Transgene and NEC Corporation have reported sustained 100% three-year disease-free survival (DFS) among patients treated with the individualized neoantigen therapeutic vaccine TG4050 in the Phase 1 portion of a randomized Phase 1/2 trial in resected, locally advanced HPV-negative head and neck squamous cell carcinoma (HNSCC).
The companies also announced that comprehensive Phase 1 clinical and translational findings from the study have been published in Nature Communications, providing peer-reviewed evidence of durable, patient-specific immune responses generated by the investigational vaccine.
All TG4050-Treated Patients Remain Disease-Free at Three Years
With a median follow-up of 41 months, all 16 patients who received TG4050 remained disease-free, while 3 of 16 patients in the control arm experienced disease recurrence.
TG4050, which can encode up to 30 patient-specific neoantigens, also continued to demonstrate a favorable safety profile, with no unexpected safety findings reported.
Alessandro Riva, MD, Chairman and Chief Executive Officer of Transgene, described the long-term findings and peer-reviewed publication as an important milestone for the program.
“Persistent neoantigen-specific immune responses support TG4050’s potential to generate durable anti-tumor immunity in patients with head and neck cancer at high risk of relapse.”
The results come from the Phase 1 portion of NCT04183166, a randomized Phase 1/2 study evaluating TG4050 in patients with resected HPV-negative head and neck cancer who remain at risk of relapse following surgery and adjuvant treatment.
While the findings are encouraging, they come from a small Phase 1 population, and TG4050 remains an investigational treatment. The ongoing Phase 2 portion of the trial is designed to further evaluate its efficacy.
Phase 1 Results Published in Nature Communications
The peer-reviewed Phase 1 data published in Nature Communications include detailed clinical and translational analyses of the immune responses induced by TG4050.
Vaccine-induced neoantigen-specific T-cell responses were detected in 73.3% of patients treated with TG4050, with a median of three responding neoantigens per responder.
The responses were maintained throughout treatment and persisted for more than one year after the final vaccination, providing evidence of durable anti-tumor immunity.
Christian Ottensmeier, MD, PhD, FRCP, of the University of Liverpool and La Jolla Institute for Immunology, and Principal Investigator of the study, said:
“Robust and persistent CD8+ T-cell responses against patient-specific tumor neoantigens were observed following TG4050 vaccination, supporting the vaccine’s ability to generate a targeted anti-tumor immune response.”
He added that the findings further support the potential of TG4050 as an individualized immunotherapy for patients with head and neck cancer at risk of recurrence.
How Does TG4050 Work?
TG4050 is an individualized cancer immunotherapy developed using Transgene’s myvac platform and NEC’s artificial intelligence and machine-learning technologies.
For each patient, tumor-specific mutations are identified and analyzed using NEC’s Neoantigen Prediction System. Up to 30 selected neoantigens can then be encoded into a Modified Vaccinia Ankara viral vector to create a vaccine tailored to the individual patient.
The aim is to stimulate T cells capable of recognizing and attacking cancer cells carrying those patient-specific neoantigens.
Masaki Kondo, Corporate Executive and Managing Director of NEC Corporation’s Life Science Division, said the results reinforce the potential of individualized neoantigen-based immunotherapy.
“These results additionally demonstrate that NEC’s AI-powered neoantigen prediction can identify highly relevant tumor targets capable of generating clinically meaningful immune responses.”
Kondo added that NEC remains committed to its collaboration with Transgene and to advancing technologies designed to bring individualized cancer treatments to patients.
Could Personalized Vaccination Help Prevent Head and Neck Cancer Recurrence?
Patients with locally advanced head and neck squamous cell carcinoma can remain at substantial risk of recurrence even after surgery and adjuvant radiotherapy or chemoradiotherapy.
TG4050 is being investigated as an adjuvant immunotherapy intended to generate immune responses against residual tumor cells before clinical recurrence develops.
The sustained disease-free outcomes observed to date, together with persistent neoantigen-specific CD8+ T-cell responses, provide further rationale for testing the approach in a larger randomized population.
Phase 2 Evaluation of TG4050 Continues
TG4050 continues to be evaluated in the randomized Phase 1/2 trial NCT04183166 in patients with resected head and neck squamous cell carcinoma.
According to Transgene and NEC, the next planned milestones include initial immunological data from the Phase 2 portion of the study in the second half of 2026, followed by two-year disease-free survival data in the first quarter of 2028.
The larger Phase 2 dataset will be important for determining whether the encouraging recurrence-free outcomes observed in the initial Phase 1 cohort can be confirmed in a broader patient population.
If validated, the approach could strengthen the case for individualized neoantigen vaccines as an adjuvant strategy aimed at reducing recurrence risk in patients with high-risk head and neck cancer.
Read further on OncoDaily: Merck and Moderna’s Intismeran Autogene Plus Keytruda Meets Phase 3 RFS and DMFS Endpoints in Resected Melanoma
