Neoantigens derived from tumor-associated mutations can elicit T cell-mediated antitumor immunity and facilitate tumor rejection. Here, we assessed the safety and efficacy of personalized neoantigen peptide vaccination (PPV) in advanced NSCLC patients who had failed conventional therapy.
24 stage III/IV recurrent NSCLC patients were immunized with mixtures of short and long neoantigen peptides based on personalized tumor-associated mutations and predicted HLA peptide binding affinities. Primary study endpoints were feasibility and safety. Secondary endpoints were PPV-induced immune responses, progression-free survival (PFS) and overall survival (OS).
Aside from transient rash, fatigue and/or fever in 3 patients, no treatment-related adverse events were observed. The median PFS and OS of the 24 PPV patients was 6.0 and 8.9 months, respectively. Of the 16 PPV patients bearing EGFR mutations, 7 experienced objective tumor response by RECIST 1.1, including 6 PR and 1 CR. Of the 8 patients expressing wild-type EGFR, 4 showed SD and no PR or CR. Importantly, 9 PPV patients who continued EGFR inhibitor (EGFRi) therapy in spite of prior progression showed extended survival compared to 7 patients who stopped EGFRi prior to initiating PPV (median OS: 13.8 vs. 7.6 months, P = 0.038), though both patient groups experienced similar objective response rates. Immune monitoring demonstrated the immunogenicity of two highly shared EGFR mutations in multiple responding patients. Robust PPV-specific immune responses were observed in 4 responding patients, with ELISPOT and tetramer staining showing incremental increases in peripheral blood neoantigen-specific CD8+ T cell frequencies for up to 3 months during PPV. T-cell receptor (TCR) Vb sequencing also demonstrated significantly increased frequencies of neoantigen-specific CD8+ TCR clones in both peripheral blood and tumor-infiltrating lymphocytes following PPV.
These results suggest that PPV is safe and potentially beneficial for advanced stage EGFR-mutated NSCLC patients. Survival analyses imply that PPV in combination with EGFRi may be a viable treatment option for NSCLC, in spite of prior EGFRi failure.
ChiCTR-INR-16009867.
Tianjin Beichen Hospital.
Tianjin HengJia Biotechnology Development Co., Ltd.
F. Li: Shareholder / Stockholder / Stock options: Tianjin HengJia Biotechnology Development Co., Ltd. G. Lizee: Advisory / Consultancy: HengJia Neoantigen Biotechnology (Tianjin) Co., Ltd. P. Hwu: Advisory / Consultancy: Dragonfly Therapeutics; Advisory / Consultancy: GlaxoSmithKline; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Immatics; Advisory / Consultancy: Sanofi; Research grant / Funding (institution): Genentech. L. Deng: Full / Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd. Q. Zou: Full / Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd. M.A. Stairs: Advisory / Consultancy: HengJia Neoantigen Biotechnology (Tianjin) Co., Ltd. C. Chen: Full / Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd. C. Huo: Full / Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd. Y. Wang: Full / Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd. All other authors have declared no conflicts of interest.