On September 17, 2021 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company developing next generation cancer and infectious disease immunotherapies, reported results with its SLATE v1 product ("off-the-shelf" shared neoantigen immunotherapy in combination with intravenous nivolumab and subcutaneous ipilimumab) and dosing of the first patient in a Phase 2 clinical trial of the optimized SLATE v2 product (Press release, Gritstone Oncology, SEP 17, 2021, View Source [SID1234592015]). SLATE v2 has been engineered, based on human translational immunology data from v1 patients, to drive a more potent immune response to mutant KRAS neoantigens than were observed with SLATE v1. The data from SLATE v1 will be reviewed during the company’s previously announced investor event taking place today at 1:30pm ET.

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The v1 format of the SLATE immunotherapy was studied in a Phase 1/2 study, in collaboration with Bristol-Myers Squibb, in 26 patients with metastatic solid tumors, largely focused on non-small cell lung cancer (NSCLC), microsatellite-stable colorectal cancer (MSS-CRC) and pancreatic ductal adenocarcinoma (PDAC). There were no safety signals of note with the most common adverse events being low grade, self-limiting fever and injection site reactions. SLATE v1 exhibited evidence of efficacy in patients with NSCLC who had all progressed on prior anti-PD-(L)1 therapy (often in combination with chemotherapy) – with molecular responses (>50% decrease in ctDNA levels in the blood from baseline) observed in 3/5 NSCLC patients who were eligible for analysis.

SLATE v1 demonstrated the greatest activity in 6 NSCLC patients with the KRASmut G12C presented by the HLA protein A*02:01. Among these patients, ctDNA responses were observed in 66% of these patients (2/3 eligible for analysis), correlating with clinical benefit, and a RECIST radiologic response (unconfirmed) was observed in one 2nd line patient who had progressed after 3 months of 1st line chemo-immunotherapy. One patient who had progressed on prior chemo-immunotherapy after 8 months of treatment is nearing completion of 2 years of therapy with persistent ~20% tumor lesion shrinkage. The patient’s ctDNA was undetectable throughout the study.

A next generation, optimized SLATE cassette (v2), which exclusively includes epitopes from mutated KRAS and exhibited immunogenic superiority over v1 in human HLA-transgenic mice, is now in Phase 2 testing in patients with advanced NSCLC and CRC.

"We are excited to dose the first patient with the KRAS-specific version (v2) of our SLATE immunotherapy," said Andrew Allen, M.D., Ph.D., co-founder, president and chief executive officer of Gritstone. "We are very encouraged by the clinical data generated with v1, and product redesign using translational immunology data has enabled this optimized v2, which we are initially evaluating in more non-small cell lung cancer patients following progression on immunotherapy, as well as patients with microsatellite-stable colorectal cancer. We expect that these treatment settings will enable us to demonstrate the differentiated therapeutic potential of SLATE v2, and we anticipate having initial data by mid-2022. We look forward to presenting the data from SLATE v1 and from our individualized GRANITE program during our investor event in conjunction with ESMO (Free ESMO Whitepaper) 2021 later this week."

The SLATE v2 Phase 2 portion of the study is expected to enroll up to 60 patients with KRAS mutant-driven tumors in total across three cohorts: NSCLC post chemo-immunotherapy, first line MSS-CRC and third-line MSS-CRC. All patients will receive SLATE v2, consisting of a dose of intramuscular adenovirus-based prime with intramuscular self-amplifying mRNA-based boost vaccinations, in combination with PD-1 checkpoint inhibitor Opdivo (nivolumab) and subcutaneous anti-CTLA-4 antibody Yervoy (ipilimumab).
Opdivo and Yervoy are trademarks of Bristol-Myers Squibb Company.

About SLATE

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, or TSNA, that are identified by the company using its proprietary Gritstone EDGETM artificial intelligence platform and tumor HLA peptide sequencing. Gritstone’s SLATE "off-the-shelf" immunotherapy uses a priming adenoviral vector (GRT-C903) and self-amplifying mRNA vector (GRT-R904) to deliver a cassette of shared TSNA, representing mutated gene sequences that are found in multiple patients (such as KRAS mutations). SLATE is being evaluated in combination with immune checkpoint blockade in the Phase 2 portion of its clinical study (NCT03953235).