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

NCT04534205 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: BNT113-012020-001400-412024-512671-12-00
• Study Type: interventional
• Target: 358
• Locations: 20 countries
• Sites: 136

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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.

  up to 27 months

• Part B - Overall survival (OS)

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

  up to 48 months

• 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.

  up to 48 months

Secondary Outcomes (8)

• Part A and B - Overall response rate (ORR)

  up to 48 months

• Part A and B - Duration of response (DOR)

  up to 48 months

• Part A - Disease control rate (DCR)

  up to 48 months

• Part B - Progression free survival (PFS)

  up to 48 months

• Part B - PFS rate at 6 months

  from randomization until 6 months after randomization

Study Arms (3)

Part A (Safety Run-In) - BNT113 + Pembrolizumab

EXPERIMENTAL

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

Biological: BNT113; Biological: Pembrolizumab

Part B (Randomized phase) - BNT113 + Pembrolizumab

EXPERIMENTAL

BNT113 in combination with pembrolizumab.

Biological: BNT113; Biological: Pembrolizumab

Part B (Randomized phase) - Pembrolizumab monotherapy

ACTIVE COMPARATOR

Pembrolizumab monotherapy.

Biological: Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Part A (Safety Run-In) - BNT113 + Pembrolizumab; Part B (Randomized phase) - BNT113 + Pembrolizumab; Part B (Randomized phase) - Pembrolizumab monotherapy

BNT113 BIOLOGICAL

IV injection

Part A (Safety Run-In) - BNT113 + Pembrolizumab; Part B (Randomized phase) - BNT113 + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.
• Prior treatment with live attenuated vaccines within 4 weeks before the first dose of BNT113.
• 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.
• 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.

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (142)

UCLA Cancer Care

Los Angeles, California, 90095, United States

Location

Stanford Cancer Institute

Palo Alto, California, 94304, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

The George Washington Cancer Center

Washington D.C., District of Columbia, 20052, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40241, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

The University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Memorial Sloan Kettering Cancer Center

Long Island City, New York, 11101, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of Cincinnati Cancer Center

Cincinnati, Ohio, 45219, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Centro de Oncología e Investigación Buenos Aires COIBA

Berazategui, B1884BBF, Argentina

Location

Instituto de Oncologia de Cordoba

Córdoba, X500AA1, Argentina

Location

Centro Oncologico Riojano Integral

La Rioja, 5300, Argentina

Location

Centro de Investigacion Pergamino SA - Clinica Pergamino

Pergamino, 2700, Argentina

Location

Instituto de Oncologia de Rosario

Rosario, 2000, Argentina

Location

Sanatorio Britanico

Rosario, 2000, Argentina

Location

CAIPO Centro para la Atencion Integral del Paciente Oncologico

San Miguel de Tucumán, 4000, Argentina

Location

Cancer Research SA

Adelaide, 5000, Australia

Location

Flinders Medical Centre

Bedford Park, 5042, Australia

Location

St Vincent's Hospital

Fitzroy, VIC 3065, Australia

Location

Royal North Shore Hospital

Saint Leonards, 2065, Australia

Location

John Flynn Private Hospital

Tugun, 4224, Australia

Location

Southern Medical Day Care Centre

Wollongong, 2500, Australia

Location

LKH - Univ. Klinikum Graz

Graz, 8036, Austria

Location

Landeskrankenhaus/ Univ.-Kliniken Innsbruck

Innsbruck, 6020, Austria

Location

HNO, Kopf-und Halschirurgie Ordensklinikum Linz Barmherzigen Schwestern

Linz, 4010, Austria

Location

Uniklinikum Salzburg, Univ. Klinik fur Innere Medizin III

Salzburg, 5020, Austria

Location

Universitair Ziekenhuis Brussel

Brussels, 1090, Belgium

Location

Universitair Ziekenhuis Gent UZ Gent

Ghent, 9000, Belgium

Location

CHR de la Citadelle

Liège, 4000, Belgium

Location

Fundação PIO XII - Hospital de Amor Barretos

Barretos, 14784-400, Brazil

Location

Oncocentro - Grupo Oncoclinicas

Belo Horizonte, 30360-680, Brazil

Location

Fundacao Universidade de Caxias do Sul - Instituto de Pesquisas em Saude IPS-UCS

Caxias do Sul, 95070-560, Brazil

Location

Hospital Erasto Gaertner

Curitiba, 81520-060, Brazil

Location

Oncosite - Centro de Pesquisa Clinica em Oncologia

Ijuí, 98700-000, Brazil

Location

Hospital Marcio Cunha

Ipatinga, 35162-189, Brazil

Location

Irmandade Santa Casa de Misericordia de Porto Alegre Hospital Santa Rita

Porto Alegre, 90050-170, Brazil

Location

Hospital Mae de Deus

Porto Alegre, 90110-270, Brazil

Location

Hospital Sao Lucas da PUCRS

Porto Alegre, 90610-000, Brazil

Location

Instituto Nacional de Cancer Jose de Alencar Gomes da Silva - INCA

Rio de Janeiro, 20231-050, Brazil

Location

Nucleo de Oncologia da Bahia

Salvador, 40170-070, Brazil

Location

Hospital Sao Rafael

Salvador, 41253-190, Brazil

Location

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, 15090-000, Brazil

Location

Instituto do Cancer do Estado de São Paulo

São Paulo, 01246-000, Brazil

Location

IBCC - Instituto Brasileiro de Controle do Cancer

Vila Mariana, 04014-002, Brazil

Location

Cross Cancer Institute

Edmonton, T6G 1Z2, Canada

Location

British Columbia Cancer Agency

Kelowna, V1Y 5L3, Canada

Location

Jewish General Hospital

Montreal, H3T 1E2, Canada

Location

McGill University Health Centre

Montreal, H4A 3J1, Canada

Location

Centro de Estudios Clinicos SAGA

Santiago, 7500653, Chile

Location

Fundación Arturo López Pérez

Santiago, 7500921, Chile

Location

Fakultni Nemocnice Olomouc

Olomouc, 779 00, Czechia

Location

Hospital Na Bulovce (Nemocnice na Bulovce)

Prague 8 - Liben, 180 00, Czechia

Location

CHU de BORDEAUX, Hopital Saint Andre

Bordeaux, 33075, France

Location

CHU de Caen Normandie

Caen, 14033, France

Location

Centre Georges Francois Leclerc

Dijon, 21079, France

Location

Hopital de la Timone

Marseille, 13005, France

Location

Institut Curie

Paris, 75005, France

Location

Institut Curie, Groupe Hospitalier Paris Saint-Joseph (GHPSJ)

Paris, 75014, France

Location

CHU de Tours Hopital Bretonneau

Tours, 37044, France

Location

Hospital Gustave Roussy

Villejuif, 94800, France

Location

Charite Universitätsklinikum Berlin - Campus Benjamin Franklin

Berlin, 13353, Germany

Location

Klinik für HNO-Heilkunde, Kopf- und Hals-Chirurgie

Cologne, 50937, Germany

Location

Medizinische Hochschule Hannover (MHH)

Hanover, 30625, Germany

Location

Universitaetsklinik Heidelberg

Heidelberg, 69124, Germany

Location

St. Josefs-Hospital, Katholisches Krankenhaus Hagen gem. GmbH

Iserlohn, 58638, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

UNIVERSITAETSMEDIZIN der Johannes Gutenberg-Universitaet Mainz

Mainz, 55131, Germany

Location

Klinikum rechts der Isar der TUM

München, 81675, Germany

Location

Univeritätsklinikum Münster

Münster, 48149, Germany

Location

Universitaetsmedizin Rostock - Medizinische Klink III (Hamatologie, Onkologie, Palliativmedizin)

Rostock, 18057, Germany

Location

Caritas Klinikum Saarbrucken St. Theresia

Saarbrücken, 66113, Germany

Location

Medizinische Universitaetsklinik Tuebingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm, Klinik für Hals-Nasen- Ohrenheilkunde und Kopf-Halschirurgie

Ulm, 89081, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, 97080, Germany

Location

Central Hospital of Northern Pest - Military Hospital

Budapest, 1062, Hungary

Location

Rambam Health Clinical

Haifa, 3109601, Israel

Location

Hadassah Medical Center - Sharett Institute of Oncology

Jerusalem, 49100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

ASST Spedali Civili Brescia

Brescia, 25123, Italy

Location

Mater Salutis Hospital AULSS 9 della Regione Veneto

Legnago, 37045, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

IRCCS Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Centro de Estudios y Prevención del Cáncer (CEPREC)

Tuxtla Gutiérrez, Region Chiapas, 29038, Mexico

Location

Centro Estatal de Cancerologia de Chihuahua

Chihuahua City, 31000, Mexico

Location

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, 44280, Mexico

Location

Cryptex Investigacion SA de CV

Mexico City, 06100, Mexico

Location

Consultorio del Dr. Joaquín Gabriel Reinoso Toledo

Monterrey, 64320, Mexico

Location

Hospital Universitario "Dr Jose Eleuterio Gonzalez" Centro Universitario contra el Cáncer

Monterrey, 64460, Mexico

Location

Oaxaca Site Management Organization S. C.

Oaxaca City, 68000, Mexico

Location

Sociedad de Metabolismo y Corazón S.C.

Veracruz, 91900, Mexico

Location

Centro de Atencion e Investigacion Clinica en Oncologia (CAICO)

Yucatán, 97134, Mexico

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie

Gliwice, 44-102, Poland

Location

Przychodnia Lekarska KOMED Roman Karaszewski

Konin, 62-500, Poland

Location

Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ

Wroclaw, 50-981, Poland

Location

Instituto Português de Oncologia de Coimbra Francisco Gentil, E.P.E.

Coimbra, 3000-075, Portugal

Location

IPO Lisboa Francisco Gentil

Lisbon, 1099-023, Portugal

Location

Centro Hospitalar Universitario Lisboa Norte

Lisbon, 1649-028, Portugal

Location

Chonnam National University Hwasun Hospital

Hwasun, 58128, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

The Catholic University of Korea, Seoul ST. Mary's Hospital

Seoul, 06591, South Korea

Location

The Catholic University of Korea St. Vincent's Hospital

Suwon, 16247, South Korea

Location

Ajou University Hospital

Suwon, 16499, South Korea

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Hospital Univ. Dr. Josep Trueta

Girona, 17007, Spain

Location

Complejo Hospitalario de Jaen

Jaén, 23007, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, 28222, Spain

Location

Hospital Regional de Malaga

Málaga, 29010, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, 07120, Spain

Location

Hospital La Fe

Valencia, 46026, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80708, Taiwan

Location

Chang Gung Memorial Hospital-Kaohsiung Branch

Kaohsiung City, 833401, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 407219, Taiwan

Location

National Taiwan University Hospital

Taipei, 100225, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

Location

Belfast Health and Social Care Trust, Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

University Hospitals Birmingham, Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Addenbrooke's Hospital - Cambridge University Hospitals

Cambridge, CB2 0QQ, United Kingdom

Location

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust (St James's University Hospital)

Leeds, LS9 7TF, United Kingdom

Location

The Clatterbridge Cancer Centre

Liverpool, L7 8YA, United Kingdom

Location

University College London Hospitals

London, NW 12 PG, United Kingdom

Location

Guy's Cancer Centre, Guy's Hospital

London, SE1 9RT, United Kingdom

Location

The Royal Marsden Hospital NHS Foundation Trust - Fulham Road

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

Oxford Cancer Centre

Oxford, OX3 7LE, United Kingdom

Location

Royal Preston Hospital Lancashire Teaching Hospitals NHS Foundation Trust

Preston, PR2 9HT, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

Location

Mount Vernon Cancer Centre, East and North Hertfordshire NHS Trust

Stevenage, SG1 4AB, United Kingdom

Location

The Royal Marsden Hospital - Sutton

Sutton, SM2 5PT, United Kingdom

Location

Torbay Hospital - South Devon Healthcare NHS Foundation Trust

Torquay, TQ2 7AA, United Kingdom

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Neoplasm Metastasis; Recurrence

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2020
• First Posted: September 1, 2020
• Study Start: January 7, 2021
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: September 21, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

AR (7); PL (4); ME (9); IT (4); IL (3); BR (15); DE (14); AU (4); PT (3); CL (2); ES (8); BE (3); US (15); HU (1); KR (6); GB (19); FR (8); TW (5); CA (4); CZ (2)