Clinical trial NCT04534205: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Unresectable Head and Neck Squamous Cell Carcinoma
Metastatic Head and Neck Cancer
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
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
First posted: 2020-09-01
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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.

Primary outcomes:
measure: Part A - Occurrence of treatment-emergent adverse event (TEAE) - BNT113 in combination with pembrolizumab
timeFrame: up to 27 months
measure: Part B - Overall survival (OS)
timeFrame: up to 48 months
measure: Part B - Progression-free survival (PFS)
timeFrame: up to 48 months
Secondary outcomes:
measure: Part A and B - Overall response rate (ORR)
timeFrame: up to 48 months
measure: Part A and B - Duration of response (DOR)
timeFrame: up to 48 months
measure: Part A - Disease control rate (DCR)
timeFrame: up to 48 months
measure: Part B - Progression free survival (PFS)
timeFrame: up to 48 months
measure: Part B - PFS rate at 6 months
timeFrame: from randomization until 6 months after randomization
measure: Part B - PFS rate at 12 months
timeFrame: from randomization until 12 months after randomization
measure: Part B - Occurrence of TEAEs - BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy
timeFrame: up to 27 months
measure: Part B - Occurrence of dose reduction, delay, and discontinuation of trial treatments due to TEAEs
timeFrame: up to 27 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: California Research Institute
state: California
city: Los Angeles
country: United States
facility: UCLA Cancer Care
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: The George Washington Cancer Center
state: District of Columbia
city: Plantation
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Plantation
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Athens
country: United States
facility: University Cancer and Blood Center
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Albuquerque
country: United States
facility: The University of New Mexico Comprehensive Cancer Center
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Center
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Tacoma
country: United States
facility: MultiCare Regional Cancer Center
state: Washington
city: Berazategui
country: Argentina
facility: Centro de Oncología e Investigación Buenos Aires COIBA
city: Ciudad de Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Córdoba
country: Argentina
facility: Instituto de Oncologia de Cordoba
city: La Rioja
country: Argentina
facility: Centro Oncologico Riojano Integral
city: Pergamino
country: Argentina
facility: Centro de Investigacion Pergamino SA - Clinica Pergamino
city: Rosario
country: Argentina
facility: Instituto de Oncologia de Rosario
city: Rosario
country: Argentina
facility: Sanatorio Britanico
city: San Miguel De Tucumán
country: Argentina
facility: CAIPO Centro para la Atencion Integral del Paciente Oncologico
city: Viedma
country: Argentina
facility: Clinica Viedma
city: Adelaide
country: Australia
facility: Cancer Research SA
city: Bankstown
country: Australia
facility: Bankstown-Lidcombe Hospital
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Coffs Harbour
country: Australia
facility: Coffs Harbour Hospital
city: Fitzroy
country: Australia
facility: St Vincent's Hospital
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
city: Tugun
country: Australia
facility: John Flynn Private Hospital
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
city: Graz
country: Austria
facility: LKH - Univ. Klinikum Graz
city: Innsbruck
country: Austria
facility: Landeskrankenhaus/ Univ.-Kliniken Innsbruck
city: Linz
country: Austria
facility: HNO, Kopf-und Halschirurgie Ordensklinikum Linz Barmherzigen Schwestern
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg, Univ. Klinik fur Innere Medizin III
city: Bruxelles
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent UZ Gent
city: Liège
country: Belgium
facility: CHR de la Citadelle
city: Barretos
country: Brazil
facility: Fundação PIO XII - Hospital de Amor Barretos
city: Caxias Do Sul
country: Brazil
facility: Fundacao Universidade de Caxias do Sul - Instituto de Pesquisas em Saude IPS-UCS
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
city: Ijuí
country: Brazil
facility: Oncosite - Centro de Pesquisa Clinica em Oncologia
city: Ipatinga
country: Brazil
facility: Hospital Marcio Cunha
city: Porto Alegre
country: Brazil
facility: Irmandade Santa Casa de Misericordia de Porto Alegre Hospital Santa Rita
city: Porto Alegre
country: Brazil
facility: Hospital Mae de Deus
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUCRS
city: Rio De Janeiro
country: Brazil
facility: Instituto Nacional de Cancer Jose de Alencar Gomes da Silva - INCA
city: Salvador
country: Brazil
facility: Hospital Sao Rafael
city: São José Do Rio Preto
country: Brazil
facility: Hospital de Base de Sao Jose do Rio Preto
city: São Paulo
country: Brazil
facility: Instituto do Cancer do Estado de São Paulo
city: Vila Mariana
country: Brazil
facility: IBCC - Instituto Brasileiro de Controle do Cancer
city: Edmonton
country: Canada
facility: Cross Cancer Institute
city: Kelowna
country: Canada
facility: British Columbia Cancer Agency
city: Montreal
country: Canada
facility: Jewish General Hospital
city: Montréal
country: Canada
facility: McGill University Health Centre
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: Santiago
country: Chile
facility: Centro de Estudios Clinicos SAGA
city: Santiago
country: Chile
facility: Fundación Arturo López Pérez
city: Temuco
country: Chile
facility: James Lind Centro de Investigación del Cáncer
city: Olomouc
country: Czechia
facility: Fakultni Nemocnice Olomouc
city: Prague 8 - Liben
country: Czechia
facility: Hospital Na Bulovce (Nemocnice na Bulovce)
city: Bordeaux
country: France
facility: CHU de BORDEAUX, Hopital Saint Andre
city: Caen
country: France
facility: CHU de Caen Normandie
city: Dijon Cedex
country: France
facility: Centre Georges Francois Leclerc
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Levallois-Perret
country: France
facility: Institut de Radiothérapie Hartmann, GCS CCConcorde
city: Marseille
country: France
facility: Hopital de la Timone
city: Nantes
country: France
facility: Hopital Prive du Confluent
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Institut Curie, Groupe Hospitalier Paris Saint-Joseph (GHPSJ)
city: Tours
country: France
facility: CHU de Tours Hopital Bretonneau
city: Villejuif
country: France
facility: Hospital Gustave Roussy
city: Berlin
country: Germany
facility: Charite Universitätsklinikum Berlin - Campus Benjamin Franklin
city: Frankfurt am Main
country: Germany
facility: Krankenhaus Nordwest GmbH
city: Hamburg
country: Germany
facility: SRH Wald-Klinikum Gera GmbH
city: Hamburg
country: Germany
facility: Kath. Marien Krankenhaus gGmbH
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover (MHH)
city: Heidelberg
country: Germany
facility: Universitaetsklinik Heidelberg
city: Köln
country: Germany
facility: Klinik für HNO-Heilkunde, Kopf- und Hals-Chirurgie
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Mainz
country: Germany
facility: UNIVERSITAETSMEDIZIN der Johannes Gutenberg-Universitaet Mainz
city: München
country: Germany
facility: Klinikum rechts der Isar der TUM
city: Münster
country: Germany
facility: Univeritätsklinikum Münster
city: Rostock
country: Germany
facility: Universitaetsmedizin Rostock - Medizinische Klink III (Hamatologie, Onkologie, Palliativmedizin)
city: Saarbruecken
country: Germany
facility: Caritas Klinikum Saarbrucken St. Theresia
city: Tübingen
country: Germany
facility: Medizinische Universitaetsklinik Tuebingen
city: Würzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Budapest
country: Hungary
facility: Central Hospital of Northern Pest - Military Hospital
city: Budapest
country: Hungary
facility: Uzsoki Utcai Korhaz Onkologiai Osztaly
city: Debrecen
country: Hungary
facility: DEKK Onkologiai Klinika
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei S. Rafael Korhaz
city: Haifa
country: Israel
facility: Rambam Health Clinical
city: Jerusalem
country: Israel
facility: Hadassah Medical Center - Sharett Institute of Oncology
city: Petah tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Brescia
country: Italy
facility: ASST Spedali Civili Brescia
city: Legnago
country: Italy
facility: Mater Salutis Hospital AULSS 9 della Regione Veneto
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Milano
country: Italy
facility: IRCCS Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Ospedale del Mare
city: Novara
country: Italy
facility: A.O.U. Maggiore della Carita
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata Friuli Centrale - Presidio ospedaliero di Udine
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Konyang University Hospital
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul ST. Mary's Hospital
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea St. Vincent's Hospital
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
city: Tuxtla Gutiérrez
country: Mexico
facility: Centro de Estudios y Prevención del Cáncer (CEPREC)
state: Region Chiapas
city: Chihuahua
country: Mexico
facility: Centro Estatal de Cancerologia de Chihuahua
city: Ciudad De México
country: Mexico
facility: Cryptex Investigacion SA de CV
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Fray Antonio Alcalde
city: Monterrey
country: Mexico
facility: Consultorio del Dr. Joaquín Gabriel Reinoso Toledo
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr Jose Eleuterio Gonzalez" Centro Universitario contra el Cáncer
city: Oaxaca de Juarez
country: Mexico
facility: Oaxaca Site Management Organization S. C.
city: Veracruz
country: Mexico
facility: Sociedad de Metabolismo y Corazón S.C.
city: Yucatán
country: Mexico
facility: Centro de Atencion e Investigacion Clinica en Oncologia (CAICO)
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp.zo.o
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED Roman Karaszewski
city: Kraków
country: Poland
facility: MCM Pratia Krakow
city: Poznań
country: Poland
facility: Centrum Medyczne Pratia Poznań
city: Wrocław
country: Poland
facility: Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ
city: Braga
country: Portugal
facility: Centro Clinico Academico
city: Coimbra
country: Portugal
facility: Instituto Português de Oncologia de Coimbra Francisco Gentil, E.P.E.
city: Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia/Espinho
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitario Lisboa Norte
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Girona
country: Spain
facility: Hospital Univ. Dr. Josep Trueta
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaen
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra - Madrid (CUN-M)
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Malaga
country: Spain
facility: Hospital Regional de Malaga
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Espases
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona (CUN-P)
city: Valencia
country: Spain
facility: Hospital La Fe
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
city: Goteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Skane University Hospital
city: Umeå
country: Sweden
facility: Norrlands University Hospital
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Changhua
country: Taiwan
facility: Chang Bing Show Chwan Memorial Hospital
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital-Kaohsiung Branch
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Adana
country: Turkey
facility: Medical Park Seyhan Hospital
city: Ankara
country: Turkey
facility: Ankara Bilkent Sehir Hastanesi
city: Ankara
country: Turkey
facility: Hacettepe University Cancer Institute
city: Edirne
country: Turkey
facility: Trakya University
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Onkoloji Enstitusu
city: Istanbul
country: Turkey
facility: Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Medipol Mega Universite Hastanesi
city: Istanbul
country: Turkey
facility: Istanbul Medeniyet University Medical Faculty
city: İzmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi Hastanesi - Tulay Aktas Onkoloji Hastanesi
city: İzmir
country: Turkey
facility: Medical Park - Izmir Hastanesi
city: Malatya
country: Turkey
facility: Inonu Universitesi - Turgut Ozal Tip Merkezi
city: Yüreğir
country: Turkey
facility: Baskent University
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham, Queen Elizabeth Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust (St James's University Hospital)
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre
city: London
country: United Kingdom
facility: University College London Hospitals
city: London
country: United Kingdom
facility: Guy's Cancer Centre, Guy's Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospital NHS Foundation Trust - Fulham Road
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford Cancer Centre
city: Preston
country: United Kingdom
facility: Royal Preston Hospital Lancashire Teaching Hospitals NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
city: Stevenage
country: United Kingdom
facility: Mount Vernon Cancer Centre, East and North Hertfordshire NHS Trust
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital - Sutton
Study officials:
affiliation: BioNTech SE
name: BioNTech Responsible Person
role: STUDY_DIRECTOR
References: