Multicenter randomized phase 1 trial of adjuvant viral-based individualized neoantigen vaccine in head and neck squamous cell carcinoma

In approximately one third of patients, resected head and neck squamous cell carcinoma (HNSCC) will recur. A multicenter randomized phase 1 trial investigated whether induction of tumor neoantigen-specific T cell responses could prevent relapse in these patients. An individualized neoantigen therapeutic vaccine (TG4050) encoding up to 30 patient-specific tumor neoantigens delivered by a modified Vaccinia Ankara viral vector was tested as a single agent immediately after standard of care adjuvant therapy compared with watchful waiting. The primary endpoint was safety, secondary endpoints included feasibility and efficacy, and immunogenicity was exploratory. TG4050 was well tolerated. Of 16 evaluable patients randomized in the immediate treatment arm, non relapsed during a median follow-up of 30 months, while 3 of 16 relapsed in the control arm. T cell responses to vaccine neoantigens were detected in 73.3% of patients treated with TG4050, with a median of 3 neoantigens per responder. These responses were maintained throughout treatment and persisted for over one year after the last dose. Vaccine neoantigen-specific CD8⁺ T cells had an effector phenotype, displayed high expression of cytotoxic and tissue-resident markers, were polyclonal and comprised both de novo responses and amplification of pre-existing tumor-infiltrating T cell clones. The authors conclude that these data are consistent with the hypothesis that single-agent delivery of TG4050 can prevent tumor recurrence after resection of HNSCC.