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

Phase 2

Recruiting

• Conditions: Unresectable Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Cancer; Recurrent Head and Neck Cancer
• Interventions: Biological: BNT113; Biological: Pembrolizumab

• Registration Number: NCT04534205
• Lead Sponsor: BioNTech SE

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-08-27
• Study First Submitted QC: 2020-08-27
• Study First Posted: 2020-09-01
• Study Start: 2021-01-07
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-10
• Last Update Posted: 2025-07-11
• Primary Completion: 2029-04
• Study Completion: 2029-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 350

Inclusion 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.

Key

Exclusion Criteria

Medical conditions:

• 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).

Prior/concomitant therapy:

• 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A (Safety Run-In) - BNT113 + Pembrolizumab	BNT113	Safety Run-In Phase to confirm the safety and tolerability at the selected dose range level of BNT113 in combination with pembrolizumab.
Part A (Safety Run-In) - BNT113 + Pembrolizumab	Pembrolizumab	Safety Run-In Phase to confirm the safety and tolerability at the selected dose range level of BNT113 in combination with pembrolizumab.
Part B (Randomized phase) - BNT113 + Pembrolizumab	BNT113	BNT113 in combination with pembrolizumab.
Part B (Randomized phase) - BNT113 + Pembrolizumab	Pembrolizumab	BNT113 in combination with pembrolizumab.
Part B (Randomized phase) - Pembrolizumab monotherapy	Pembrolizumab	Pembrolizumab monotherapy.

Primary Outcome Measures

Name	Time	Method
Part A - Occurrence of treatment-emergent adverse event (TEAE) - BNT113 in combination with pembrolizumab	up to 27 months	TEAE assessed according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) including Grade ≥3, serious, and fatal TEAEs, by relationship.
Part B - Overall survival (OS)	up to 48 months	OS defined as the time from randomization to death from any cause.
Part B - Progression-free survival (PFS)	up to 48 months	PFS defined as the time from randomization to the first objective tumor progression (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\] assessed by the blinded independent central review \[BICR\]), or death from any cause, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Part A and B - Overall response rate (ORR)	up to 48 months	ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) (per RECIST 1.1 assessed by BICR and investigator) is observed as best overall response.
Part A and B - Duration of response (DOR)	up to 48 months	DOR defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (progressive disease \[PD\] per RECIST 1.1) or death from any cause, whichever occurs first. In Part A, assessment will be done by both BICR and investigator; in Part B, only by BICR.
Part A - Disease control rate (DCR)	up to 48 months	DCR defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1, assessed at least 6 weeks after first dose by BICR and investigator) is observed as best overall response.
Part B - Progression free survival (PFS)	up to 48 months	PFS defined as the time from randomization to the first objective tumor progression (per RECIST 1.1 by investigator's assessment) or death from any cause, whichever occurs first.
Part B - PFS rate at 6 months	from randomization until 6 months after randomization	Defined as the proportion of patients without objective tumor progression (per RECIST 1.1 assessed by BICR and investigator) or death from any cause
Part B - PFS rate at 12 months	from randomization until 12 months after randomization	Defined as the proportion of patients without objective tumor progression (per RECIST 1.1 assessed by BICR and investigator) or death from any cause.
Part B - Occurrence of TEAEs - BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy	up to 27 months	TEAEs assessed according to CTCAE v5.0 including Grade ≥3, serious, and fatal TEAEs by relationship.
Part B - Occurrence of dose reduction, delay, and discontinuation of trial treatments due to TEAEs	up to 27 months	BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy.

Trial Locations

Locations (186)

California Research Institute; 🇺🇸 Los Angeles, California, United States

UCLA Cancer Care; 🇺🇸 Los Angeles, California, United States

Stanford Cancer Institute; 🇺🇸 Palo Alto, California, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

The George Washington Cancer Center; 🇺🇸 Washington, District of Columbia, United States

University of Miami Miller School of Medicine; 🇺🇸 Plantation, Florida, United States

University Cancer and Blood Center; 🇺🇸 Athens, Georgia, United States

Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

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