Multiple studies indicate that cytotoxic CD8 T cells targeting tumor neoantigens are critical to tumor control and clearance in response to immunotherapies targeting CTLA-4 or PD-1 6, 7, 8, 9, 10. Although small study size limits statistical and translational analyses, the increased OS observed in MSS-CRC warrants further exploration in larger randomized studies.Ĭancer immunotherapies have shown promise in harnessing the immune system to target and destroy cancers, leading to clinical benefit enriched in patients with a high mutational burden 1, 2, 3, 4, 5. Exploratory biomarker analyses showed decreased circulating tumor DNA (ctDNA) in patients with prolonged OS. Several patients with microsatellite-stable colorectal cancer (MSS-CRC) had improved OS. Vaccine manufacturing was feasible, with vaccination inducing long-lasting neoantigen-specific CD8 T cell responses. Secondary endpoints included immunogenicity, feasibility of manufacturing and overall survival (OS). The RP2D was 10 12 viral particles (VP) ChAd68 and 30 µg samRNA. Serious TRAEs included one count each of pyrexia, duodenitis, increased transaminases and hyperthyroidism. Treatment-related adverse events (TRAEs) >10% included pyrexia, fatigue, musculoskeletal and injection site pain and diarrhea. The individualized vaccine regimen was safe and well tolerated, with no dose-limiting toxicities.
Safety, tolerability and recommended phase 2 dose (RP2D) of an individualized, heterologous chimpanzee adenovirus (ChAd68) and self-amplifying mRNA (samRNA)-based neoantigen vaccine in combination with nivolumab and ipilimumab were assessed as primary endpoints in an ongoing phase 1/2 study in patients with advanced metastatic solid tumors (NCT03639714).
T cell-inducing vaccines hold promise to exert long-lasting disease control in combination with CPI therapy. Nature Medicine volume 28, pages 1619–1629 ( 2022) Cite this articleĬheckpoint inhibitor (CPI) therapies provide limited benefit to patients with tumors of low immune reactivity.
Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results