TG4001 + Avelumab for Cancer

Not currently recruiting at 20 trial locations

Overseen By Transgene EU, Clinical Operations Department

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Transgene

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS metastases, Cardiovascular disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for advanced cancers linked to HPV-16, a type of virus. The study tests the effectiveness of combining TG4001 with avelumab, an immunotherapy drug, against these cancers. Some participants will receive both treatments, while others will receive only avelumab. This trial may suit those with advanced HPV-16 positive cancers, such as cervical or anal cancer, that cannot be treated with surgery or radiation and have worsened after previous treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires that patients stop taking systemic corticosteroids or other immunosuppressive drugs at least 2 weeks before starting the study treatment, unless they are for adrenal insufficiency at a low dose. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

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

Research has shown that both avelumab and the combination of TG4001 with avelumab have been safe in previous studies. Avelumab alone has generally been well-tolerated by patients with various types of cancer, even those who have undergone multiple treatments.

The combination of TG4001 and avelumab also proved safe. In studies with patients who have advanced HPV16-positive cancers, this combination caused side effects that were usually mild and manageable.

These results suggest that both treatments are considered safe based on past research. However, each person's experience can differ, and ongoing studies carefully monitor safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of TG4001 and Avelumab for treating cancer because it offers a unique approach compared to existing therapies. TG4001 is a therapeutic vaccine engineered to target HPV-related cancers by stimulating the immune system to attack cancer cells, while Avelumab is an immune checkpoint inhibitor that helps the immune system recognize and destroy cancer cells more effectively. This combination could potentially enhance the body's natural defenses against cancer, offering hope for improved outcomes in patients with HPV-positive cancers, unlike standard treatments that primarily rely on surgery, radiation, or chemotherapy.

What evidence suggests that the combination of TG4001 and Avelumab could be effective for HPV-16 positive advanced malignancies?

This trial will compare the effects of Avelumab alone and the combination of TG4001 and Avelumab. Research has shown that combining TG4001 and Avelumab may help treat advanced cancers linked to HPV-16. In one study, this combination helped shrink tumors in 22% of patients who had already received treatment. However, another study found that this combination did not significantly delay the worsening of certain HPV16-positive cancers.

Avelumab alone has proven effective in treating various cancers, such as Merkel cell carcinoma, with good safety and effectiveness. Some studies have shown that Avelumab works well over several years. Overall, while researchers are exploring the potential benefits of combining TG4001 and Avelumab, the results have been mixed so far. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Adults with HPV-16 positive cancers (cervical, vulvar, vaginal, penile, anal) that can't be removed by surgery or cured with radiotherapy. Participants must have a life expectancy of at least 3 months and should not have had more than one prior systemic treatment for their cancer. They need to have measurable disease by CT scan and good organ function. Women must test negative for pregnancy and all participants must use effective contraception.

Inclusion Criteria

My condition cannot be cured with surgery or radiotherapy, and it's getting worse.

Negative blood pregnancy test at screening for women of childbearing potential

I cannot receive platinum-based cancer treatment.

Exclusion Criteria

I do not have serious heart or blood vessel problems.

Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTC), any history of anaphylaxis, or uncontrolled asthma

I have previously received immunotherapy for cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ib Treatment

Safety assessment in cohorts of 3 to 6 patients at increasing doses of TG4001 in combination with avelumab

4 weeks

1 visit (in-person) every 4 weeks

Phase II Part 1 Treatment

Evaluation of efficacy and further evaluation of safety of the combination of TG4001 and avelumab in a single arm

9 months

1 visit (in-person) every 6 weeks

Phase II Part 2 Treatment

Randomized, open-label controlled study comparing TG4001 in combination with avelumab to avelumab alone

9 months

1 visit (in-person) every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment until disease progression, death, or unacceptable toxicity

Up to 3 years

1 visit (in-person) every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• TG4001

Trial Overview The trial is testing TG4001 in combination with Avelumab against Avelumab alone in patients with advanced HPV-16 related cancers. Phase Ib focuses on safety at different doses without dose escalation within patients. Phase II evaluates efficacy and safety in a single-arm study first, then compares the combo to Avelumab alone in a randomized controlled setting.

How Is the Trial Designed?

Group I: TG4001/Avelumab Experimental Treatment 2 Interventions

Group II: Avelumab Experimental Treatment 1 Intervention

Applicable for Phase II part 2.

Avelumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Transgene

Lead Sponsor

Trials

23

Recruited

1,700+

Merck KGaA, Darmstadt, Germany

Industry Sponsor

Trials

449

Recruited

122,000+

Danny Bar-Zohar

Merck KGaA, Darmstadt, Germany

Chief Medical Officer since 2022

MD

Belén Garijo

Merck KGaA, Darmstadt, Germany

Chief Executive Officer since 2021

MD

EMD Serono Research & Development Institute, Inc.

Industry Sponsor

Trials

86

Recruited

22,700+

Miguel Fernández Alcalde

EMD Serono Research & Development Institute, Inc.

Chief Executive Officer

Bachelor’s Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master’s Degree in Management from IESE Business School

Danny Bar-Zohar

EMD Serono Research & Development Institute, Inc.

Chief Medical Officer since 2022

MD

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

Avelumab, a monoclonal antibody targeting PD-L1, demonstrated an acceptable safety profile in a phase 1a trial with 53 patients, with only one dose-limiting toxicity observed at the highest dose of 20 mg/kg, indicating that the maximum tolerated dose was not reached.

The pharmacokinetic analysis showed a dose-proportional exposure and a half-life of approximately 4 days at higher doses, leading to the selection of 10 mg/kg every 2 weeks for further development, as it achieved over 90% target occupancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial. Heery, CR., O'Sullivan-Coyne, G., Madan, RA., et al.[2022]

In a phase 1/2 trial involving 40 patients with recurrent gynecologic cancers, the combination of avelumab and utomilumab was found to be safe, with no serious immune-related adverse events reported.

The objective response rate (ORR) was low at 2.9% overall, but patients with cervical cancer showed a promising ORR of 11% and a disease control rate (DCR) of 78%, suggesting potential for further investigation in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 trial of avelumab combined with utomilumab (4-1BB agonist), PF-04518600 (OX40 agonist), or radiotherapy in patients with advanced gynecologic malignancies. Knisely, A., Ahmed, J., Stephen, B., et al.[2023]

The phase I/IIa study of BMS-986178, an OX40 agonist, showed a manageable safety profile with low rates of severe treatment-related adverse events (5% for monotherapy and up to 15% for combination therapy), indicating it is safe for use in patients with advanced solid tumors.

Despite the safety, the study did not find significant efficacy for BMS-986178 alone or in combination with nivolumab and/or ipilimumab, with no objective responses observed in monotherapy and low response rates (0% to 13%) in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors. Gutierrez, M., Moreno, V., Heinhuis, KM., et al.[2022]

Avelumab is a monoclonal antibody that effectively treats metastatic Merkel cell carcinoma (MCC), showing an objective response rate of 31.8% in a phase II trial with 88 previously treated patients, including 10 complete responses.

The treatment demonstrated a median overall survival of 12.9 months and a 1-year progression-free survival rate of 30%, with manageable side effects, making it a promising alternative to traditional chemotherapy for MCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma. Joseph, J., Zobniw, C., Davis, J., et al.[2020]

Avelumab is an antibody that blocks programmed cell death ligand-1 (PD-L1) and has received accelerated approval in the USA for treating metastatic Merkel cell carcinoma (mMCC) in both adults and children aged 12 and older.

The drug is also undergoing regulatory reviews for other cancer treatments, including urothelial carcinoma, indicating its potential as a versatile cancer therapy in various stages of development worldwide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab: First Global Approval. Kim, ES.[2022]

The JAVELIN Ovarian 200 trial is the first Phase III study to investigate the effectiveness of avelumab, a PD-L1 checkpoint inhibitor, in treating women with platinum-resistant ovarian cancer, involving multiple treatment arms to assess its efficacy.

The trial will measure overall survival and progression-free survival as primary outcomes, providing valuable insights into the potential benefits of avelumab alone or in combination with doxorubicin compared to doxorubicin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design. Pujade-Lauraine, E., Fujiwara, K., Dychter, SS., et al.[2022]

Citations

1. bavencio.com bavencio.com/en_US/patients-and-caregivers/uc-home/about-bavencio/study-results.html

Study Results | BAVENCIO® (avelumab) Efficacy BAVENCIO showed consistent results when the study kept track of patients for over 3 years. BAVENCIO® Long Term Data. BAVENCIO®-Long-Term-Data.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7252959/

Efficacy and safety of avelumab treatment in patients with ... Avelumab, a human anti–programmed death-ligand 1 immunoglobulin G1 monoclonal antibody, showed favorable efficacy and safety in patients with metastatic Merkel ...

3. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-bladder-cancer/158267-asco-gu-2025-real-world-effectiveness-and-safety-of-avelumab-first-line-maintenance-treatment-in-patients-with-locally-advanced-or-metastatic-urothelial-carcinoma-second-interim-analysis-of-the-avenue-study.html

Real-World Effectiveness and Safety of Avelumab First ... AVENUE is a real-world study evaluating the effectiveness and safety of avelumab IL maintenance treatment in routine clinical practice in several countries.

4. bavencio.com bavencio.com/en_US/patients-and-caregivers/mcc-home/clinical-study-results.html

Clinical Study Results | BAVENCIO® (avelumab) Efficacy Efficacy of BAVENCIO® (avelumab) in clinical studies. See how effective BAVENCIO® (avelumab) is for patients with Merkel cell carcinoma.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.584

Real world outcomes for maintenance avelumab treatment ... After a median of six cycles of platinum-based chemotherapy, 11.3% had a complete response, and 54.9% had a partial response. Patients then ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.3055

Avelumab (MSB0010718C; anti-PD-L1) in patients with ... Conclusions: Single-agent avelumab showed an acceptable safety profile in a heavily pretreated population and large dataset of pts with LA/M ...

7. curetoday.com curetoday.com/view/real-world-data-confirms-safety-of-bavencio-and-inlyta-in-advanced-rcc

Real-World Data Confirms Safety of Bavencio and Inlyta in ... Bavencio and Inlyta combination therapy demonstrated high six- and 12-month OS rates in advanced RCC patients in real-world settings. The AVION ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11988210/

Real-world avelumab first-line maintenance in advanced ... Patient characteristics, survival, responses, safety outcomes, and data on treatment patterns and subsequent therapies were extracted.