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

Recurrent Head and Neck Cancer Clinical Trial

— AHEAD-MERIT  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04534205
• Other study ID #: BNT113-01
• Secondary ID: 2020-001400-41
• Status: Recruiting
• Phase: Phase 2
• Start date: January 7, 2021
• Est. completion date: May 2028

Study information

• Verified date: June 2024
• Source: BioNTech SE
• Contact: BioNTech clinical trials patient information
• Phone: +49 6131 9084
• Email: patients[@]biontech.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 285
• Est. completion date: May 2028
• Est. primary completion date: May 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Metastatic Head and Neck Cancer
• Papilloma
• Recurrence
• Recurrent Head and Neck Cancer
• Squamous Cell Carcinoma of Head and Neck
• Unresectable Head and Neck Squamous Cell Carcinoma

Intervention

Biological:
• BNT113
IV injection
• Pembrolizumab
IV infusion

Locations

Country	Name	City	State
Argentina	Centro de Oncología e Investigación Buenos Aires COIBA	Berazategui
Argentina	Hospital Britanico de Buenos Aires	Ciudad de Buenos Aires
Argentina	Instituto de Oncologia de Cordoba	Córdoba
Argentina	Centro Oncologico Riojano Integral	La Rioja
Argentina	Centro de Investigacion Pergamino SA - Clinica Pergamino	Pergamino
Argentina	Instituto de Oncologia de Rosario	Rosario
Argentina	Sanatorio Britanico	Rosario
Argentina	CAIPO Centro para la Atencion Integral del Paciente Oncologico	San Miguel De Tucumán
Argentina	Clinica Viedma	Viedma
Australia	Cancer Research SA	Adelaide
Australia	Bankstown-Lidcombe Hospital	Bankstown
Australia	Flinders Medical Centre	Bedford Park
Australia	Coffs Harbour Hospital	Coffs Harbour
Australia	St Vincent's Hospital	Fitzroy
Australia	Royal North Shore Hospital	Saint Leonards
Australia	John Flynn Private Hospital	Tugun
Australia	Southern Medical Day Care Centre	Wollongong
Austria	LKH - Univ. Klinikum Graz	Graz
Austria	Landeskrankenhaus/ Univ.-Kliniken Innsbruck	Innsbruck
Austria	HNO, Kopf-und Halschirurgie Ordensklinikum Linz Barmherzigen Schwestern	Linz
Austria	Uniklinikum Salzburg, Univ. Klinik fur Innere Medizin III	Salzburg
Belgium	Universitair Ziekenhuis Brussel	Bruxelles
Belgium	Universitair Ziekenhuis Gent UZ Gent	Gent
Belgium	CHR de la Citadelle	Liège
Brazil	Fundação PIO XII - Hospital de Amor Barretos	Barretos
Brazil	Fundacao Universidade de Caxias do Sul - Instituto de Pesquisas em Saude IPS-UCS	Caxias Do Sul
Brazil	Hospital Erasto Gaertner	Curitiba
Brazil	Hospial de Caridade de Ijui	Ijuí
Brazil	Hospital Marcio Cunha	Ipatinga
Brazil	Hospital Mae de Deus	Porto Alegre
Brazil	Hospital Sao Lucas da PUCRS	Porto Alegre
Brazil	Irmandade Santa Casa de Misericordia de Porto Alegre Hospital Santa Rita	Porto Alegre
Brazil	Instituto Nacional de Cancer Jose de Alencar Gomes da Silva - INCA	Rio De Janeiro
Brazil	Hospital Sao Rafael	Salvador
Brazil	Hospital de Base de Sao Jose do Rio Preto	São José Do Rio Preto
Brazil	Instituto do Cancer do Estado de São Paulo	São Paulo
Brazil	IBCC - Instituto Brasileiro de Controle do Cancer	Vila Mariana
Canada	Cross Cancer Institute	Edmonton
Canada	Jewish General Hospital	Montreal
Canada	McGill University Health Centre	Montréal
Canada	Princess Margaret Cancer Centre	Toronto
Chile	Centro de Estudios Clinicos SAGA	Santiago
Chile	Fundación Arturo López Pérez	Santiago
Chile	James Lind Centro de Investigación del Cáncer	Temuco
Czechia	Fakultni Nemocnice Olomouc	Olomouc
Czechia	Hospital Na Bulovce (Nemocnice na Bulovce)	Prague 8 - Liben
France	CHU de BORDEAUX, Hopital Saint Andre	Bordeaux
France	Centre Georges Francois Leclerc	Dijon Cedex
France	Clinique Victor Hugo	Le Mans
France	Hopital de la Timone	Marseille
France	Hopital Prive du Confluent	Nantes
France	Institut Curie	Paris
France	Institut Curie, Groupe Hospitalier Paris Saint-Joseph (GHPSJ)	Paris
France	CHU de Tours Hopital Bretonneau	Tours
Germany	Charite Universitätsklinikum Berlin - Campus Benjamin Franklin	Berlin
Germany	Krankenhaus Nordwest GmbH	Frankfurt am Main
Germany	Kath. Marien Krankenhaus gGmbH	Hamburg
Germany	SRH Wald-Klinikum Gera GmbH	Hamburg
Germany	Universitaetsklinik Heidelberg	Heidelberg
Germany	Klinik für HNO-Heilkunde, Kopf- und Hals-Chirurgie	Köln
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Klinikum rechts der Isar der TUM	München
Germany	Univeritätsklinikum Münster	Münster
Germany	Universitaetsmedizin Rostock - Medizinische Klink III (Hamatologie, Onkologie, Palliativmedizin)	Rostock
Germany	Caritas Klinikum Saarbrucken St. Theresia	Saarbruecken
Germany	Medizinische Universitaetsklinik Tuebingen	Tübingen
Germany	Universitaetsklinikum Wuerzburg	Würzburg
Hungary	Central Hospital of Northern Pest - Military Hospital	Budapest
Hungary	Uzsoki Utcai Korhaz Onkologiai Osztaly	Budapest
Hungary	DEKK Onkologiai Klinika	Debrecen
Hungary	Zala Megyei S. Rafael Korhaz	Zalaegerszeg
Italy	ASST Spedali Civili Brescia	Brescia
Italy	Mater Salutis Hospital AULSS 9 della Regione Veneto	Legnago
Italy	IRCCS Istituto Europeo di Oncologia	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Ospedale del Mare	Napoli
Italy	A.O.U. Maggiore della Carita	Novara
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte	Siena
Italy	Azienda Sanitaria Universitaria Integrata Friuli Centrale - Presidio ospedaliero di Udine	Udine
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Konyang University Hospital	Daejeon
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul ST. Mary's Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si
Korea, Republic of	The Catholic University of Korea St. Vincent's Hospital	Suwon-si
Mexico	Centro Estatal de Cancerologia de Chihuahua	Chihuahua
Mexico	Cryptex Investigacion SA de CV	Ciudad De México
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara
Mexico	Consultorio del Dr. Joaquín Gabriel Reinoso Toledo	Monterrey
Mexico	Hospital Universitario "Dr Jose Eleuterio Gonzalez" Centro Universitario contra el Cáncer	Monterrey
Mexico	Centro de Estudios y Prevención del Cáncer (CEPREC)	Tuxtla Gutiérrez	Region Chiapas
Mexico	Sociedad de Metabolismo y Corazón S.C.	Veracruz
Mexico	Centro de Atencion e Investigacion Clinica en Oncologia (CAICO)	Yucatán
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Szpitale Pomorskie Sp.zo.o	Gdynia
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie	Gliwice
Poland	Przychodnia Lekarska KOMED Roman Karaszewski	Konin
Poland	Pratia CMC Kraków	Kraków
Poland	Centrum Medyczne Pratia Poznan	Poznan
Poland	Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ	Wroclaw
Portugal	Centro Clinico Academico	Braga
Portugal	Instituto Português de Oncologia de Coimbra Francisco Gentil, E.P.E.	Coimbra
Portugal	Centro Hospitalar de Vila Nova de Gaia/Espinho	Gaia
Portugal	Centro Hospitalar Universitario Lisboa Norte	Lisboa
Portugal	Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E	Porto
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital Univ. Dr. Josep Trueta	Girona
Spain	Complejo Hospitalario de Jaen	Jaén
Spain	Clinica Universidad de Navarra - Madrid (CUN-M)	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda
Spain	Hospital Regional de Malaga	Malaga
Spain	Hospital Universitario Son Espases	Palma de Mallorca
Spain	Clinica Universidad de Navarra - Pamplona (CUN-P)	Pamplona
Spain	Hospital La Fe	Valencia
Spain	Hospital Miguel Servet	Zaragoza
Sweden	Sahlgrenska University Hospital	Goteborg
Sweden	Skane University Hospital	Lund
Sweden	Norrlands University Hospital	Umeå
Taiwan	Chang Bing Show Chwan Memorial Hospital	Changhua
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Chang Gung Memorial Hospital-Kaohsiung Branch	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung City
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Turkey	Medical Park Seyhan Hospital	Adana
Turkey	Hacettepe University Cancer Institute	Ankara
Turkey	Trakya University	Edirne
Turkey	Istanbul Medeniyet University Medical Faculty	Istanbul
Turkey	Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty	Istanbul
Turkey	Medipol Mega Universite Hastanesi	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Hastanesi - Tulay Aktas Onkoloji Hastanesi	Izmir
Turkey	Medical Park - Izmir Hastanesi	Izmir
Turkey	Inonu Universitesi - Turgut Ozal Tip Merkezi	Malatya
Turkey	Baskent University	Yüregir
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	The Clatterbridge Cancer Centre	Liverpool
United Kingdom	Oxford Cancer Centre	Oxford
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton
United States	The University of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico
United States	University Cancer and Blood Center	Athens	Georgia
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Tufts Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	California Research Institute	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Yale University	New Haven	Connecticut
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Stanford Cancer Institute	Palo Alto	California
United States	University of Miami Miller School of Medicine	Plantation	Florida
United States	University of Miami Miller School of Medicine	Plantation	Florida
United States	Providence Cancer Institute	Portland	Oregon
United States	MultiCare Regional Cancer Center	Tacoma	Washington
United States	The George Washington Cancer Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
BioNTech SE

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Czechia,  France,  Germany,  Hungary,  Italy,  Korea, Republic of,  Mexico,  Poland,  Portugal,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Primary	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
Primary	Part B - Overall Survival (OS)	OS defined as the time from randomization to death from any cause.	up to 48 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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