Transgene has achieved a significant milestone in personalized cancer immunotherapy by enrolling the first patient in the Phase II portion of its randomized Phase I/II clinical trial evaluating TG4050, an individualized therapeutic cancer vaccine for head and neck cancer. The French biotechnology company announced on June 3, 2024, that patient screening and enrollment are now active for the international multicenter trial, which aims to recruit approximately 80 patients overall.
Promising Phase I Results Drive Phase II Advancement
The decision to advance TG4050 to Phase II was based on compelling Phase I data presented at AACR 2024. The results demonstrated strong immunogenicity and persistent cellular immune responses, with notable clinical benefits for patients. At the time of analysis, all patients who received TG4050 remained disease-free, while only patients in the control arm had experienced relapse.
"The Phase I data we have generated indicate that TG4050 enables the induction of specific cellular immune responses that persist up to 7 months post treatment initiation, with all treated patients remaining disease-free after a median follow-up of 18.6 months," said Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene.
In the Phase I portion, 32 evaluable patients were included across France, the UK, and the USA. Almost all treated patients (95%) developed specific cellular immune responses (CD8+ and CD4+), and these immune responses were persistent and induced against multiple targets.
AI-Powered Personalized Immunotherapy
TG4050 is built on Transgene's myvac® viral vector platform combined with NEC's artificial intelligence capabilities for identifying and predicting the most immunogenic neoantigens for each patient. This virus-based therapeutic vaccine integrates approximately thirty tumor neoantigens, identified and selected from tumor sequencing to generate the most effective immune response.
The individualized treatment is created for each patient after they complete surgery and adjuvant therapy. The randomized study design evaluates treatment benefits in patients at high-risk of relapse, with half of participants receiving their vaccine immediately after completing adjuvant treatment and the other half receiving TG4050 at the time of disease recurrence as an additional treatment to standard of care.
Addressing Unmet Medical Need
The Phase II trial continues investigating single-agent TG4050 in patients with newly diagnosed, locoregionally advanced, HPV-negative, squamous cell carcinoma of the head and neck (SCCHN) in the adjuvant setting following completion of surgery and chemoradiotherapy. Despite some treatment advances, significant medical need remains for these patients.
With current standard of care, 30% to 40% of patients are expected to relapse within 24 months following surgery and adjuvant therapy. Despite completed Phase III trials, immune checkpoint inhibitors have yet to demonstrate significant benefits for these patients in the adjuvant setting.
TG4050 represents the only individualized neoantigen cancer vaccine currently being developed in a randomized trial for adjuvant treatment of head and neck cancer.
Trial Design and Timeline
The international, multicenter, open-label, two-arm trial (NCT04183166) is currently screening patients in France at IUCT-Oncopole (Toulouse) and Institut Curie (Paris), with additional sites in France, Europe, and the US to be added in coming months. The trial is led by Prof. Christian Ottensmeier, MD, PhD, Consultant Medical Oncologist at the Clatterbridge Cancer Centre and Professor of Immuno-Oncology at the University of Liverpool.
Trial endpoints include safety, feasibility, biological activity of the therapeutic vaccine, and disease-free survival (survival without recurrence or death for any cause). The inclusion of the last patient in the Phase II part of the study is expected in Q4 2025.
"Personalized cancer vaccines are an extremely exciting development and, if successful, could also be utilized to treat other forms of cancer to improve and extend the lives of patients," noted Dr. Brandely.
