TG4001 + Avelumab for Cancer

Recruiting at 19 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

150 Participants Needed

Trial Summary

What is the purpose of this trial?

The study will consist of two parts : In the phase Ib: safety will be assessed in consecutive cohorts of 3 to 6 patients at increasing doses of TG4001 in combination with avelumab according to a 3+3 design. There will be no intra-patient dose escalation. In the phase II part 1, evaluation of efficacy and further evaluation of safety of the combination of TG4001 and avelumab will be performed in a single arm of patients with recurrent or metastatic HPV-16 positive advanced malignancies. In the phase II part 2, evaluation of efficacy of the combination of TG4001 and avelumab will be performed in a randomized, open-label controlled study comparing TG4001 in combination with avelumab to avelumab alone in patients with HPV-16 positive advanced malignancies. In both phases, tumor response will be evaluated on local assessment using RECIST 1.1. All patients will be followed up until disease progression, death, or unacceptable toxicity, or study withdrawal for any reason, whichever occurs first.

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.

What data supports the effectiveness of the drug Avelumab in treating cancer?

Avelumab has been approved in the USA for treating metastatic Merkel cell carcinoma (a rare type of skin cancer) and has shown antitumor activity in patients with advanced solid tumors, including non-small-cell lung cancer. ^{1 2 3 4 5}

Is the combination of TG4001 and Avelumab safe for humans?

Avelumab, also known as Bavencio, has been tested in various trials for different types of cancer and has shown an acceptable safety profile in patients with advanced solid tumors. It is approved for treating metastatic Merkel cell carcinoma and has been studied for other cancers, indicating it is generally safe for human use. ^{1 3 4 6 7}

What makes the drug TG4001 + Avelumab unique for cancer treatment?

The combination of TG4001 and Avelumab is unique because it combines a cancer vaccine (TG4001) with an immune checkpoint inhibitor (Avelumab), which targets PD-L1 to help the immune system attack cancer cells. This approach is novel as it aims to enhance the immune response against cancer by using both a vaccine and a drug that prevents cancer cells from evading immune detection. ^{2 3 4 6 8}

Eligibility Criteria

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.

I cannot receive platinum-based cancer treatment.

Negative blood pregnancy test at screening for women of childbearing potential

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Avelumab: First Global Approval. [2022]

2. United States 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. [2023]

3. England 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and immune-related adverse event associations in avelumab-treated patients. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design. [2022]