2022 World Conference on Lung Cancer (ePosters)-EP08.01-086. Pooled Mutant KRAS-Targeted Peptide Vaccine with Nivolumab and Ipilimumab in Advanced KRAS Mutated Non-Small Cell Lung Cancer

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This document describes a phase I study conducted at the Sidney Kimmel Comprehensive Cancer Center to evaluate the safety and feasibility of a novel treatment approach for advanced non-small cell lung cancer (NSCLC) with KRAS mutations. The study aims to combine a pooled mutant-KRAS peptide vaccine with immune checkpoint inhibitors nivolumab and ipilimumab.<br /><br />The background of the study highlights the significant advancements in the treatment of NSCLC through immunotherapeutic and molecular-based therapies. The interplay between genomic alterations and response to immune checkpoint blockade is emphasized, especially in the context of KRAS mutations, which occur in approximately 30% of NSCLC cases.<br /><br />While there have been recent developments in the treatment of KRASG12c mutated cancers with small molecule inhibitors, the duration of disease control and activity across codon mutations remain limited. Therefore, there is a need for further development of KRAS-targeted therapy.<br /><br />The study proposes a targeted vaccine approach, which is attractive since KRAS is an oncogenic driver less likely to be immunologically edited. Previous preclinical and early clinical trial data have shown the benefits of combining targeted synthetic long peptide vaccines with immune checkpoint inhibitors and adjuvant stimulants in the treatment of solid malignancies.<br /><br />The study protocol involves the administration of the KRAS peptide vaccine in combination with nivolumab and ipilimumab in the first-line treatment setting for patients with unresectable KRAS-mutated NSCLC. Safety, feasibility, progression-free survival, KRAS mutant T-cell responses, T-cell transcriptomic profiling, and ctDNA dynamics are among the study endpoints.<br /><br />The inclusion criteria for the study specify that eligible participants must be adults with untreated unresectable KRAS mutant NSCLC, an ECOG performance status of 0-1, and measurable disease. Exclusion criteria include recent chemotherapy or radiation therapy, baseline steroid requirements, active autoimmune conditions, immunodeficiency, HIV, HBV/HCV infection, and prior organ transplant.<br /><br />In summary, this phase I study aims to evaluate the safety and feasibility of a novel treatment approach combining a KRAS peptide vaccine with immune checkpoint inhibitors for advanced KRAS-mutated NSCLC. The study intends to contribute to the development of targeted therapy options for this patient population.

Asset Subtitle

Samuel Rosner

Meta Tag

Speaker Samuel Rosner

Topic Metastatic Non-small Cell Lung Cancer - Immunotherapy

Keywords

phase I study

KRAS mutations

peptide vaccine

immune checkpoint inhibitors

NSCLC

targeted therapy

unresectable

safety

feasibility

genomic alterations