BNT113 + Pembrolizumab for Head and Neck Cancers

(AHEAD-MERIT Trial)

Recruiting at 223 trial locations

Overseen By BioNTech clinical trial information desk

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: BioNTech SE

Must not be taking: Antibiotics, Corticosteroids, Immunosuppressants, others

Disqualifiers: Pregnancy, Nasopharynx tumor, Uncontrolled illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for certain head and neck cancers that cannot be surgically removed and have returned or spread, specifically those linked to HPV16. Researchers compare the effect of BNT113 (an experimental treatment) combined with pembrolizumab (an immunotherapy drug) to pembrolizumab alone. Part A confirms the safety of the combination, while Part B evaluates its effectiveness compared to the single drug. Suitable participants have tumors that express a specific protein (PD-L1) and have not received certain cancer treatments before. As a Phase 2, Phase 3 trial, this study measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking cancer therapy advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot be on chronic systemic immunosuppressive treatment or certain other therapies close to the start of the trial. It's best to discuss your specific medications with the trial team.

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

Research shows that the combination of BNT113 and pembrolizumab is generally well tolerated by patients. Earlier studies demonstrated that this combination worked effectively and helped determine the best dose for future testing. Participants did not experience unexpected or severe side effects beyond those typically associated with these cancer treatments.

Pembrolizumab alone has FDA approval for treating other cancers, indicating a known history of safe use in many patients.

Overall, for those considering joining this trial, previous research suggests that the BNT113 and pembrolizumab combination is safe and manageable for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancers because BNT113 and pembrolizumab work together in a novel way. Most treatments for these cancers, like chemotherapy and radiation, aim to destroy cancer cells directly but can harm healthy cells too. BNT113 is unique because it is designed to boost the immune system's response specifically to cancer cells when paired with pembrolizumab, which is already known for helping the immune system recognize and attack cancer. This combination could potentially be more targeted and less harmful to healthy tissue, offering a promising new option for patients.

What evidence suggests that this trial's treatments could be effective for head and neck cancers?

Research has shown that combining BNT113 and pembrolizumab, which participants in this trial may receive, may effectively treat certain head and neck cancers linked to HPV16 and PD-L1. Early results suggest this combination can strengthen the immune system, possibly leading to better outcomes. Studies indicate that the treatment is generally well tolerated, which is promising for patients. This trial will compare the combination of BNT113 and pembrolizumab with pembrolizumab monotherapy. While more information is needed, initial findings are hopeful about the combination's potential to improve treatment success compared to using pembrolizumab alone. ^{1 2 3 5 6}

Who Is on the Research Team?

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Are You a Good Fit for This Trial?

Adults over 18 with a specific head and neck cancer (HPV16+ HNSCC) that can't be removed by surgery or has spread, and whose tumors express the PD-L1 protein. Participants must have good liver, kidney, bone marrow function, not had certain treatments before, and women of childbearing age need a negative pregnancy test.

Inclusion Criteria

My tumor is PD-L1 positive as per the FDA-approved test.

My cancer can be measured and has grown in previously treated areas.

My cancer originates in the throat, mouth, or voice box, but not in the upper part of the throat behind the nose.

Exclusion Criteria

Other exclusions

Patients with any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Patients who have a known history (testing not required) or has a positive test at screening of any of the following: Human immunodeficiency virus (HIV) 1 or 2, Hepatitis B (carrier or active infection), Hepatitis C (unless considered cured 5 years post curative anti-viral therapy)

Timeline for a Trial Participant

Pre-screening

Optional pre-screening phase where patients' tumor samples may be submitted for central HPV16 DNA and central PD-L1 expression testing

Not specified

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-In

Initial non-randomized phase to confirm the safety and tolerability of BNT113 in combination with pembrolizumab

Up to 27 months

Randomized Treatment

Randomized phase to generate pivotal efficacy and safety data of BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 48 months

What Are the Treatments Tested in This Trial?

Interventions

• BNT113
• Pembrolizumab

Trial Overview The trial is testing BNT113 combined with pembrolizumab against pembrolizumab alone in patients with HPV16+ HNSCC expressing PD-L1. It's an open-label Phase II study with two parts: initial safety confirmation followed by randomized efficacy comparison.

How Is the Trial Designed?

Group I: Part B (Randomized phase) - BNT113 + Pembrolizumab Experimental Treatment 2 Interventions

BNT113 in combination with pembrolizumab.

Group II: Part A (Safety Run-In) - BNT113 + Pembrolizumab Experimental Treatment 2 Interventions

Safety Run-In Phase to confirm the safety and tolerability at the selected dose range level of BNT113 in combination with pembrolizumab.

Group III: Part B (Randomized phase) - Pembrolizumab monotherapy Active Control 1 Intervention

Pembrolizumab monotherapy.

Who Is Running the Clinical Trial?

BioNTech SE

Lead Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Published Research Related to This Trial

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

In a phase 1b trial involving 60 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, pembrolizumab was found to be well tolerated, with only 17% experiencing severe drug-related adverse events and no drug-related deaths.

The treatment showed clinically meaningful antitumor activity, with an overall response rate of 18%, and particularly higher in HPV-positive patients at 25%, indicating its potential as a viable therapy for advanced head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Seiwert, TY., Burtness, B., Mehra, R., et al.[2022]

In a phase III trial, pembrolizumab, a single-agent treatment, showed significant effectiveness in patients with head and neck tumors that had high PD-L1 expression, leading to deep and lasting responses.

This study highlights the potential of pembrolizumab as a first-line therapy for this specific group of cancer patients, suggesting a targeted approach based on PD-L1 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembro Ups Survival in PD-L1-positive HNSCC. [2019]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

A cost-effectiveness analysis of nivolumab versus pembrolizumab in treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) found that nivolumab has a 56% probability of being cost-effective at a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted life-year (QALY) when dosed at 3 mg/kg biweekly for patients under 72 kg.

For patients over this weight, pembrolizumab is generally the more cost-effective option, especially at higher WTP thresholds, indicating that patient body weight and dosing strategy are crucial factors in treatment decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab vs Pembrolizumab for Treatment of US Patients With Platinum-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Network Meta-analysis and Cost-effectiveness Analysis. Pei, R., Shi, Y., Lv, S., et al.[2021]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04534205

Study Details | NCT04534205 | A Clinical Trial ... Part B, is a randomized part to generate pivotal efficacy and safety data of BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy in the ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02457-8/fulltext

877P Exploratory efficacy and translational results from the ... BNT113 + pembrolizumab was well tolerated, showed encouraging signs of efficacy, and the RP2D was confirmed. We will present serum cytokine and T cell profiling ...

3. ascopubs.org ascopubs.org/doi/10.1200/EDBK_433330

Novel Therapies Beyond PD-L1 Immunotherapy The combination of BNT113 and pembrolizumab is being investigated in the ongoing randomized, phase II, AHEAD-MERIT trial that randomly assigns ...

4. clinicaltrials.biontech.com clinicaltrials.biontech.com/trials/BNT113-01

A Clinical Trial Investigating the Safety, Tolerability, and ... Patients will be treated with BNT113 in combination with pembrolizumab or with pembrolizumab monotherapy for approximately up to 24 months. Medical Condition.

5. medicine.yale.edu medicine.yale.edu/ycci/clinicaltrials/trial/bnt113-01-a-clinical-trial-investigating-the-safety-tolerability-and-therapeutic-effects-of-bnt11/

An Open Label Phase II Randomized Trial of BNT113 in ... Part B, the Randomized part of the trial to generate pivotal efficacy and safety data of BNT113 in combination with pembrolizumab versus ...

6. yalemedicine.org yalemedicine.org/clinical-trials/bnt113-01-a-clinical-trial-investigating-the-safety-tolerability-and-therapeutic-effects-of-bnt11

An Open Label Phase II Randomized Trial of BNT113 ... Part B, the Randomized part of the trial to generate pivotal efficacy and safety data of BNT113 in combination with pembrolizumab versus ...