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

NCT05142189 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: BNT116-012021-004739-942023-509283-14-00
• Study Type: interventional
• Target: 320
• Locations: 8 countries
• Sites: 45

Brief Summary

This first-in-human (FIH) study 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, osimertinib, anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), rearranged during transfection (RET) TKIs, 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 study will comprise several cohorts for dose confirmation in monotherapy as well as in combinations of BNT116 as mentioned above. The study 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, resectable NSCLC of Stage II and III in Cohort 6, advanced/metastatic epidermal growth factor receptor (EGFR)-mutant NSCLC in Cohort EGFR, and advanced/metastatic ALK rearranged or RET rearranged NSCLC in Cohort ALK/RET. Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.

Conditions

Non-Small Cell Lung Cancer

Keywords

Cancer Vaccine; Non-Small Cell Lung Cancer; Combination with chemotherapy; Combination with other investigational agents; anti-B7-H3 antibody conjugated to topoisomerase I inhibitor; anti-HER3 antibody conjugated to topoisomerase I inhibitor; Immunotherapy; Antibody-drug conjugate (ADC); Anaplastic lymphoma kinase (ALK) rearranged Non-Small Cell Lung Cancer; Rearranged during transfection (RET) rearranged Non-Small Cell Lung Cancer; NSCLC; anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody; Epidermal growth factor receptor (EGFR)-mutant Non-Small Cell Lung Cancer; Combination with a programmed cell death protein 1 (PD-1) inhibitor; Human epidermal growth factor receptor 3

Outcome Measures

Primary Outcomes (4)

• Cohorts 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, EGFR and ALK/RET: Occurrence of Dose-Limiting Toxicities (DLTs) During the DLT Observation Period

  Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.

  From first dose of IMP up to 21 days

• Cohorts 1 to 11, EGFR and ALK/RET: Occurrence of Treatment-Emergent Adverse Events (TEAEs) Reported by Relationship, Seriousness, and Grade

  According to National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0). Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.

  up to 27 months

• Cohort 6 only: Occurrence of Post-Surgical Adverse Events (AEs) Related to BNT116 and Cemiplimab

  up to 27 months

• Cohort 6 only: Occurrence of Treatment-Related Delays to Surgery More Than 9 weeks Post the Last Dose of Neo-Adjuvant Treatment

  up to 6 months

Secondary Outcomes (14)

• Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Overall Response Rate (ORR)

  up to 27 months

• Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Response (DoR)

  up to 27 months

• Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Disease Control Rate (DCR)

  up to 27 months

• Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Disease Control

  up to 27 months

• Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Progression-Free Survival (PFS)

  up to 48 months

Study Arms (14)

Cohort 1A - BNT116 Monotherapy

EXPERIMENTAL

Biological: BNT116

Cohort 1B - BNT116 Monotherapy

EXPERIMENTAL

Biological: BNT116

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

EXPERIMENTAL

Biological: BNT116; Biological: Cemiplimab

Cohort 3 - BNT116 + Docetaxel

EXPERIMENTAL

Biological: BNT116; Drug: Docetaxel

Cohort 4 - BNT116 + Cemiplimab (Frail Participants)

EXPERIMENTAL

Biological: BNT116; Biological: Cemiplimab

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

EXPERIMENTAL

Biological: BNT116; Biological: Cemiplimab

Cohort 6 - BNT116 + Cemiplimab + Carboplatin + Paclitaxel

EXPERIMENTAL

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

Biological: BNT116; Biological: Cemiplimab; Drug: Carboplatin; Drug: Paclitaxel

Cohort 7 - BNT116 + BNT316

EXPERIMENTAL

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

Biological: BNT116; Biological: BNT316

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

EXPERIMENTAL

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

Biological: BNT116; Biological: anti-B7-H3 antibody conjugated to topoisomerase I inhibitor

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

EXPERIMENTAL

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

Biological: BNT116; Biological: anti-HER3 antibody conjugated to topoisomerase I inhibitor

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

EXPERIMENTAL

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.

Biological: BNT116; Biological: Bispecific antibody for PD-L1 and VEGF-A

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

EXPERIMENTAL

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

Biological: BNT116; Biological: Bispecific antibody for PD-L1 and VEGF-A

Cohort EGFR : BNT116 + osimertinib

EXPERIMENTAL

Dose confirmation for BNT116 in combination with ongoing osimertinib therapy. Treatment with osimertinib is standard of care. Cohort will enroll only at selected sites in the US.

Biological: BNT116; Biological: Osimertinib

Cohort ALK/RET: BNT116 + ALK TKI or RET TKI

EXPERIMENTAL

Dose confirmation for BNT116 in combination with either ongoing ALK-inhibitor or ongoing RET-inhibitor therapy. Treatment with ALK TKI or RET TKI is standard of care. Cohort will enroll only at selected sites in the US.

Biological: BNT116; Biological: ALK-inhibitor or RET-inhibitor

Interventions

Osimertinib BIOLOGICAL

Oral

Cohort EGFR : BNT116 + osimertinib

ALK-inhibitor or RET-inhibitor BIOLOGICAL

Oral

Cohort ALK/RET: BNT116 + ALK TKI or RET TKI

Docetaxel DRUG

Intravenous infusion

Cohort 3 - BNT116 + Docetaxel

Carboplatin DRUG

Intravenous infusion

Cohort 6 - BNT116 + Cemiplimab + Carboplatin + Paclitaxel

BNT116 BIOLOGICAL

Intravenous injection

Cohort 10: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (Frail Participants); Cohort 11: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (After Concurrent CRT); Cohort 1A - BNT116 Monotherapy; Cohort 1B - BNT116 Monotherapy; Cohort 2 - BNT116 + Cemiplimab (PD-1/PD-L1 Inhibitor Refractory/Relapsed Participants); Cohort 3 - BNT116 + Docetaxel; Cohort 4 - BNT116 + Cemiplimab (Frail Participants); Cohort 5 - BNT116 + Cemiplimab (After Concurrent Chemoradiotherapy [CRT]); Cohort 6 - BNT116 + Cemiplimab + Carboplatin + Paclitaxel; Cohort 7 - BNT116 + BNT316; Cohort 8: BNT116 + Anti-B7-H3 Antibody Conjugated to Topoisomerase I Inhibitor; Cohort 9: BNT116 + Anti-HER3 Antibody Conjugated to Topoisomerase I Inhibitor; Cohort ALK/RET: BNT116 + ALK TKI or RET TKI; Cohort EGFR : BNT116 + osimertinib

Cemiplimab BIOLOGICAL

Intravenous infusion

Cohort 2 - BNT116 + Cemiplimab (PD-1/PD-L1 Inhibitor Refractory/Relapsed Participants); Cohort 4 - BNT116 + Cemiplimab (Frail Participants); Cohort 5 - BNT116 + Cemiplimab (After Concurrent Chemoradiotherapy [CRT]); Cohort 6 - BNT116 + Cemiplimab + Carboplatin + Paclitaxel

Paclitaxel DRUG

Intravenous infusion

Cohort 6 - BNT116 + Cemiplimab + Carboplatin + Paclitaxel

BNT316 BIOLOGICAL

Intravenous infusion

Cohort 7 - BNT116 + BNT316

anti-B7-H3 antibody conjugated to topoisomerase I inhibitor BIOLOGICAL

Intravenous infusion

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

anti-HER3 antibody conjugated to topoisomerase I inhibitor BIOLOGICAL

Intravenous infusion

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

Bispecific antibody for PD-L1 and VEGF-A BIOLOGICAL

Intravenous infusion

Cohort 10: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (Frail Participants); Cohort 11: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (After Concurrent CRT)

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed NSCLC and measurable disease by RECIST v1.1. Note: Participants in Cohorts 1, 5 and 11 as well as in Cohorts EGFR and ALK/RET do not have to present with measurable disease.
• 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
• Participants in Cohorts 5 and 11 must present with unresectable Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition before receiving pre-study chemoradiotherapy.
• 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 \[PD-1\] / 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 progressive disease either
• 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
• 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 study.
• Cohort 3:

You may not qualify if:

• 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. EXCEPT participants in Cohort EGFR and Cohort ALK/RET.
• 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 days before the first dose of study 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 study treatment starts.
• Other clinically relevant systemic immune suppression within the last 3 months before study enrollment.
• Known history of seropositivity for human immunodeficiency virus (HIV) with cluster of differentiation 4 (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 without additional oxygen).

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (45)

University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536, United States

RECRUITING

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

RECRUITING

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Scientia Clinical Research

Randwick, New South Wales, 2031, Australia

RECRUITING

Royal North Shore Hospital

Sydney, New South Wales, 2065, Australia

RECRUITING

Cancer Research SA

Adelaide, South Australia, 5000, Australia

RECRUITING

Monash Health

Clayton, Victoria, 3168, Australia

RECRUITING

Universitätsklinikum Köln

Cologne, 50937, Germany

RECRUITING

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

Frankfurt, 60488, Germany

RECRUITING

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

RECRUITING

Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR

Mainz, 55131, Germany

RECRUITING

ICON-PRA Budapest, Fázis 1 Vizsgálóhely

Budapest, 1077, Hungary

COMPLETED

Semmelweis Egyetem ÁOK Belgyógyászati és Onkológiai Klinika

Budapest, 1083, Hungary

COMPLETED

National Institute of Oncology

Budapest, 1122, Hungary

RECRUITING

Clinexpert Ltd

Gyöngyös, 3200, Hungary

RECRUITING

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

RECRUITING

Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie

Olsztyn, 10-357, Poland

RECRUITING

NZOZ Medpolonia Sp. Z o.o

Poznan, 60-693, Poland

RECRUITING

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

Warsaw, 02-781, Poland

WITHDRAWN

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

Badalona, 08916, Spain

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

MD Anderson Cancer Center

Madrid, 28033, Spain

RECRUITING

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

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

Madrid, 28050, Spain

RECRUITING

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

Santiago de Compostela, 15706, Spain

RECRUITING

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

RECRUITING

Hospital Universitario y Politecnico La Fe

Valencia, 46026, Spain

RECRUITING

Adana City Training and Research Hospital

Adana, 01370, Turkey (Türkiye)

RECRUITING

Haceteppe Hospital

Ankara, 06100, Turkey (Türkiye)

RECRUITING

Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, 06200, Turkey (Türkiye)

RECRUITING

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

RECRUITING

Koc University Hospital

Istanbul, 34010, Turkey (Türkiye)

RECRUITING

University Medical Faculty Oncology Institute

Istanbul, 34093, Turkey (Türkiye)

RECRUITING

Yeditepe University

Istanbul, 34718, Turkey (Türkiye)

RECRUITING

Ege University School of Medicine Tulay Aktas Oncology Hospital

Izmir, 35100, Turkey (Türkiye)

RECRUITING

Dokuz Eylul Medical School

Izmir, 35330, Turkey (Türkiye)

COMPLETED

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Velindre NHS Trust

Cardiff, CF14 2TL, United Kingdom

RECRUITING

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, L7 8YA, United Kingdom

RECRUITING

Guy's and St Thomas NHS Foundation Trust

London, SE1 9RT, United Kingdom

RECRUITING

University College London Hospitals NHS Foundation Trust

London, W1T 7HA, United Kingdom

RECRUITING

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Multiple Endocrine Neoplasia Type 2a; Diabetes Mellitus, Insulin-Dependent, 12; Parkinson Disease 4, Autosomal Dominant Lewy Body; Lethal Congenital Contracture Syndrome 2

Interventions

cemiplimab; Docetaxel; Carboplatin; Paclitaxel; Antibodies, Bispecific; Vascular Endothelial Growth Factor A; osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vascular Endothelial Growth Factors; Angiogenic Proteins; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Central Study Contacts

BioNTech clinical trials patient information

CONTACT

+49 6131 9084; patients@biontech.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2021
• First Posted: December 2, 2021
• Study Start: June 17, 2022
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): November 1, 2031
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); GB (6); HU (4); TU (9); ES (8); DE (4); PL (4); US (6)