Phase I Trial of Neoantigen Vaccine Shows 100% DFS Rate in HNSCC

Findings from a phase I trial (NCT04183166) evaluating TG4050, a neoantigen therapeutic vaccine, in patients with operable, human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC) demonstrated a 100% disease-free survival (DFS) rate at 2 years, according to a press release from the manufacturer Transgene.¹

The study was designed to determine whether a vaccine tailored to each patient’s unique tumor mutations could train their immune system to attack remaining cancer cells. In the trial of 80 patients, half received TG4050 immediately after completing their initial postsurgery treatment. The other half received the vaccine only upon disease recurrence, in addition to standard care. All patients in the group treated immediately with TG4050 as a monotherapy remained disease free for the full 2-year follow-up period.

Primary end points were safety, tolerability, and DFS. Secondary end points were DFS and tumor response.

Supporting the clinical outcome, detailed translational data confirmed that the vaccine successfully activated the intended immune response. In 73% of evaluable patients, TG4050 induced T-cell responses specific to the neoantigens targeted by the vaccine. In addition, TG4050 was well tolerated and showed no unexpected safety signals.

These responses proved durable, with cytotoxic and effector phenotype markers expressed up to 1 year after the end of treatment.

Previous Presentation

An overview of these immunogenicity data was initially presented at the 2025 Society for Immunotherapy of Cancer Annual Meeting.² At that time, investigators reported that vaccine-induced CD8+ T cells demonstrated an effector phenotype 1 year after treatment ended, suggesting potential long-term effector functions.

Additionally, they noted the presence of high levels of cytotoxic and tissue-resident biomarkers, suggesting that these cells are effective at killing cancer cells and likely to be found not only in the blood but also in tissues, where they can scout for and eliminate tumor cells.

What Is TG4050?

TG4050 is an individualized neoantigen therapeutic vaccine (INTV) that encodes up to 30 patient-specific tumor markers, delivered via a Modified Vaccinia Ankara (MVA) viral vector. Despite standard treatments, including surgery and immunotherapy, approximately one-third of these patients typically see their cancer return within 2 years.

“The findings show encouraging evidence of TG4050’s ability to induce durable, neoantigen-specific immune responses and its potential in preventing relapse,” said Katell Bidet-Huang, Head of Translational Medicine at Transgene, in the release.¹

The preprint of the current trial, titled, “Viral-Based Individualized Neoantigen Vaccine As Adjuvant Treatment In Resected Head And Neck Squamous Cell Carcinoma: Immunogenicity And Efficacy From A Randomized Phase I Trial,” is available on medRxiv and Transgene’s website while undergoing formal peer review for journal publication.

REFERENCES

1. Transgene published phase I data supporting TG4050’s potential in preventing head and neck cancer relapse. News release. Transgene. January 9, 2025. Accessed January 12, 2025. https://tinyurl.com/7zyw5u2n

2. New phase I immunological data presented at SITC 2025 support TG4050’s potential role in preventing cancer relapse. News release. Transgene. November 4, 2025. Accessed January 12, 2025. https://tinyurl.com/2kcew59b