analysis.

Additionally, treatment with SLATE-KRAS induced a molecular response (normalization of tumor markers and reduction in ctDNA) and clinical benefit were observed in a patient with Stage IV KRAS G12V mutant MSS-CRC and multiple liver metastases who had progressed on two prior therapies.