RECRUITING

A Clinical Trial Investigating the Safety, Tolerability, and Therapeutic Effects of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Alone for Patients With a Form of Head and Neck Cancer Positive for Human Papilloma Virus 16 and Expressing the Protein PD-L1

Conditions

Unresectable Head and Neck Squamous Cell Carcinoma Metastatic Head and Neck Cancer Recurrent Head and Neck Cancer Cancer vaccine RNA vaccine HNSCC BNT113 Pembrolizumab HPV16 Metastatic Unresectable Recurrent Head and neck mRNA vaccine HPV-positive Head and neck cancer

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

An Open-label Phase II/III Randomized Trial of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Monotherapy as a First Line Therapy in Patients With Unresectable Recurrent, or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Which is Positive for Human Papilloma Virus 16 (HPV16+) and Expresses PD-L1

Quick Facts

Study Start:2021-01-07

Study Completion:2029-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04534205

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Patients must sign the written pre-screening informed consent form (ICF) before any pre-screening procedures. * Patients who present histologically confirmed recurrent or metastatic HPV16+ HNSCC that is considered incurable by local therapies. * Patients who have a tumor that expresses PD-L1 \[CPS ≥1\] as determined by the European Conformity (CE)-marked/Food and Drug Administration-approved CDx PD-L1 immunohistochemistry 22C3 pharmDx performed according to the manufacturer's instructions for use. * Patients must not have had prior systemic anticancer therapy administered in the incurable recurrent or metastatic setting. Systemic therapy which was completed more than 180 days prior to randomization, if given as part of multimodal treatment for locally advanced disease, is allowed. * Patients who have measurable disease based on RECIST 1.1 as determined by the site and confirmed by BICR. Tumor lesions situated in a previously irradiated area may be considered measurable, if progression has been demonstrated in such lesions disease by RECIST 1.1. * All patients must provide a tumor tissue sample (formalin fixed paraffin embedded \[FFPE\] blocks or both slides and curls) from archival tissue. Alternatively, a fresh biopsy sample could be provided if a biopsy sample is performed as part of the patient's standard clinical practice before the first dose of trial treatment. The sample should be preferably derived from a current site of metastatic or recurrent disease. Otherwise, a sample from the primary tumor can be submitted.	* Patients present primary tumor site of nasopharynx (any histology). * Patients with another primary malignancy that has not been in complete remission for at least 2 years, with the exception of those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, non-invasive basal or non-invasive squamous cell skin cancer, localized prostate cancer, non-invasive superficial bladder cancer or breast ductal carcinoma in situ). * Patients who have received or currently receive the following therapy/medication: 1. Chronic systemic immunosuppressive treatment including corticosteroid treatment (prednisone \>10 mg daily orally \[PO\] or intravenously \[IV\], or equivalent) in the 7 days prior to the first dose of trial treatment. 2. Prior treatment with other immune-modulating agents that was (a) within fewer than 4 weeks (28 days) or five half-lives of the agent (whichever is longer) prior to the first dose of BNT113, or (b) associated with immune-mediated AEs that have not resolved prior to the first dose of BNT113 or that pose an additional risk of on-trial complications, per investigator's assessment, or c) associated with toxicity that resulted in discontinuation of the immune-modulating agent and that poses an additional risk of on-trial complications, per investigator's assessment. 3. Prior treatment with live attenuated vaccines within 4 weeks before the first dose of BNT113. 4. Prior treatment with an investigational drug (including investigational vaccines) within 4 weeks or five half-lives of the agent (whichever is longer) before the planned first dose of BNT113. 5. Ongoing treatment with therapeutic PO or IV antibiotics. Note: Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) may be enrolled. * Prior treatment with anti-cancer immunomodulating agents, such as blockers of programmed death receptor-1 (PD-1), PD-L1, tumor necrosis factor receptor superfamily member 9 (TNRSF9, 4 1BB, CD137), OX 40, therapeutic vaccines, cytokine treatments, or any investigational agent within 4 weeks or five half-lives of the agent (whichever is longer) before the first dose of BNT113. * Treatment with non-systemic anti-cancer therapy (e.g., radiotherapy or surgery) within 2 weeks prior to randomization. Note: Prior treatment with bone resorptive therapy, such as bisphosphonates (e.g., pamidronate, zoledronic acid) and denosumab, is allowed.

Inclusion Criteria

Exclusion Criteria

* Patients must sign the written pre-screening informed consent form (ICF) before any pre-screening procedures.
* Patients who present histologically confirmed recurrent or metastatic HPV16+ HNSCC that is considered incurable by local therapies.
* Patients who have a tumor that expresses PD-L1 \[CPS ≥1\] as determined by the European Conformity (CE)-marked/Food and Drug Administration-approved CDx PD-L1 immunohistochemistry 22C3 pharmDx performed according to the manufacturer's instructions for use.
* Patients must not have had prior systemic anticancer therapy administered in the incurable recurrent or metastatic setting. Systemic therapy which was completed more than 180 days prior to randomization, if given as part of multimodal treatment for locally advanced disease, is allowed.
* Patients who have measurable disease based on RECIST 1.1 as determined by the site and confirmed by BICR. Tumor lesions situated in a previously irradiated area may be considered measurable, if progression has been demonstrated in such lesions disease by RECIST 1.1.
* All patients must provide a tumor tissue sample (formalin fixed paraffin embedded \[FFPE\] blocks or both slides and curls) from archival tissue. Alternatively, a fresh biopsy sample could be provided if a biopsy sample is performed as part of the patient's standard clinical practice before the first dose of trial treatment. The sample should be preferably derived from a current site of metastatic or recurrent disease. Otherwise, a sample from the primary tumor can be submitted.

* Patients present primary tumor site of nasopharynx (any histology).
* Patients with another primary malignancy that has not been in complete remission for at least 2 years, with the exception of those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, non-invasive basal or non-invasive squamous cell skin cancer, localized prostate cancer, non-invasive superficial bladder cancer or breast ductal carcinoma in situ).
* Patients who have received or currently receive the following therapy/medication:
1. Chronic systemic immunosuppressive treatment including corticosteroid treatment (prednisone \>10 mg daily orally \[PO\] or intravenously \[IV\], or equivalent) in the 7 days prior to the first dose of trial treatment.
2. Prior treatment with other immune-modulating agents that was (a) within fewer than 4 weeks (28 days) or five half-lives of the agent (whichever is longer) prior to the first dose of BNT113, or (b) associated with immune-mediated AEs that have not resolved prior to the first dose of BNT113 or that pose an additional risk of on-trial complications, per investigator's assessment, or c) associated with toxicity that resulted in discontinuation of the immune-modulating agent and that poses an additional risk of on-trial complications, per investigator's assessment.
3. Prior treatment with live attenuated vaccines within 4 weeks before the first dose of BNT113.
4. Prior treatment with an investigational drug (including investigational vaccines) within 4 weeks or five half-lives of the agent (whichever is longer) before the planned first dose of BNT113.
5. Ongoing treatment with therapeutic PO or IV antibiotics. Note: Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) may be enrolled.
* Prior treatment with anti-cancer immunomodulating agents, such as blockers of programmed death receptor-1 (PD-1), PD-L1, tumor necrosis factor receptor superfamily member 9 (TNRSF9, 4 1BB, CD137), OX 40, therapeutic vaccines, cytokine treatments, or any investigational agent within 4 weeks or five half-lives of the agent (whichever is longer) before the first dose of BNT113.
* Treatment with non-systemic anti-cancer therapy (e.g., radiotherapy or surgery) within 2 weeks prior to randomization. Note: Prior treatment with bone resorptive therapy, such as bisphosphonates (e.g., pamidronate, zoledronic acid) and denosumab, is allowed.

Contacts and Locations

Study Contact

BioNTech clinical trials patient information

CONTACT

+49 6131 9084

patients@biontech.de

Principal Investigator

BioNTech Responsible Person

STUDY_DIRECTOR

BioNTech SE

Study Locations (Sites)

California Research Institute

Los Angeles, California, 90027

United States

UCLA Cancer Care

Los Angeles, California, 90095

United States

Stanford Cancer Institute

Palo Alto, California, 94304

United States

Yale University

New Haven, Connecticut, 06511

United States

The George Washington Cancer Center

Washington, District of Columbia, 20052

United States

University of Miami Miller School of Medicine

Plantation, Florida, 33324-3274

United States

University of Miami Miller School of Medicine

Plantation, Florida, 33324

United States

University Cancer and Blood Center

Athens, Georgia, 30607

United States

Winship Cancer Institute

Atlanta, Georgia, 30322

United States

Norton Cancer Institute

Louisville, Kentucky, 40241

United States

Tufts Medical Center

Boston, Massachusetts, 02111

United States

The University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131

United States

Montefiore Medical Center

Bronx, New York, 10467

United States

Icahn School of Medicine at Mount Sinai

New York, New York, 10029

United States

University of Cincinnati Cancer Center

Cincinnati, Ohio, 45219

United States

Providence Cancer Institute

Portland, Oregon, 97213

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

MultiCare Regional Cancer Center

Tacoma, Washington, 98405

United States

Collaborators and Investigators

Sponsor: BioNTech SE

BioNTech Responsible Person, STUDY_DIRECTOR, BioNTech SE

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-01-07

Study Completion Date2029-04

Study Record Updates

Study Start Date2021-01-07

Study Completion Date2029-04

Terms related to this study

Keywords Provided by Researchers

Cancer vaccine
RNA vaccine
HNSCC
BNT113
Pembrolizumab
HPV16
Metastatic
Unresectable
Recurrent
Head and neck
mRNA vaccine
HPV-positive
Head and neck cancer

Additional Relevant MeSH Terms

Unresectable Head and Neck Squamous Cell Carcinoma
Metastatic Head and Neck Cancer
Recurrent Head and Neck Cancer