Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer

NCT ID: NCT05142189

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

280 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-17

Study Completion Date

2031-11-30

Brief Summary

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This first-in-human (FIH) trial for BNT116 aims to establish the safety profile and a safe dose for BNT116 monotherapy as well as for BNT116 in combination with approved medicinal products and/or in combination with investigational medicinal products (IMPs) including, but not limited to, cemiplimab, docetaxel, carboplatin, paclitaxel, BNT316 (an anti-cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\] antibody), an anti-B7-H3 antibody conjugated to a topoisomerase I inhibitor, an anti-human epidermal growth factor receptor 3 (HER3) antibody conjugated to a topoisomerase I inhibitor or a bispecific antibody for programmed death ligand 1 (PD-L1) and vascular endothelial growth factor A (VEGF-A) in participants with non-small cell lung cancer (NSCLC).

The trial will comprise of several cohorts for dose confirmation in monotherapy as well as in combinations of BNT116 as mentioned above.

The trial will enroll participants with NSCLC in advanced or metastatic stage in Cohorts 1 to 4 and Cohorts 7 to 10, unresectable NSCLC Stage III in Cohorts 5 and 11, and resectable NSCLC of Stage II and III in Cohort 6.

Detailed Description

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The maximum duration of treatment for each individual participant in this trial is:

* Cohorts 1 to 4, and Cohorts 7 to 10: 24 months
* Cohorts 5 and 11: 18 cycles, i.e., 12 months
* Cohort 6: 4 cycles of neo-adjuvant treatment and 18 cycles of adjuvant treatment, i.e., 12 months of adjuvant treatment

Conditions

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Non-Small Cell Lung Cancer

Keywords

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Cancer Vaccine Non-Small Cell Lung Cancer Combination with chemotherapy Combination with other investigational agents anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] antibody anti-B7-H3 antibody conjugated to topoisomerase I inhibitor anti-HER3 antibody conjugated to topoisomerase I inhibitor Immunotherapy Antibody-drug conjugate (ADC) Combination with a PD-1 inhibitor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 11: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (After Concurrent CRT)

Dose confirmation for BNT116 in combination with a bispecific antibody for PD-L1 and VEGF-A will be established in participants after concurrent CRT.

Group Type EXPERIMENTAL

BNT116

Intervention Type BIOLOGICAL

Intravenous injection

Bispecific antibody for PD-L1 and VEGF-A

Intervention Type BIOLOGICAL

Intravenous infusion

Cohort 1A - BNT116 Monotherapy

Group Type EXPERIMENTAL

BNT116

Intervention Type BIOLOGICAL

Intravenous injection

Cohort 1B - BNT116 Monotherapy

Group Type EXPERIMENTAL

BNT116

Intervention Type BIOLOGICAL

Intravenous injection

Cohort 2 - BNT116 + Cemiplimab (PD-1/PD-L1 Inhibitor Refractory/Relapsed Participants)

Group Type EXPERIMENTAL

BNT116

Intervention Type BIOLOGICAL

Intravenous injection

Cemiplimab

Intervention Type BIOLOGICAL

Intravenous infusion

Cohort 3 - BNT116 + Docetaxel

Group Type EXPERIMENTAL

BNT116

Intervention Type BIOLOGICAL

Intravenous injection

Docetaxel

Intervention Type DRUG

Intravenous infusion

Cohort 4 - BNT116 + Cemiplimab (Frail Participants)

Group Type EXPERIMENTAL

BNT116

Intervention Type BIOLOGICAL

Intravenous injection

Cemiplimab

Intervention Type BIOLOGICAL

Intravenous infusion

Cohort 5 - BNT116 + Cemiplimab (After Concurrent Chemoradiotherapy [CRT])

Group Type EXPERIMENTAL

BNT116

Intervention Type BIOLOGICAL

Intravenous injection

Cemiplimab

Intervention Type BIOLOGICAL

Intravenous infusion

Cohort 6 - BNT116 + Cemiplimab + Carboplatin + Paclitaxel

BNT116 + cemiplimab + carboplatin + paclitaxel as neo-adjuvant treatment followed by surgery, thereafter adjuvant treatment with BNT116 + cemiplimab

Group Type EXPERIMENTAL

BNT116

Intervention Type BIOLOGICAL

Intravenous injection

Cemiplimab

Intervention Type BIOLOGICAL

Intravenous infusion

Carboplatin

Intervention Type DRUG

Intravenous infusion

Paclitaxel

Intervention Type DRUG

Intravenous infusion

Cohort 7 - BNT116 + BNT316

Dose finding for the combination of BNT116 with BNT316 (CTLA4 antibody) with dose escalation of BNT316

Group Type EXPERIMENTAL

BNT116

Intervention Type BIOLOGICAL

Intravenous injection

BNT316

Intervention Type BIOLOGICAL

Intravenous infusion

Cohort 8: BNT116 + Anti-B7-H3 Antibody Conjugated to Topoisomerase I Inhibitor

Dose finding for the combination of BNT116 with an anti-B7-H3 antibody conjugated to a topoisomerase I inhibitor with dose escalation of the anti-B7-H3 antibody conjugated to a topoisomerase I inhibitor

Group Type EXPERIMENTAL

BNT116

Intervention Type BIOLOGICAL

Intravenous injection

anti-B7-H3 antibody conjugated to topoisomerase I inhibitor

Intervention Type BIOLOGICAL

Intravenous infusion

Cohort 9: BNT116 + Anti-HER3 Antibody Conjugated to Topoisomerase I Inhibitor

Dose confirmation for the combination of BNT116 with an anti-HER3 antibody conjugated to a topoisomerase I inhibitor with dose escalation of the anti-HER3 antibody conjugated to a topoisomerase I inhibitor

Group Type EXPERIMENTAL

BNT116

Intervention Type BIOLOGICAL

Intravenous injection

anti-HER3 antibody conjugated to topoisomerase I inhibitor

Intervention Type BIOLOGICAL

Intravenous infusion

Cohort 10: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (Frail Participants)

Dose confirmation for BNT116 in combination with a bispecific antibody for programmed death ligand 1 (PD-L1) and vascular endothelial growth factor A (VEGF-A) will be established.

Group Type EXPERIMENTAL

BNT116

Intervention Type BIOLOGICAL

Intravenous injection

Bispecific antibody for PD-L1 and VEGF-A

Intervention Type BIOLOGICAL

Intravenous infusion

Interventions

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BNT116

Intravenous injection

Intervention Type BIOLOGICAL

Cemiplimab

Intravenous infusion

Intervention Type BIOLOGICAL

Docetaxel

Intravenous infusion

Intervention Type DRUG

Carboplatin

Intravenous infusion

Intervention Type DRUG

Paclitaxel

Intravenous infusion

Intervention Type DRUG

BNT316

Intravenous infusion

Intervention Type BIOLOGICAL

anti-B7-H3 antibody conjugated to topoisomerase I inhibitor

Intravenous infusion

Intervention Type BIOLOGICAL

anti-HER3 antibody conjugated to topoisomerase I inhibitor

Intravenous infusion

Intervention Type BIOLOGICAL

Bispecific antibody for PD-L1 and VEGF-A

Intravenous infusion

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Participants must have histologically confirmed NSCLC and measurable disease by RECIST v1.1. Note: Participants in Cohorts 1, 5 and 11 do not have to present with measurable disease.

1. Participants must present with unresectable Stage III or metastatic Stage IV NSCLC by American Joint Commission on Cancer (AJCC) Cancer Staging Manual, Eighth Edition.

EXCEPT
2. Participants in Cohorts 5 and 11 must present with unresectable Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition before receiving pre-trial chemoradiotherapy.
3. Participants in Cohort 6 with the initial diagnosis of resectable Stage II and Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition.
* Participants in Cohorts 2, 4, 5, 6, 10 and 11 must be able to tolerate (additional) anti-PD-1 therapy (i.e., did not permanently discontinue anti-programmed death protein 1 \[PD-1\] / programmed death ligand 1 \[PD-L1\] therapy due to toxicity).
* Participants must have an Eastern Cooperative Oncology Group performance status (ECOG-PS) less than or equal to (\<=) 1, except for participants in Cohorts 1, 4, 5, 10 and 11 who are eligible with an ECOG-PS of 0-2.


Cohort 1:

* Participants prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen as well as one other line of systemic therapy (except if a participant is not candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor and/or another line of systemic therapy). Note: Participants newly enrolled in Cohort 1B under protocol v 5.0 and subsequent versions of the protocol must consent to mandatory blood sampling for peripheral blood mononuclear cells (PBMCs).
* Participants who are to start cemiplimab at Cycle 3 must present with PD-L1 expression of tumor proportion score (TPS) greater than or equal to (\>=) 1% in tumor cells (as determined locally).

Cohort 2:

* Participants must present with PD-L1 expression of tumor proportion score (TPS) \>= 50% in tumor cells (as determined locally prior to inclusion in this trial).
* Participants must present with progressive disease either

1. in the advanced or metastasized stage of NSCLC: while on a PD-1/PD-L1 inhibitor therapy or within 6 months of termination of this treatment as first-line treatment. Or
2. be refractory to ongoing adjuvant therapy/maintenance treatment after CRT with a PD-1/PD-L1 inhibitor that has been given for at least 3 months in monotherapy (i.e., after an initial combination therapy) before being enrolled into this trial.

Cohort 3:

* Participants prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a participant is not candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor).
* Participants must present with progressive disease.

Cohort 4:

* Participants who are not candidates for chemotherapy as first-line treatment for the advanced or metastasized stage of NSCLC may be enrolled if presenting with PD-L1 expression: TPS \>= 1% in tumor cells (as determined locally).

Cohort 5:

* Participants NSCLC must have been considered unresectable due to participant's condition and/or tumor-related factors and the participants must have undergone chemoradiotherapy before entering the trial.

Cohort 6:

* Participants NSCLC must be considered technically and medically resectable.
* Participants must be considered eligible for neo-adjuvant treatment.

Cohort 7:

* Participants prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a participant is not a candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor). Note 1: Participants may have received prior therapy targeting CTLA-4, lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif \[ITIM\] domain (TIGIT), VEGF or VEGF receptor (VEGFR) inhibitor as monotherapy or part of a combination therapy. Note 2: If the participants' prior therapies included a CTLA-4 inhibitor, the participant must be able to tolerate (additional) treatment with the CTLA-4 inhibitor.
* Participants must present with progressive disease at trial enrollment.
* Participants must consent to mandatory blood sampling for PBMCs.

Cohorts 8 \& 9:

* Participants prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a participant is not a candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor).
* Participants must present with progressive disease at trial enrollment.

Cohort 10:

* Participants who are not candidates for chemotherapy as first-line treatment for the advanced or metastasized stage of NSCLC may be enrolled.

Cohort 11:

* Participant's NSCLC must have been considered unresectable due to participants condition and/or tumor related factors and the participants must have undergone chemoradiotherapy before entering the trial.

Exclusion Criteria

* Ongoing active systemic treatment against NSCLC.
* Presence of a driver mutation for which approved target therapies are available except if the participant is not a candidate for the respective targeted therapy.
* Ongoing or recent evidence (within the last 5 years) of significant autoimmune disease that required treatment with systemic immunosuppressive treatments which may suggest risk for immune-related adverse events. Note: Participants with autoimmune-related hyperthyroidism, autoimmune-related hypothyroidism who are in remission, or on a stable dose of thyroid-replacement hormone, vitiligo, or psoriasis may be included.
* Current evidence of new or growing brain or spinal metastases during screening. Participants with leptomeningeal disease are excluded. Participants with known brain or spinal metastases may be eligible for all Cohorts, except for Cohorts 5, 6 and 11, if they:
* had radiotherapy or another appropriate therapy for the brain or spinal metastases, AND
* have no neurological symptoms that can be attributed to the current brain lesions, AND
* have stable brain or spinal disease on the computed tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the informed consent (confirmed by stable lesions on two scans at least 4 weeks apart), AND
* do not require steroid therapy for the treatment of brain or spinal metastases within 14 d before the first dose of trial treatment. Note: Spinal bone metastases (that is, of the vertebrae) are allowed, unless imminent fracture or cord compression is anticipated.
* Systemic immune suppression:
* Current use of chronic systemic steroid medication (\<= 5 mg/day prednisolone equivalent is allowed); participants using physiological replacement doses of prednisone for adrenal or pituitary insufficiency are eligible. Note: Steroid medication given for supportive or prophylactic reasons during CRT for participants in Cohorts 5 and 11 needs to be tapered to \<= 5 mg/day prednisolone equivalent at latest on the day before the trial treatment starts.
* Other clinically relevant systemic immune suppression within the last 3 months before trial enrollment.
* Known history of seropositivity for human immunodeficiency virus (HIV) with CD4+ T-cell (CD4+) counts less than (\<) 350 cells/microlitre (mcL) and with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections.
* Prior splenectomy.
* History/risk of interstitial lung disease or low baseline lung function (baseline pulse oximetry of less than 92% oxygen saturation \[SpO2\] without additional oxygen).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BioNTech SE

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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BioNTech Responsible Person

Role: STUDY_DIRECTOR

BioNTech SE

Locations

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University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States

Site Status RECRUITING

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status RECRUITING

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

NEXT Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

Scientia Clinical Research

Randwick, New South Wales, Australia

Site Status RECRUITING

Royal North Shore Hospital

Sydney, New South Wales, Australia

Site Status RECRUITING

Cancer Research SA

Adelaide, South Australia, Australia

Site Status RECRUITING

Monash Health

Clayton, Victoria, Australia

Site Status RECRUITING

Universitätsklinikum Köln

Cologne, , Germany

Site Status RECRUITING

Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)

Frankfurt, , Germany

Site Status RECRUITING

University Medical Center Hamburg-Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR

Mainz, , Germany

Site Status RECRUITING

ICON-PRA Budapest, Fázis 1 Vizsgálóhely

Budapest, , Hungary

Site Status COMPLETED

Semmelweis Egyetem ÁOK Belgyógyászati és Onkológiai Klinika

Budapest, , Hungary

Site Status RECRUITING

National Institute of Oncology

Budapest, , Hungary

Site Status RECRUITING

Clinexpert Ltd

Gyöngyös, , Hungary

Site Status RECRUITING

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Site Status RECRUITING

Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie

Olsztyn, , Poland

Site Status RECRUITING

NZOZ Medpolonia Sp. Z o.o

Poznan, , Poland

Site Status RECRUITING

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Warsaw, , Poland

Site Status WITHDRAWN

Institut Catala d'Oncologia Badalona, Hospital Germans Trias I Pujol

Badalona, , Spain

Site Status RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

MD Anderson Cancer Center

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Site Status RECRUITING

START Madrid - CIOCC. Grupo Hospital de Madrid (HM) - Centro Integral Oncologico Clara Campal (CIOCC)

Madrid, , Spain

Site Status RECRUITING

Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) - Hospital Clinico Universitario (University Clinical Hospital)

Santiago de Compostela, , Spain

Site Status RECRUITING

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status RECRUITING

Hospital Universitario y Politecnico La Fe

Valencia, , Spain

Site Status RECRUITING

Adana Sehir Hospital

Adana, , Turkey (Türkiye)

Site Status NOT_YET_RECRUITING

Haceteppe Hospital

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Ankara City Hospital

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Koc University Hospital

Istanbul, , Turkey (Türkiye)

Site Status RECRUITING

University Medical Faculty Oncology Institute

Istanbul, , Turkey (Türkiye)

Site Status NOT_YET_RECRUITING

Yeditepe University

Istanbul, , Turkey (Türkiye)

Site Status RECRUITING

Ege University School of Medicine Tulay Aktas Oncology Hospital

Izmir, , Turkey (Türkiye)

Site Status RECRUITING

Dokuz Eylul Medical School

Izmir, , Turkey (Türkiye)

Site Status COMPLETED

Adana Sehir Hospital

Yüreğir, , Turkey (Türkiye)

Site Status RECRUITING

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Site Status RECRUITING

Velindre NHS Trust

Cardiff, , United Kingdom

Site Status RECRUITING

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, , United Kingdom

Site Status RECRUITING

Guy's and St Thomas NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Germany Hungary Poland Spain Turkey (Türkiye) United Kingdom

Central Contacts

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BioNTech clinical trials patient information

Role: CONTACT

Phone: +49 6131 9084

Email: [email protected]

Other Identifiers

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2021-004739-94

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-509283-14-00

Identifier Type: CTIS

Identifier Source: secondary_id

BNT116-01

Identifier Type: -

Identifier Source: org_study_id