TG4050 (individualized MVA neoantigen vaccine) shows 0/16 per-protocol relapses at 30 months in resected HPV-negative HNSCC

TG4050 is a personalized therapeutic cancer vaccine delivered through a Modified Vaccinia Ankara (MVA) vector encoding up to 30 patient-specific predicted neoantigens to generate tumor-directed T-cell immunity. In this randomized Phase 1 adjuvant trial (NCT04183166), patients with resected, locally advanced HPV-negative HNSCC received standard postoperative therapy and were then assigned to immediate TG4050 or observation, with vaccination available to the observation group after recurrence. Among the per-protocol efficacy population, 0/16 patients receiving immediate TG4050 had relapsed at a median 30 months of follow-up versus 3/16 in the observation arm; importantly, 17 patients were originally randomized to immediate vaccination, and one developed an early recurrence after only two doses and was excluded from the per-protocol analysis because minimum treatment exposure was not met. TG4050 was generally well tolerated and induced vaccine-specific T-cell responses in 73.3% of immediately treated patients, with durable, polyclonal CD8+ responses persisting more than a year after the last dose.