Lynch Syndrome Neoantigen Vaccine is Well-Tolerated, Demonstrates Immunogenicity

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Microsatellite instability (MSI) tumors are frequently found in people with Lynch syndrome, one of the most common hereditary colorectal cancers.

Eduardo Vilar-Sanchez, MD, PhD

Eduardo Vilar-Sanchez, MD, PhD

Nouscom's Nous-209 genetic neoantigen vaccine was well-tolerated and elicited immune responses in people with Lynch syndrome (LS), according to initial data from a phase 1b/2 trial (NCT05078866).1

Data from the trial were presented at The Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting, held November 1-5 in San Diego, California, by Anna Morena D'Alise, PhD, vice president, immunology, Nouscom.1

“Microsatellite instability (MSI) tumors are characterized by defects in the DNA mismatch repair (MMR) genes that lead to the accumulation of mutations within microsatellite (MS) loci. Indels in MS regions of coding genes can result in the synthesis of shared frameshift neoantigens, expected to be immunogenic and safe. MSI tumors develop sporadically or secondary to hereditary predisposition as part of LS, one of the most common hereditary colorectal cancers,” D-Alise and colleagues wrote.1

The data reported are from the first 10 patients with LS treated in the single-arm, open-label clinical trial. The trial is primarily evaluating safety and immunogenicity of Nous-209, administered intramuscularly with 1 prime with a Great Ape Adenovirus (GAd20-209-FSPs) on day 1 and a boost with a Modified Vaccinia Ankara (MVA-209-FSPs) at week 8. Biomarker assays were conducted on blood samples collected at baseline, weeks 3, 8, 9, 24, and 52. Immunogenicity is evaluated on peripheral blood mononuclear cells (PBMCs) before and after vaccination by ex vivo IFNγ ELISpot assay.1

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“The work of the Cancer Prevention Clinical Trials Network is to support early trials that may give LS patients a new way to intercept cancer and possibly lower their cancer risk over time. The presented data suggest that a novel vaccine such as NOUS-209 could provide a compelling approach for cancer interception in LS carriers,” principal investigator Eduardo Vilar-Sanchez, MD, PhD, Professor, Clinical Cancer Prevention, MD Anderson, said in astatement.2

Of the 10 participants, 4 (40%) were less than 50 years of age and 6 (60%) were at least 50 years of age. Most were male (90%) and most were white (90%). Two (20%) were positive for the MLH1 gene, 4 (40%) were positive for MSH2 (40%), and 4 for PMS2 (40%). There were no treatment-related serious adverse events (AEs) and the vaccine was generally well-tolerated, with mostly grade 1 and 2 AEs after both parts of the vaccination.

“These first data demonstrate that NOUS-209 monotherapy can potently and broadly stimulate the immune system in LS subjects, so as tobe ready to intercept the development of MSI tumors at an early stage. We are deeply indebted to all ourcollaborators at the NCI and LS trial volunteers, who collectively are highly motivated in our goal to intercept cancer,” Elisa Scarselli, MD, chief scientific officer, Nouscom, added to the statement.2

The investigators found that Nous-209 elicited a robust and broad immune response in all participants, as measured by testing T-cell reactivity with ex vivo IFNγ ELISpot assay against 16 peptide pools covering the vaccine sequence compared to baseline.1 The therapy subsequently induced CD8 and CD4 T-cell responses. Nous-209 was previously evaluated in a phase 1/2 trial (NCT04041310) in combination with pembrolizumab which showed similar supporting safety and efficacy data. The current phase 1b trial plans to enroll up to 45 participants with LS across the US by early 2024.2

“These data are a testament to the power of a true collaboration between industry and academia in our shared ambition to intercept cancer before it can take hold for the huge numbers of LS carriers. We look forward to reporting the full Phase 1b results and outlining the next steps in initiating randomized Phase 2 trials next year,” Richard Davis, PhD, chief operating officer, Nouscom, added.2

Click here to read more coverage of the 2023 SITC meeting.

REFERENCES
1. D’Alise M, Willis J, Leoni G, et al. Nous-209 genetic vaccine encoding shared cancer neoantigens is safe and elicits robust immune response in healthy Lynch syndrome carriers: interim results from Phase 1 cancer interception trial. Presented at: SITC 38th Annual Meeting; November 1-5; San Diego, California. Abstract #LB1526
2. Nouscom’s off-the-shelf cancer vaccine, NOUS-209, shows potential to ‘intercept’ cancer in subjects with Lynch syndrome. News release. Nouscom. October 31, 2023. https://www.nouscom.com/2023/10/31/nouscoms-off-the-shelf-cancer-vaccine-nous-209-shows-potential-to-intercept-cancer-in-subjects-with-lynch-syndrome/#
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