A Neoantigen Vaccine plus Anti–PD-1 Elicits Antitumor T-cell Responses

Mutations in tumor cells result in the presentation of neoantigens, which can be targeted by T cells, on tumor-cell surfaces. In an open-label, phase Ib trial, Ott and colleagues investigated the use of a personalized neoantigen vaccine (NEO-PV-01) plus PD-1 blockade with nivolumab in 60 patients with high–tumor mutational burden advanced melanoma (27 patients), non–small cell lung cancer (NSCLC; 18 patients), or urothelial carcinoma of the bladder (15 patients). The objective response rates for the vaccinated patients were 59%, 39%, and 27%, with median progression-free survival of 23.5 months, 8.5 months, and 5.8 months and one-year overall survival rates of 96%, 83%, and 67% for patients with melanoma, NSCLC, and bladder cancer, respectively. The most common treatment-emergent adverse events among vaccinated patients were injection-site reactions and influenza-like illness. An exploratory post hoc analysis suggested that progression-free survival in patients with melanoma might be linked to increased levels of effector memory T cells, higher T-cell receptor clonality, and greater numbers of TCF7⁺CD8⁺ T cells in the tumor microenvironment. In all patient cohorts, the combination treatment produced T-cell reactivity toward neoantigen epitopes that was durable and mutation-specific. The vaccine-induced neoantigen–specific T cells exhibited desirable characteristics, such as ability to navigate to metastatic tumors, cytotoxicity toward tumor cells, and induction of epitope spreading, a phenomenon that suggests in vivo tumor-cell killing by the vaccine-induced neoantigen-specific T cells leading to expansion of T-cell responses to additional tumor neoantigens. In summary, this trial provides evidence that the NEO-PV-01 vaccine in combination with nivolumab is safe, shows preliminary signs of efficacy, and elicits promising T-cell responses.

Ott PA, Hu-Lieskovan S, Chmielowski B, Govindan R, Naing A, Bhardwaj N, et al. A phase Ib trial of personalized neoantigen therapy plus anti-PD-1 in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. Cell 2020;183:347–62.E24.

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