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NCT05142189PHASE1Recruiting

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

BioNTech SE

Start Date

6/17/2022

Completion Date

11/1/2031

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.

Detailed Description

The maximum duration of treatment for each individual participant in this study is: * Cohorts 1 to 4, Cohorts 7 to 10, Cohort EGFR, and Cohort ALK/RET: 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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

BIOLOGICAL

BNT116

BIOLOGICAL

Cemiplimab

DRUG

Docetaxel

DRUG

Carboplatin

DRUG

Paclitaxel

BIOLOGICAL

BNT316

BIOLOGICAL

anti-B7-H3 antibody conjugated to topoisomerase I inhibitor

BIOLOGICAL

anti-HER3 antibody conjugated to topoisomerase I inhibitor

BIOLOGICAL

Bispecific antibody for PD-L1 and VEGF-A

BIOLOGICAL

Osimertinib

BIOLOGICAL

ALK-inhibitor or RET-inhibitor

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Conditions

Non-Small Cell Lung Cancer

Locations

University of Kentucky Chandler Medical Center

Lexington, Kentucky 40536

United States

Norton Cancer Institute

Louisville, Kentucky 40202

United States

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland 21287

United States

Ohio State University

Columbus, Ohio 43210

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

NEXT Virginia

Fairfax, Virginia 22031

United States

Scientia Clinical Research

Randwick, New South Wales 2031

Australia

Royal North Shore Hospital

Sydney, New South Wales 2065

Australia

Cancer Research SA

Adelaide, South Australia 5000

Australia

Monash Health

Clayton, Victoria 3168

Australia

Universitätsklinikum Köln

Cologne, 50937

Germany

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

Frankfurt, 60488

Germany

University Medical Center Hamburg-Eppendorf

Hamburg, 20246

Germany

Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR

Mainz, 55131

Germany

ICON-PRA Budapest, Fázis 1 Vizsgálóhely

Budapest, 1077

Hungary

Semmelweis Egyetem ÁOK Belgyógyászati és Onkológiai Klinika

Budapest, 1083

Hungary

National Institute of Oncology

Budapest, 1122

Hungary

Clinexpert Ltd

Gyöngyös, 3200

Hungary

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214

Poland

Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie

Olsztyn, 10-357

Poland

NZOZ Medpolonia Sp. Z o.o

Poznan, 60-693

Poland

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

Warsaw, 02-781

Poland

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

Badalona, 08916

Spain

Hospital Universitario Vall d'Hebron

Barcelona, 08035

Spain

MD Anderson Cancer Center

Madrid, 28033

Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040

Spain

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

Madrid, 28050

Spain

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

Santiago de Compostela, 15706

Spain

Hospital Universitario Virgen Macarena

Seville, 41009

Spain

Hospital Universitario y Politecnico La Fe

Valencia, 46026

Spain

Adana City Training and Research Hospital

Adana, 01370

Turkey (Türkiye)

Haceteppe Hospital

Ankara, 06100

Turkey (Türkiye)

Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, 06200

Turkey (Türkiye)

Ankara City Hospital

Ankara, 06800

Turkey (Türkiye)

Koc University Hospital

Istanbul, 34010

Turkey (Türkiye)

University Medical Faculty Oncology Institute

Istanbul, 34093

Turkey (Türkiye)

Yeditepe University

Istanbul, 34718

Turkey (Türkiye)

Ege University School of Medicine Tulay Aktas Oncology Hospital

Izmir, 35100

Turkey (Türkiye)

Dokuz Eylul Medical School

Izmir, 35330

Turkey (Türkiye)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ

United Kingdom

Velindre NHS Trust

Cardiff, CF14 2TL

United Kingdom

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, L7 8YA

United Kingdom

Guy's and St Thomas NHS Foundation Trust

London, SE1 9RT

United Kingdom

University College London Hospitals NHS Foundation Trust

London, W1T 7HA

United Kingdom

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE7 7DN

United Kingdom