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 (AHEAD-MERIT)

An Open Label Phase II 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 (AHEAD-MERIT)

An open-label, controlled, multi-site, interventional, 2-arm, Phase II 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, 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, the Randomized part of the trial 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.

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.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Head and Neck Cancer; Unresectable Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Cancer
• Intervention / Treatment: Biological: Pembrolizumab; Biological: BNT113

• Study Type: Interventional
• Enrollment (Estimated): 285
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: BioNTech clinical trials patient information; Phone Number: +49 6131 9084; Email: patients@biontech.de

Study Locations

• Argentina
  • Berazategui, Argentina, B1884BBF
    • Recruiting
    • Centro de Oncología e Investigación Buenos Aires COIBA
  • Ciudad de Buenos Aires, Argentina, 1280
    • Recruiting
    • Hospital Britanico de Buenos Aires
  • Córdoba, Argentina, X500AA1
    • Recruiting
    • Instituto de Oncologia de Cordoba
  • La Rioja, Argentina, 5300
    • Recruiting
    • Centro Oncologico Riojano Integral
  • Pergamino, Argentina, 2700
    • Recruiting
    • Centro de Investigacion Pergamino SA - Clinica Pergamino
  • Rosario, Argentina, 2000
    • Recruiting
    • Sanatorio Britanico
  • Rosario, Argentina, 2000
    • Recruiting
    • Instituto de Oncología de Rosario
  • San Miguel De Tucumán, Argentina, 4000
    • Recruiting
    • CAIPO Centro para la Atencion Integral del Paciente Oncologico
  • Viedma, Argentina, 8500
    • Recruiting
    • Clínica Viedma
• Australia
  • Adelaide, Australia, 5000
    • Recruiting
    • Cancer Research Sa
  • Bankstown, Australia, 2200
    • Withdrawn
    • Bankstown-Lidcombe Hospital
  • Bedford Park, Australia, 5042
    • Recruiting
    • Flinders Medical Centre
  • Coffs Harbour, Australia, 2450
    • Recruiting
    • Coffs Harbour Hospital
  • Fitzroy, Australia, VIC 3065
    • Recruiting
    • St Vincent's Hospital
  • Saint Leonards, Australia, 2065
    • Recruiting
    • Royal North Shore Hospital
  • Tugun, Australia, 4224
    • Recruiting
    • John Flynn Private Hospital
  • Wollongong, Australia, 2500
    • Recruiting
    • Southern Medical Day Care Centre
• Austria
  • Graz, Austria, 8036
    • Recruiting
    • LKH - Univ. Klinikum Graz
  • Innsbruck, Austria, 6020
    • Recruiting
    • Landeskrankenhaus/ Univ.-Kliniken Innsbruck
  • Linz, Austria, 4010
    • Recruiting
    • HNO, Kopf-und Halschirurgie Ordensklinikum Linz Barmherzigen Schwestern
  • Salzburg, Austria, 5020
    • Recruiting
    • Uniklinikum Salzburg, Univ. Klinik fur Innere Medizin III
• Belgium
  • Bruxelles, Belgium, 1090
    • Recruiting
    • Universitair Ziekenhuis Brussel
  • Gent, Belgium, 9000
    • Recruiting
    • Universitair Ziekenhuis Gent UZ Gent
  • Liège, Belgium, 4000
    • Recruiting
    • CHR de la CITADELLE
• Brazil
  • Barretos, Brazil, 14784-400
    • Recruiting
    • Fundação PIO XII - Hospital de Amor Barretos
  • Caxias Do Sul, Brazil, 95070-560
    • Recruiting
    • Fundacao Universidade de Caxias do Sul - Instituto de Pesquisas em Saude IPS-UCS
  • Curitiba, Brazil, 81520-060
    • Recruiting
    • Hospital Erasto Gaertner
  • Ijuí, Brazil, 98700-000
    • Recruiting
    • Hospial de Caridade de Ijui
  • Ipatinga, Brazil, 35162-189
    • Recruiting
    • Hospital Marcio Cunha
  • Porto Alegre, Brazil, 90610-000
    • Recruiting
    • Hospital São Lucas da PUCRS
  • Porto Alegre, Brazil, 90050-170
    • Recruiting
    • Irmandade Santa Casa de Misericordia de Porto Alegre Hospital Santa Rita
  • Porto Alegre, Brazil, 90110-270
    • Recruiting
    • Hospital Mae de Deus
  • Rio De Janeiro, Brazil, 20231-050
    • Recruiting
    • Instituto Nacional de Câncer José de Alencar Gomes da Silva - INCA
  • Salvador, Brazil, 41253-190
    • Recruiting
    • Hospital Sao Rafael
  • São José Do Rio Preto, Brazil, 15090-000
    • Recruiting
    • Hospital de Base de São José do Rio Preto
  • São Paulo, Brazil, 01246-000
    • Recruiting
    • Instituto do Cancer do Estado de Sao Paulo
  • Vila Mariana, Brazil, 04014-002
    • Recruiting
    • IBCC - Instituto Brasileiro de Controle do Câncer
• Canada
  • Edmonton, Canada, T6G 1Z2
    • Recruiting
    • Cross Cancer Institute
  • Montreal, Canada, H3T 1E2
    • Recruiting
    • Jewish General Hospital
  • Montréal, Canada, H4A 3J1
    • Recruiting
    • McGill University Health Centre
  • Toronto, Canada, M5G 2C1
    • Recruiting
    • Princess Margaret Cancer Centre
• Chile
  • Santiago, Chile, 7500921
    • Recruiting
    • Fundacion Arturo Lopez Perez
  • Santiago, Chile, 7500653
    • Recruiting
    • Centro de Estudios Clínicos SAGA
  • Temuco, Chile, 4800827
    • Recruiting
    • James Lind Centro de Investigacion Del Cancer
• Czechia
  • Olomouc, Czechia, 779 00
    • Recruiting
    • Fakultni nemocnice Olomouc
  • Prague 8 - Liben, Czechia, 180 00
    • Recruiting
    • Hospital Na Bulovce (Nemocnice na Bulovce)
• France
  • Bordeaux, France, 33075
    • Recruiting
    • CHU de BORDEAUX, Hopital Saint Andre
  • Dijon Cedex, France, 21079
    • Recruiting
    • Centre GEORGES FRANÇOIS LECLERC
  • Marseille, France, 13005
    • Recruiting
    • Hopital de la Timone
  • Nantes, France, 44277
    • Recruiting
    • Hôpital Privé du Confluent
  • Paris, France, 75005
    • Recruiting
    • Institut Curie
  • Paris, France, 75014
    • Recruiting
    • Institut Curie, Groupe Hospitalier Paris Saint-Joseph (GHPSJ)
  • Tours, France, 37044
    • Recruiting
    • CHU de Tours Hopital Bretonneau
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charite Universitätsklinikum Berlin - Campus Benjamin Franklin
  • Frankfurt am Main, Germany, 60488
    • Recruiting
    • Krankenhaus Nordwest Gmbh
  • Hamburg, Germany, 40878
    • Recruiting
    • Kath. Marien Krankenhaus gGmbH
  • Hamburg, Germany, 07548
    • Withdrawn
    • SRH Wald-Klinikum Gera GmbH
  • Heidelberg, Germany, 69124
    • Recruiting
    • Universitaetsklinik Heidelberg
  • Köln, Germany, 50937
    • Recruiting
    • Klinik für HNO-Heilkunde, Kopf- und Hals-Chirurgie
  • Leipzig, Germany, 04103
    • Recruiting
    • Universitatsklinikum Leipzig
  • München, Germany, 81675
    • Recruiting
    • Klinikum rechts der Isar der TUM
  • Münster, Germany, 48149
    • Recruiting
    • Univeritätsklinikum Münster
  • Rostock, Germany, 18057
    • Recruiting
    • Universitaetsmedizin Rostock - Medizinische Klink III (Hamatologie, Onkologie, Palliativmedizin)
  • Saarbruecken, Germany, 66113
    • Recruiting
    • Caritas Klinikum Saarbrucken St. Theresia
  • Tübingen, Germany, 72076
    • Recruiting
    • Medizinische Universitaetsklinik Tuebingen
  • Würzburg, Germany, 97080
    • Recruiting
    • Universitaetsklinikum Wuerzburg
• Hungary
  • Budapest, Hungary, 1145
    • Recruiting
    • Uzsoki Utcai Korhaz Onkologiai Osztaly
  • Budapest, Hungary, 1062
    • Recruiting
    • Central Hospital of Northern Pest - Military Hospital
  • Debrecen, Hungary, 4032
    • Withdrawn
    • DEKK Onkologiai Klinika
  • Zalaegerszeg, Hungary, 8900
    • Recruiting
    • Zala Megyei S. Rafael Korhaz
• Italy
  • Brescia, Italy, 25123
    • Recruiting
    • ASST Spedali Civili Brescia
  • Legnago, Italy, 37045
    • Recruiting
    • Mater Salutis Hospital AULSS 9 della Regione Veneto
  • Milano, Italy, 20132
    • Recruiting
    • IRCCS Ospedale San Raffaele
  • Milano, Italy, 20141
    • Recruiting
    • IRCCS Istituto Europeo di Oncologia
  • Napoli, Italy, 80147
    • Recruiting
    • Ospedale del Mare
  • Novara, Italy, 28100
    • Recruiting
    • A.O.U. Maggiore della Carità
  • Siena, Italy, 53100
    • Recruiting
    • Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
  • Udine, Italy, 33100
    • Recruiting
    • Azienda Sanitaria Universitaria Integrata Friuli Centrale - Presidio ospedaliero di Udine
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35015
    • Recruiting
    • Chungnam National University Hospital
  • Hwasun, Korea, Republic of, 58128
    • Recruiting
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of, 02841
    • Recruiting
    • Korea University Anam Hospital
  • Suwon-si, Korea, Republic of, 16499
    • Recruiting
    • Ajou University Hospital
  • Suwon-si, Korea, Republic of, 16247
    • Recruiting
    • The Catholic University Of Korea St. Vincent's Hospital
• Mexico
  • Chihuahua, Mexico, 31000
    • Recruiting
    • Centro Estatal de Cancerologia de Chihuahua
  • Ciudad De México, Mexico, 06100
    • Recruiting
    • Cryptex Investigacion SA de CV
  • Guadalajara, Mexico, 44280
    • Recruiting
    • Hospital Civil de Guadalajara Fray Antonio Alcalde
  • Monterrey, Mexico, 64320
    • Recruiting
    • Consultorio del Dr. Joaquín Gabriel Reinoso Toledo
  • Monterrey, Mexico, 64460
    • Recruiting
    • Hospital Universitario "Dr Jose Eleuterio Gonzalez" Centro Universitario contra el Cáncer
  • Veracruz, Mexico, 91900
    • Recruiting
    • Sociedad de Metabolismo y Corazon S.C.
  • Yucatán, Mexico, 97134
    • Recruiting
    • Centro de Atencion e Investigacion Clinica en Oncologia (CAICO)
  • Region Chiapas
    • Tuxtla Gutiérrez, Region Chiapas, Mexico, 29038
      • Recruiting
      • Centro de Estudios y Prevención del Cáncer (CEPREC)
• Poland
  • Gdańsk, Poland, 80-214
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Gdynia, Poland, 81-519
    • Recruiting
    • Szpitale Pomorskie Sp.zo.o
  • Gliwice, Poland, 44-102
    • Recruiting
    • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie
  • Konin, Poland, 62-500
    • Recruiting
    • Przychodnia Lekarska KOMED Roman Karaszewski
  • Kraków, Poland, 30-510
    • Recruiting
    • Pratia CMC Kraków
  • Poznań, Poland, 60-185
    • Recruiting
    • Centrum Medyczne Pratia Poznan
  • Wrocław, Poland, 50-981
    • Recruiting
    • Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ
• Portugal
  • Braga, Portugal, 4710-243
    • Recruiting
    • Centro Clinico Academico
  • Coimbra, Portugal, 3000-075
    • Recruiting
    • Instituto Português de Oncologia de Coimbra Francisco Gentil, E.P.E.
  • Gaia, Portugal, 4434-502
    • Recruiting
    • Centro Hospitalar de Vila Nova de Gaia/Espinho
  • Lisboa, Portugal, 1649-028
    • Recruiting
    • Centro Hospitalar Universitário Lisboa Norte
  • Porto, Portugal, 4200-072
    • Recruiting
    • Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic Barcelona
  • Girona, Spain, 17007
    • Recruiting
    • Hospital Univ. Dr. Josep Trueta
  • Jaén, Spain, 23007
    • Recruiting
    • Complejo Hospitalario de Jaén
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28027
    • Recruiting
    • Clinica Universidad de Navarra - Madrid (CUN-M)
  • Majadahonda, Spain, 28222
    • Recruiting
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Malaga, Spain, 29010
    • Recruiting
    • Hospital Regional De Malaga
  • Palma de Mallorca, Spain, 07120
    • Recruiting
    • Hospital Universitario Son Espases
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Universidad de Navarra - Pamplona (CUN-P)
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital La Fe
  • Zaragoza, Spain, 50009
    • Recruiting
    • Hospital Miguel Servet
• Sweden
  • Goteborg, Sweden, 413 45
    • Recruiting
    • Sahlgrenska University Hospital
  • Lund, Sweden, 221 85
    • Recruiting
    • Skane University Hospital
  • Umeå, Sweden, 901 87
    • Recruiting
    • Norrlands University Hospital
• Taiwan
  • Changhua, Taiwan, 50006
    • Recruiting
    • Changhua Christian Hospital
  • Changhua, Taiwan, 50544
    • Recruiting
    • Chang Bing Show Chwan Memorial Hospital
  • Kaohsiung City, Taiwan, 80708
    • Recruiting
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 100225
    • Recruiting
    • National Taiwan University Hospital
• Turkey
  • Ankara, Turkey, 6230
    • Recruiting
    • Hacettepe University Cancer Institute
  • Edirne, Turkey, 22030
    • Recruiting
    • Trakya University
  • Istanbul, Turkey, 34214
    • Recruiting
    • Medipol Mega Universite Hastanesi
  • Istanbul, Turkey, 34098
    • Recruiting
    • Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty
  • Istanbul, Turkey, 34722
    • Recruiting
    • Istanbul Medeniyet University Medical Faculty
  • Malatya, Turkey, 44280
    • Recruiting
    • Inonu Universitesi - Turgut Ozal Tip Merkezi
  • İzmir, Turkey, 35575
    • Recruiting
    • Medical Park - Izmir Hastanesi
  • İzmir, Turkey, 35040
    • Recruiting
    • Ege Universitesi Tip Fakultesi Hastanesi - Tulay Aktas Onkoloji Hastanesi
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Recruiting
    • Beatson West of Scotland Cancer Centre
  • Liverpool, United Kingdom, L7 8YA
    • Recruiting
    • The Clatterbridge Cancer Centre
  • Oxford, United Kingdom, OX3 7LE
    • Recruiting
    • Oxford Cancer Centre
  • Southampton, United Kingdom, SO16 6YD
    • Recruiting
    • University Hospital Southampton NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • California Research Institute
    • Palo Alto, California, United States, 94304
      • Completed
      • Stanford Cancer Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Recruiting
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20052
      • Recruiting
      • The George Washington Cancer Center
  • Florida
    • Plantation, Florida, United States, 33324
      • Recruiting
      • University of Miami Miller School of Medicine
    • Plantation, Florida, United States, 33324-3274
      • Recruiting
      • University of Miami Miller School of Medicine
  • Georgia
    • Athens, Georgia, United States, 30607
      • Withdrawn
      • University Cancer and Blood Center
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Recruiting
      • Norton Cancer Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Recruiting
      • The University of New Mexico Comprehensive Cancer Center
  • New York
    • Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
  • Oregon
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Providence Cancer Institute
  • Washington
    • Tacoma, Washington, United States, 98405
      • Recruiting
      • MultiCare Regional Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Pre-screening phase (optional - patients can alternatively perform tumor biomarker testing as part of the main screening phase):

• Patients must sign the written pre-screening informed consent form (ICF) before any pre-screening procedures.
• Patients must have histologically confirmed recurrent or metastatic HNSCC with no prior systemic anticancer therapy administered in the recurrent or metastatic (R/M) setting.
• Patients have a clinical situation at a relatively high risk of developing R/M disease.
• Patients do not meet any exclusion criteria for the main clinical trial, except for time-dependent (e.g., prior systemic treatment in the prior 6 months) or potentially reversible conditions that in the opinion of the investigator will be resolved prior to potential enrollment into the main phase.

Main trial:

• Patients must sign the written informed consent form before any screening procedure. Informed consent must be documented before any trial-specific screening procedure is performed.
• Patients must be aged ≥18 years on the date of signing the informed consent.
• Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the trial.
• 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 approved test PD-L1 IHC 22C3 pharmDx kit performed and evaluated according to the manufacturer's specifications and relevant regulatory approvals.
• The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
• Patients must not have had prior systemic anticancer therapy administered in the incurable recurrent or metastatic setting. Systemic therapy which was completed more than 6 months 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.
• Patients have Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Patients have adequate bone marrow function as defined by hematological parameters.
• Patients have adequate hepatic function.
• Patients should have adequate kidney function, assessed by the estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m^2 using the Chronic Kidney Disease Epidemiology Collaboration (CPK-EPI) equation.
• Patients should be stable with adequate coagulation, as determined by the investigator.
• All patients must provide a tumor tissue sample (formalin fixed paraffin embedded [FFPE] blocks or both slides and curls) from archival tissue, or fresh biopsy if a biopsy is performed as part of the patient's standard clinical practice before the first dose of trial treatment.
• Women of childbearing potential (WOCBP) must not be pregnant. WOCBP, male patients who are sexually active with WOCBP and female partners of male patients should use a highly effective method of contraception up to at least 6 months after receiving the last dose of trial treatment, and should agree not to donate eggs (ova, oocytes) or sperm.

Exclusion Criteria:

Medical conditions:

• Patients are pregnant or breastfeeding.
• Patients present primary tumor site of nasopharynx (any histology).

• Patients with uncontrolled intercurrent illness, including but not limited to:

  • Ongoing or active infection which requires systemic treatment with antibiotics on the first dose of trial treatment.
  • Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), myocardial infarction within 3 months before screening, unstable angina pectoris, or cardiac arrhythmia.
  • Arterial thrombosis or pulmonary embolism within ≤6 months before the start of trial treatment, if not on a stable dose of anticoagulants or if in the opinion of the investigator contra-indicates trial inclusion.
  • Evidence or history of interstitial lung disease that, in the opinion of the investigator, is a contraindication for treatment with pembrolizumab, or active non-infectious pneumonitis.
  • Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management. Patients with arterial hypertension need to be on stable anti-hypertensive medication for at least 4 weeks prior to trial entry.
  • Known primary immunodeficiencies.
  • Evidence or history of significant autoimmune disease that (a) required treatment with systemic immunosuppressive treatments, (b) was associated with ongoing treatment with corticosteroids, or (c) was associated with a record of significant end-organ dysfunction (even if transient), which in the opinion of the investigator may suggest increased risk for immune-related AEs.
  • Patients with prior allogeneic stem cell or solid organ transplantation.
  • Any other disease, metabolic dysfunction, physical examination finding, and/or laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates the use of an investigational drug or may render the patient at high risk for complications.
• Patients with a known allergy, hypersensitivity, or intolerance to BNT113 or its excipients, or to pembrolizumab or its excipients.
• Patients who have had a splenectomy.
• Patients who have had major surgery (e.g., requiring general anesthesia) within 4 weeks before screening, or have not fully recovered from surgery, or have major surgery planned during the time of trial participation.

• Patients who have a known history or a positive test at screening of any of the following:

  1. Human immunodeficiency virus (HIV) 1 or 2. Inclusion is allowed if HIV 1/2 infection is adequately controlled and stable on a highly effective antiviral regimen.
  2. Hepatitis B infection, as defined by the presence of hepatitis B surface antigen (HbsAg) or hepatitis B virus (HBV) DNA positivity. Testing of HBV DNA is mandatory if hepatitis B core antibody is positive.
  3. Hepatitis C (unless considered cured).
• 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 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.

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 5 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 5 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 5 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.

Other comorbidities:

• Current evidence of Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade >1 toxicity before the start of treatment, except for hair loss and those Grade 2 toxicities listed as permitted in other eligibility criteria. Patients with Grade 2 neuropathy may be eligible at investigator's discretion.

• Current evidence of new or growing brain or spinal metastases during screening. Patients with known brain or spinal metastases may be eligible if they:

  1. had radiotherapy or another appropriate therapy for the brain or spinal metastases,
  2. have no neurological symptoms (excluding Grade ≤2 neuropathy),
  3. have no evidence of clinical or radiological progression within 4 weeks before signing the informed consent,
  4. do not require steroid therapy within 7 days before randomization or are undergoing slow steroid tapering, currently at doses ≤10 mg and neurologically stable.
  5. spinal bone metastases are allowed, unless imminent fracture or cord compression is anticipated.

Other exclusions:

• Patients who have previously been enrolled in this trial (rescreening is allowed once).
• Patients with substance abuse or known medical, psychological, or social conditions that in the opinion of the investigator may interfere with the patient's participation in the trial or evaluation of the trial results.
• Patients affiliated with the investigational site (e.g., a close relative of the investigator or dependent person, such as an employee or student of the trial site) or sponsor. For patients meeting this criterion, a prospective exception and eventual contingencies to be put in place may be defined on a case-by-case basis by the local Institutional Review Board.

Tumor-related conditions:

• Patients that have disease suitable for local therapy administered with curative intent.
• Patients that have a life expectancy of less than 3 months and/or have rapidly progressive disease, as assessed by the treating investigator.
• Patients with high-burden of visceral metastatic disease or location in anatomically critical areas (e.g., causing significant biliary or respiratory obstruction), that in the opinion of the investigator may benefit from treatment with chemotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A (Safety run-In) - BNT113 + Pembrolizumab; Safety Run-In Phase to confirm the safety and tolerability at the selected dose range level of BNT113 in combination with pembrolizumab.	Biological: Pembrolizumab; IV infusion; Biological: BNT113; IV injection
Experimental: Part B (Randomized phase) - BNT113 + Pembrolizumab; BNT113 in combination with pembrolizumab.	Biological: Pembrolizumab; IV infusion; Biological: BNT113; IV injection
Active Comparator: Part B (Randomized phase) - Pembrolizumab monotherapy; Pembrolizumab monotherapy.	Biological: Pembrolizumab; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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, fatal TEAE 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 - Overall response rate (ORR) assessed by blinded independent central review (BICR)	ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) (per response evaluation criteria in solid tumors [RECIST 1.1]) is observed as best overall response.	up to 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) by investigator's assessment	ORR defined as the proportion of patients in whom a CR or PR (per RECIST 1.1) is observed as best overall response.	up to 48 months
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.	up to 48 months
Part B - Progression free survival (PFS)	PFS defined as the time from randomization to the first objective tumor progression (per RECIST 1.1) or death from any cause, whichever occurs first.	up to 48 months
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) is observed as best overall response.	up to 48 months
Part B - Occurrence of TEAEs - BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy	TEAEs assessed according to CTCAE v5.0 including Grade ≥3, serious, fatal TEAE by relationship.	up to 27 months
Part B - Occurrence of dose reduction, delay, and discontinuation of trial treatments due to TEAEs	BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy.	up to 27 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported outcome (PRO) EORTC Quality of Life Questionnaire Core 30 (QLQ-C30)	PRO scores derived from the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire as change from baseline.	up to 48 months
PRO EORTC Quality of life - Head and Neck Cancer Module (QLQ-H&N35)	PRO scores derived from EORTC QLQ-H&N35 questionnaire as change from baseline.	up to 48 months
Time to deterioration in PRO scores EORTC QLQ-C30	Time to deterioration in PRO scores derived from EORTC QLQ-C30 questionnaire.	up to 48 months
Time to deterioration in PRO scores EORTC QLQ-H&N35	Time to deterioration in PRO scores derived from EORTC QLQ-H&N35 questionnaire.	up to 48 months

Collaborators and Investigators

• Sponsor: BioNTech SE
• Investigators: Study Director: BioNTech Responsible Person, BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2021
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): September 1, 2020

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Pembrolizumab; Metastatic; Unresectable; HNSCC; Head and neck cancer; HPV16; Cancer vaccine; mRNA vaccine; Recurrent; Head and neck; RNA vaccine; BNT113; HPV-positive
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Carcinoma; Recurrence; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Papilloma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: BNT113-01; 2020-001400-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No