Early Efficacy Signals: Transgene’s Personalized Vaccine Hits Two-Year Mark Without Relapse in Phase I Trial

French biotech firm Transgene has released preliminary 24-month data from its Phase I trial of TG4050, a personalized neoantigen vaccine targeting head and neck cancers. The data, recently shared via medRxiv, indicates that none of the patients in the small treatment arm experienced a recurrence during the two-year observation period. While the results are encouraging, researchers emphasize that these findings stem from a limited cohort of 16 patients, and the primary objective of the study was to establish safety and immunogenicity rather than definitive clinical efficacy.

Preliminary Data from a Narrow Cohort

The trial focused on patients with HPV-negative head and neck squamous cell carcinoma (HNSCC) who had undergone surgery and adjuvant chemoradiation. This specific patient population faces a high risk of recurrence; historically, roughly 30% of patients relapse within 24 months. In this randomized study, the 16 patients who received TG4050 remained disease-free at the two-year mark, while two relapses were recorded in the control group (N=17) receiving the current standard of care.

Despite the "perfect" survival figure in this small sample, oncologists caution against over-interpreting Phase I data. The small "N" means the trial lacks the statistical power to prove the vaccine is the sole driver of the survival trend. However, the data provides a necessary signal to proceed into larger Phase II trials, where the vaccine will be tested against the high recurrence rates that have long characterized HNSCC.

Engineering the Response: The MVA Vector vs. mRNA

TG4050 belongs to the class of Individualized Neoantigen Therapeutic Vaccines (INTV). Each dose is manufactured to target up to 30 patient-specific mutations identified through genomic sequencing.

While mRNA platforms from Moderna and BioNTech have dominated the headlines, Transgene utilizes a Modified Vaccinia Ankara (MVA) viral vector. The choice of MVA offers distinct technical advantages:

• Thermal Stability: Unlike mRNA vaccines that require ultra-cold storage, MVA-based therapies are more stable at higher temperatures, potentially simplifying the logistics of a global rollout.
• Immunogenic Profile: The MVA vector acts as its own adjuvant, triggering a robust innate immune response that helps recruit T-cells to the tumor site. This may lead to a more durable CD8+ "killer" T-cell response compared to lipid-nanoparticle-delivered mRNA.

The Competitive Landscape: Early-Stage Signals Across Indications

The results from Transgene are not isolated, but rather part of a broader shift toward personalized immunotherapy. Several other platforms have reported similar early-stage signals that suggest a departure from the traditional "wait and see" approach after surgery.

• Breast Cancer (FLAMINGO-01): Phase IIb data for this vaccine indicated strong disease-free survival estimates in HER2-positive patients, though long-term data for larger populations is still pending.
• Dostarlimab (MSK): In a small but highly publicized study at Memorial Sloan Kettering, immunotherapy alone led to complete remission in 100% of a specific subset of rectal cancer patients (MMRd), highlighting the power of targeting specific genetic signatures.
• Autogene Cevumeran: This mRNA-based pancreatic cancer vaccine has demonstrated that vaccine-induced T-cells can persist for years, though, like TG4050, it faces the challenge of proving these results in a broader, more diverse patient base.

Scaling the Bespoke Model

As the industry moves into 2026, the primary hurdle for TG4050 and its competitors is no longer just biological—it is industrial. Manufacturing a unique vaccine for every patient is a logistically intensive process that currently takes weeks, a timeframe that may be too long for patients with fast-progressing disease.

Transgene is currently optimizing its automated manufacturing platform to reduce turnaround times and costs. With several major regulatory filings for neoantigen vaccines expected across the industry later this year, the focus is shifting from small-scale clinical success to the feasibility of integrating these "bespoke" therapies into standard oncology workflows. The upcoming Phase II trials will be the true test of whether these early 100% survival signals can be replicated in the real-world population.