TG4050 for Head and Neck Cancer

Not currently recruiting at 16 trial locations

Overseen By Transgene EU, Clinical Operations Department

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Transgene

Must not be taking: Anti-cancer vaccines, Anti-PD1

Disqualifiers: HIV/AIDS, Hepatitis B/C, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TG4050 for individuals with squamous cell carcinoma of the head and neck, a cancer affecting areas like the mouth and throat. The study aims to assess the treatment's safety and effectiveness. Participants will be divided into two groups: one will start TG4050 after their primary treatment, and the other will begin at cancer recurrence. Suitable candidates have been newly diagnosed with advanced head and neck cancer, have completed their initial treatment, and show a complete response (no signs of cancer after treatment). As a Phase 1, Phase 2 trial, this research focuses on understanding how TG4050 works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on another investigational agent, you may need to stop that treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TG4050, a new treatment being tested for head and neck cancer, is safe and generally well-tolerated by patients. Studies indicate that TG4050 can enhance the immune system without causing serious side effects. Early results confirm that this personalized cancer vaccine is safe, even in challenging cases where the cancer is difficult for the immune system to target. In one study, none of the patients who received TG4050 experienced a recurrence of their cancer, suggesting it might be both safe and effective. Overall, TG4050 appears promising for patients with head and neck cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for head and neck cancer?

Researchers are excited about TG4050 for head and neck cancer because it represents a personalized approach to treatment. Unlike traditional therapies like surgery, radiation, and chemotherapy, TG4050 uses a patient's unique tumor mutations to create a custom vaccine. This vaccine trains the immune system to specifically target and attack cancer cells, potentially improving precision and effectiveness. By focusing on individual tumor characteristics, TG4050 aims to enhance treatment outcomes and reduce side effects commonly associated with conventional cancer treatments.

What evidence suggests that TG4050 might be an effective treatment for head and neck cancer?

Research has shown that TG4050 may effectively treat head and neck cancer. In this trial, participants in Arm A will begin TG4050 treatment after completing their primary treatment. Previous studies have shown that all patients who started TG4050 after their main treatment remained cancer-free for 28.5 months. Meanwhile, participants in Arm B will start TG4050 treatment at the time of recurrence. In another study group, three patients experienced a relapse. The treatment was generally well-tolerated, with only mild to moderate side effects. These findings suggest that TG4050 might help prevent cancer recurrence, especially when started early, and provide hope for its effectiveness in managing this type of cancer. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

Adults with newly diagnosed stage III or IVA squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx who are in complete response after primary tumor treatment. Participants must be generally healthy with an ECOG performance status of 0 or 1 and have proper organ function. Excluded are those with other active cancers, prior cancer immunotherapies, HIV/AIDS, hepatitis infections, pregnant/nursing women, and recent involvement in other drug trials.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My blood, liver, and kidney functions are all within normal ranges.

I have been newly diagnosed with advanced cancer in my mouth or throat.

Exclusion Criteria

I do not have any uncontrolled illnesses.

I have previously received immunotherapy for cancer.

My cancer is not from the skin, salivary gland, or sinuses and is not squamous cell carcinoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TG4050 treatment either at completion of primary treatment or at the time of recurrence

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• TG4050

Trial Overview The trial is testing TG4050's safety and potential effectiveness for head and neck cancer patients. It's a phase I study where participants are randomly assigned to one of two groups to receive this experimental vaccine therapy. The study is open-label meaning both researchers and participants know what treatment is being given.

How Is the Trial Designed?

Group I: Arm B: Study treatment initiation at recurrence Experimental Treatment 1 Intervention

TG4050 treatment initiation at the time of recurrence

Group II: Arm A : Early study treatment initiation Experimental Treatment 1 Intervention

TG4050 treatment initiation at completion of primary treatment

Who Is Running the Clinical Trial?

Transgene

Lead Sponsor

Trials

23

Recruited

1,700+

Published Research Related to This Trial

In a Phase III study involving 219 Chinese patients with advanced squamous cell carcinoma of the head and neck, the combination of dose-modified docetaxel, cisplatin, and 5-fluorouracil (TPF) showed a higher overall response rate (76.3%) compared to the PF regimen (52.9%), indicating increased anti-tumor activity.

However, the addition of docetaxel did not significantly improve progression-free survival (PFS), with median PFS being 400 days for TPF and 342 days for PF, suggesting that while TPF may enhance response rates, it does not extend the time before disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant dose-modified docetaxel in squamous cell carcinoma of the head and neck: A phase 3 study. Sun, Y., Guo, W., Bai, Y., et al.[2020]

The TPFL regimen (docetaxel, cisplatin, fluorouracil, and leucovorin) demonstrated a 47.6% overall clinical response rate in 21 patients with advanced squamous cell carcinoma of the head and neck, indicating its potential efficacy in treating this condition.

The treatment was associated with manageable toxicities, primarily mucositis, fatigue, and anorexia, suggesting that TPFL has an acceptable safety profile for patients who are not candidates for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxotere, cisplatin, fluorouracil, and leucovorin (TPFL)as induction chemotherapy for locally advanced squamous cell carcinoma of the head and neck. Kamnerdsupaphon, P., Chitapanarux, I., Lorvidhaya, V., et al.[2018]

Cisplatin combined with 5-fluorouracil (5-FU) remains the standard treatment for head and neck cancer (HNC), but new strategies are being explored to enhance its effectiveness, including using oral fluoropyrimidines and alternative cisplatin formulations.

Cetuximab, an anti-EGFR monoclonal antibody, has shown a consistent response rate of 10-13% in patients with platinum-refractory recurrent or metastatic HNC, and a recent Phase III trial indicated that combining cetuximab with cisplatin improves response rates compared to cisplatin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in head and neck cancer therapy: the role of new cytotoxic and molecular-targeted agents. Caponigro, F., Milano, A., Basile, M., et al.[2018]

The FDA has approved the first immunotherapies, nivolumab and pembrolizumab, for treating recurrent squamous cell carcinoma of the head and neck (HNSCC), marking a significant advancement in treatment options for patients who have not responded to traditional platinum-based chemotherapy.

These approvals represent the first new therapies for HNSCC since 2006 and include guidelines for patient selection and management, aiming to improve outcomes and standardize the use of immunotherapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). Cohen, EEW., Bell, RB., Bifulco, CB., et al.[2023]

Cytotoxic chemotherapy for recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC) primarily includes platinum agents, taxanes, and antimetabolic agents, which are commonly used to manage the disease.

Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, shows modest effectiveness in treating R/M HNSCC, highlighting the importance of a multidisciplinary approach in palliative care planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current recommendations for systemic therapy of recurrent and/or metastatic head and neck squamous cell cancer. Fury, MG., Pfister, DG.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6016

Randomized phase I trial of adjuvant personalized cancer ... After a median follow-up of 28.5 months, all 16 pts receiving TG4050 in Arm A remained disease-free whereas 3 out of 16 pts in Arm B relapsed.

2. asco.org asco.org/abstracts-presentations/ABSTRACT495236

Randomized phase I trial of adjuvant personalized cancer ... The multicenter, open label, randomized, 2-arm Phase I trial evaluated TG4050 in LA HNSCC pts achieving complete remission following surgery and adjuvant ...

3. transgene.fr transgene.fr/CP.php?f=35215&link=20250916_Transgene_2025_Half-Year-Results_EN.pdf

Randomization to be Completed in Phase II Part in Q4 2025 Positive Phase I data with TG4050 in operable Head and Neck. Squamous Cell Carcinoma (HNSCC). • 100% disease-free survival after 2 years of ...

4. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A746

650 Randomized phase I trial of adjuvant individualized ... All TG4050-related adverse events were mild to moderate. Disease-free survival data after a median follow-up of 24 months will be presented.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04183166

A Clinical Trial Evaluating TG4050 in Head and Neck Cancer Study Overview. This is a multicenter, open-label, two arms, randomized, phase I/II study evaluating the safety and tolerability as well as some activity ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.6082

A personalized cancer vaccine in head and neck carcinoma. Our preliminary data demonstrate that TG4050 is safe, well tolerated, and capable of inducing T cell responses in cold tumors.

7. transgene.fr transgene.fr/wp-content/uploads/20250601_PR_ASCO_TG4050_EN.pdf

20250601_PR_ASCO_TG4050_... These positive data confirm that individualized neoantigen therapeutic vaccine TG4050 is safe and feasible in the adjuvant setting of resectable ...