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Clinical Trials in the UK / NCT05142189
Recruiting Phase 1

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 · tracked via the Priya Life Science UK tracker
Sponsor
BioNTech SE
Phase
Phase 1
Started
2022-06-17
Last updated
2026-07-22

Condition(s) studied

Non-Small Cell Lung Cancer

Investigational drug(s) / intervention(s)

BNT116CemiplimabDocetaxelCarboplatinPaclitaxelBNT316anti-B7-H3 antibody conjugated to topoisomerase I inhibitoranti-HER3 antibody conjugated to topoisomerase I inhibitorBispecific antibody for PD-L1 and VEGF-AOsimertinibALK-inhibitor or RET-inhibitor

BNT116: Intravenous injection

Cemiplimab: Intravenous infusion

Docetaxel: Intravenous infusion

Carboplatin: Intravenous infusion

Paclitaxel: Intravenous infusion

BNT316: Intravenous infusion

anti-B7-H3 antibody conjugated to topoisomerase I inhibitor: Intravenous infusion

anti-HER3 antibody conjugated to topoisomerase I inhibitor: Intravenous infusion

Bispecific antibody for PD-L1 and VEGF-A: Intravenous infusion

Osimertinib: Oral

ALK-inhibitor or RET-inhibitor: Oral

Study 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
Key Inclusion Criteria: * 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. 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-study 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 \[PD-1\] / 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-specific inclusion criteria: 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 TPS \>= 50% in tumor cells (as determined locally prior to inclusion in this study). * 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 study. 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 study. 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 study 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 study 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: * Participants' 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 study. Cohort EGFR (will enroll only at selected sites in the US): * Participants' NSCLC must have classical EGFR mutations, i.e., ex19Del or L858R. * Participants must have ongoing treatment with osimertinib. Cohort ALK/RET (will enroll only at selected sites in the US): * Participants' NSCLC must have ALK rearrangement or RET rearrangement. * Participants must have ongoing treatment with a standard of care ALK TKI or RET TKI. Key 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. 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). NOTE: Other protocol defined Inclusion/Exclusion criteria apply to all or some participants depending on the cohort.

Primary outcome measure(s)

Trial sites (45)

FacilityCityRegionStatus
University of Kentucky Chandler Medical Center Lexington Kentucky Recruiting
Norton Cancer Institute Louisville Kentucky Recruiting
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore Maryland Recruiting
Ohio State University Columbus Ohio Recruiting
MD Anderson Cancer Center Houston Texas Recruiting
NEXT Virginia Fairfax Virginia Recruiting
Scientia Clinical Research Randwick New South Wales Recruiting
Royal North Shore Hospital Sydney New South Wales Recruiting
Cancer Research SA Adelaide South Australia Recruiting
Monash Health Clayton Victoria Recruiting
Universitätsklinikum Köln Cologne Germany Recruiting
Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF) Frankfurt Germany Recruiting
University Medical Center Hamburg-Eppendorf Hamburg Germany Recruiting
Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR Mainz Germany Recruiting
ICON-PRA Budapest, Fázis 1 Vizsgálóhely Budapest Hungary Completed
Semmelweis Egyetem ÁOK Belgyógyászati és Onkológiai Klinika Budapest Hungary Completed
National Institute of Oncology Budapest Hungary Recruiting
Clinexpert Ltd Gyöngyös Hungary Recruiting
Uniwersyteckie Centrum Kliniczne Gdansk Poland Recruiting
Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie Olsztyn Poland Recruiting
NZOZ Medpolonia Sp. Z o.o Poznan Poland Recruiting
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Warsaw Poland Withdrawn
Institut Catala d'Oncologia Badalona, Hospital Germans Trias I Pujol Badalona Spain Recruiting
Hospital Universitario Vall d'Hebron Barcelona Spain Recruiting
MD Anderson Cancer Center Madrid Spain Recruiting
Hospital Universitario Fundacion Jimenez Diaz Madrid Spain Recruiting
START Madrid - CIOCC. Grupo Hospital de Madrid (HM) - Centro Integral Oncologico Clara Campal (CIOCC) Madrid Spain Recruiting
Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) - Hospital Clinico Universitario (University Clinical Hospital) Santiago de Compostela Spain Recruiting
Hospital Universitario Virgen Macarena Seville Spain Recruiting
Hospital Universitario y Politecnico La Fe Valencia Spain Recruiting
Adana City Training and Research Hospital Adana Turkey (Türkiye) Recruiting
Haceteppe Hospital Ankara Turkey (Türkiye) Recruiting
Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital Ankara Turkey (Türkiye) Recruiting
Ankara City Hospital Ankara Turkey (Türkiye) Recruiting
Koc University Hospital Istanbul Turkey (Türkiye) Recruiting
University Medical Faculty Oncology Institute Istanbul Turkey (Türkiye) Recruiting
Yeditepe University Istanbul Turkey (Türkiye) Recruiting
Ege University School of Medicine Tulay Aktas Oncology Hospital Izmir Turkey (Türkiye) Recruiting
Dokuz Eylul Medical School Izmir Turkey (Türkiye) Completed
Cambridge University Hospitals NHS Foundation Trust Cambridge United Kingdom Recruiting

+ 5 more sites — see the full list on the official registry below.

On this site

📄 Libtayo (cemiplimab) drug profile → 📄 Tagrisso (osimertinib) drug profile →

More BioNTech SE trials in the UK

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05142189 on ClinicalTrials.gov ↗ ← All trials in the UK