Transgene's TG4050 Achieves 100% Two-Year Disease-Free Survival in Head and Neck Cancer Phase I Trial
核心洞察
Transgene's individualized neoantigen vaccine TG4050 demonstrated 100% two-year disease-free survival when used as adjuvant monotherapy in patients with high-risk, resected HPV-negative head and neck squamous cell carcinoma.
The Phase I trial showed TG4050 induced neoantigen-specific T cell responses in 73% of evaluable patients, with durable cytotoxic and effector responses lasting up to one year after treatment completion.
The comprehensive clinical and translational data from the randomized Phase I/II trial have been published as a preprint on medRxiv, supporting TG4050's potential to prevent cancer relapse through personalized immunotherapy.
Transgene has published comprehensive Phase I data demonstrating that its individualized neoantigen therapeutic vaccine TG4050 achieved 100% two-year disease-free survival as adjuvant monotherapy in patients with high-risk, resected, locally advanced HPV-negative head and neck squamous cell carcinoma (HNSCC). The French biotechnology company announced the preprint publication on medRxiv of both clinical and translational data from the Phase I portion of its randomized Phase I/II trial.
Addressing Critical Unmet Need in Head and Neck Cancer
Despite current treatment options including immune checkpoint inhibitors, approximately one-third of patients with HNSCC experience recurrence within two years following surgery. Transgene designed the TG4050 trial to evaluate whether inducing neoantigen-specific T-cell responses through an individualized neoantigen therapeutic vaccine (INTV) could reduce relapse risk.
The trial employed a randomized design where half of participants received TG4050 immediately after completing primary adjuvant treatment, while the other half received the vaccine at disease recurrence as additional therapy alongside standard of care. TG4050 encodes up to 30 predicted tumor neoantigens delivered via a Modified Ankara Virus (MVA) vector.
Robust Immune Response and Clinical Efficacy
The translational data revealed that TG4050 induced neoantigen-specific T cell responses in 73% of 15 evaluable patients. These immune responses demonstrated durability, with cytotoxic and effector phenotype markers expressed up to one year after treatment completion. The vaccine elicited strong polyepitopic, polyclonal, durable cytotoxic and effector neoantigen-specific CD8 T cell responses.
"The findings show encouraging evidence of TG4050's ability to induce durable, neoantigen-specific immune responses and its potential in preventing relapse in patients with HPV-negative operable head and neck cancer," said Katell Bidet-Huang, Head of translational medicine at Transgene.
Safety Profile and Manufacturing Platform
TG4050 demonstrated a favorable safety profile with no unexpected safety signals observed during the Phase I portion of the trial. The vaccine is based on Transgene's myvac® platform, which represents the company's entry into precision medicine with fully individualized immunotherapy tailored to each patient.
The myvac® approach utilizes artificial intelligence capabilities provided by partner NEC (搜索) to identify and select patient-specific mutations. NEC's Neoantigen Prediction System, based on more than two decades of AI expertise and trained on proprietary data, accurately prioritizes and selects the most immunogenic sequences for inclusion in each personalized vaccine.
Clinical Development Program
The Phase I portion included thirty-two evaluable patients in the ongoing randomized Phase I/II clinical trial (NCT04183166) for patients with HPV-negative head and neck cancers. An individualized treatment is created for each patient after surgery completion during adjuvant therapy.
First immunogenicity data from the Phase II portion are expected in the second half of 2026, with efficacy data becoming available once all patients reach two-year follow-up from randomization, unless events such as relapse, death, or loss to follow-up occur earlier.
The comprehensive data were initially presented at the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting and support TG4050's mechanism of inducing neoantigen-specific cytotoxic CD8+ T cell responses capable of targeting and eliminating tumor cells to prevent cancer relapse.
TG4050 represents the first myvac®-derived product in clinical evaluation, with the platform designed to stimulate patients' immune systems to recognize and destroy tumors using cancer-specific genetic mutations. The individualized immunotherapy is developed and manufactured specifically for each patient, marking a significant advancement in personalized cancer treatment approaches.