BNT113 + Pembrolizumab for Head and Neck Cancers

(AHEAD-MERIT Trial)

Recruiting in Palo Alto (17 mi)

+193 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: BioNTech SE

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

Disqualifiers: Pregnancy, Nasopharynx tumor, Uncontrolled illness, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

An open-label, controlled, multi-site, interventional, 2-arm, Phase II/III trial of BNT113 in combination with pembrolizumab vs pembrolizumab monotherapy as first line treatment in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing programmed cell death ligand-1 (PD-L1) with combined positive score (CPS) ≥1. This trial has two parts. Part A, is an initial non-randomized Safety Run-In Phase to confirm the safety and tolerability at the selected dose range level of BNT113 in combination with pembrolizumab. Part B, is a randomized part to generate pivotal efficacy and safety data of BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy in the first line setting in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing PD-L1 with CPS ≥1. Patients included in the Safety Run-In Phase of the trial (Part A) will not be randomized to Part B and will continue on-trial treatment (BNT113 plus pembrolizumab) within Part A. For Part B, an optional pre-screening phase is available for all patients where patients' tumor samples may be submitted for central HPV16 DNA and central PD-L1 expression testing prior to screening into the main trial. Patients will be treated with BNT113 in combination with pembrolizumab or with pembrolizumab monotherapy for approximately up to 24 months.

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.

What data supports the effectiveness of the drug pembrolizumab for head and neck cancers?

Research shows that pembrolizumab, when used alone or with chemotherapy, is effective in treating head and neck squamous cell carcinoma, especially in tumors with high levels of PD-L1, a protein that helps cancer cells hide from the immune system. ^{1 2 3 4 5}

Is the combination of BNT113 and Pembrolizumab safe for treating head and neck cancers?

Pembrolizumab, also known as KEYTRUDA, has been evaluated for safety in patients with head and neck cancers. Common serious side effects include pneumonia, breathing difficulties, confusion, vomiting, fluid around the lungs, and respiratory failure. Other significant immune-related side effects can affect the lungs, liver, adrenal glands, blood sugar levels, skin, muscles, and thyroid. ^{2 6 7 8 9}

What makes the drug BNT113 + Pembrolizumab unique for head and neck cancers?

The combination of BNT113 and Pembrolizumab is unique because it combines a novel mRNA-based cancer vaccine (BNT113) with an immune checkpoint inhibitor (Pembrolizumab), which blocks the PD-1 pathway to help the immune system attack cancer cells. This approach is different from traditional chemotherapy and offers a new way to treat head and neck cancers by potentially enhancing the immune response against the tumor. ^{1 3 5 6 7}

Research Team

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Eligibility Criteria

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)

Trial Timeline

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

Treatment Details

Interventions

• BNT113 (Other)
• Pembrolizumab (PD-L1 Inhibitor)

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. England 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. [2021]

3. United States 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. [2023]

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

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

5. United States 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. [2021]

6. England 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. [2019]

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

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

8. England 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. [2022]

9. England 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. [2021]