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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

ConditionsUnresectable Head and Neck Squamous Cell CarcinomaMetastatic Head and Neck CancerRecurrent Head and Neck Cancer
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorBioNTech SE

About 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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).

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.

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • BNT113

    Biological/Vaccine

    IV injection

  • Pembrolizumab

    Biological/Vaccine

    IV infusion

Treatment groups

350 Participants
are divided into 3 treatment groups
Group A: Part A (Safety Run-In) - BNT113 + PembrolizumabExperimental treatment 2 interventions
Group B: Part B (Randomized phase) - BNT113 + PembrolizumabExperimental treatment 2 interventions
Group C: Part B (Randomized phase) - Pembrolizumab monotherapyActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Part A - Occurrence of treatment-emergent adverse event (TEAE) - BNT113 in combination with pembrolizumab

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.

Time frame
up to 27 months
2

Part B - Overall survival (OS)

OS defined as the time from randomization to death from any cause.

Time frame
up to 48 months
3

Part B - Progression-free survival (PFS)

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.

Time frame
up to 48 months

Secondary outcomes

1

Part A and B - Overall response rate (ORR)

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.

Time frame
up to 48 months
2

Part A and B - Duration of response (DOR)

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.

Time frame
up to 48 months
3

Part A - Disease control rate (DCR)

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.

Time frame
up to 48 months
4

Part B - Progression free survival (PFS)

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.

Time frame
up to 48 months

Other outcomes

Sponsors and contacts

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BioNTech SE

Lead sponsor

Source ClinicalTrials.gov
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