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NCT05142189 | RECRUITING | Non-Small Cell Lung Cancer

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

BioNTech SE

Brief Summary:

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, or an anti-human epidermal growth factor receptor 3 (HER3) antibody conjugated to a topoisomerase I inhibitor in patients 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 patients with NSCLC in advanced or metastatic stage in Cohorts 1 to 4 and Cohorts 7 to 9, unresectable NSCLC Stage III in Cohort 5, and resectable NSCLC of Stage II and III in Cohort 6.

Condition or disease

Non-Small Cell Lung Cancer

Intervention/treatment

BNT116

Cemiplimab

Docetaxel

Carboplatin

Paclitaxel

BNT316

anti-B7-H3 antibody conjugated to topoisomerase I inhibitor

anti-HER3 antibody conjugated to topoisomerase I inhibitor

Phase

PHASE1

Detailed Description:

The maximum duration of treatment for each individual patient in this trial is: * Cohorts 1 to 4, and Cohorts 7 to 9: 24 months * Cohort 5: 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

Study Type : INTERVENTIONAL
Estimated Enrollment : 220 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : LuCa-MERIT-1: First-in-human, Open Label, Phase I Dose Confirmation Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer
Actual Study Start Date : 2022-06-17
Estimated Primary Completion Date : 2030-02
Estimated Study Completion Date : 2031-11

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
Key Inclusion Criteria
  • * Patients must have histologically confirmed NSCLC and measurable disease by RECIST v1.1. Note: Patients in Cohort 1 and Cohort 5 do not have to present with measurable disease.
  • 1. Patients 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. Patients in Cohort 5 must present with unresectable Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition before receiving pre-trial chemoradiotherapy.
  • 3. Patients in Cohort 6 with the initial diagnosis of resectable Stage II and Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition.
  • * Patients in Cohorts 2, 4, 5, and 6 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).
  • * Patients must have an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤1, except for patients in Cohorts 1, 4, and 5 who are eligible with an ECOG-PS of 0-2.
  • Cohort-specific inclusion criteria
    • Cohort 1
      • * Patients' 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 patient is not candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor and/or another line of systemic therapy). Note: Patients newly enrolled in Cohort 1B under clinical trial protocol v5.0 and subsequent versions of the clinical trial protocol must consent to mandatory blood sampling for peripheral blood mononuclear cells (PBMCs).
      • * Patients who are to start cemiplimab at Cycle 3 must present with PD-L1 expression of tumor proportion score (TPS) ≥1% in tumor cells (as determined locally).
      • Cohort 2
        • * Patients must present with PD-L1 expression of tumor proportion score (TPS) ≥50% in tumor cells (as determined locally prior to inclusion in this trial).
        • * Patients 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
          • * Patients' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a patient is not candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor).
          • * Patients must present with progressive disease.
          • Cohort 4
            • * Patients' 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
              • * Patients' NSCLC must have been considered unresectable due to patients' condition and/or tumor-related factors and the patients must have undergone chemoradiotherapy before entering the trial.
              • Cohort 6
                • * Patients' NSCLC must be considered technically and medically resectable.
                • * Patients must be considered eligible for neo-adjuvant treatment.
                • Cohort 7
                  • * Patients' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a patient is not a candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor). Note 1: Patients 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), vascular endothelial growth factor (VEGF) or VEGF receptor (VEGFR) inhibitor as monotherapy or part of a combination therapy. Note 2: If the patient's prior therapies included a CTLA-4 inhibitor, the patient must be able to tolerate (additional) treatment with the CTLA-4 inhibitor.
                  • * Patients must present with progressive disease at trial enrollment.
                  • * Patients must consent to mandatory blood sampling for PBMCs.
                  • Cohorts 8 \& 9
                    • * Patients' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a patient is not a candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor).
                    • * Patients must present with progressive disease at trial enrollment.
                    • Key Exclusion Criteria
                      • * Ongoing active systemic treatment against NSCLC.
                      • * Presence of a driver mutation for which approved target therapies are available except if the patient 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: Patients 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. Patients with leptomeningeal disease are excluded. Patients with known brain or spinal metastases may be eligible for all Cohorts, except for Cohort 5 and 6, 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 (i.e., 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); patients 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 patients in Cohort 5 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 \<350 cells/µL 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).
                      • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply to all or some patients depending on the cohort.
Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer

Location Details

NCT05142189

Please Choose a site

How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, Kentucky

University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States, 40536

RECRUITING

United States, Kentucky

Norton Cancer Institute

Louisville, Kentucky, United States, 40202

RECRUITING

United States, Maryland

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States, 21287

RECRUITING

United States, Virginia

NEXT Virginia

Fairfax, Virginia, United States, 22031

RECRUITING

Germany,

Hospital Nordwest GmbH - Institute for Clinical -Onkological Research (IKF)

Frankfurt, Germany, 60488

RECRUITING

Germany,

University Medical Center Hamburg-Eppendorf

Hamburg, Germany, 20246

RECRUITING

Germany,

University Hospital Cologne

Köln, Germany, 50937

RECRUITING

Germany,

University Medicine of Johannes Gutenberg University Mainz Koer

Mainz, Germany, 55131

RECRUITING

Hungary,

ICON-PRA Budapest, Phase 1 testing site

Budapest, Hungary, 1077

RECRUITING

Hungary,

Semmelweis University Department of Internal Medicine and Oncology

Budapest, Hungary, 1083

RECRUITING

Hungary,

National Institute of Oncology

Budapest, Hungary, 1122

RECRUITING

Hungary,

Clinexpert Ltd

Gyongyos, Hungary, 3200

RECRUITING

Poland,

University Clinical Center

Gdańsk, Poland, 80-214

RECRUITING

Poland,

The Warmin Mazurski Center for Disease Pluc in Olstna

Olsztyn, Poland, 10-357

RECRUITING

Poland,

NZOZ Medpolonia Sp. Z o.o

Poznań, Poland, 60-693

RECRUITING

Poland,

National Oncology Institute Maria Sklodowska-Curie Panniego Research Institute

Warsaw, Poland, 02-781

RECRUITING

Spain,

Institute Catalan of Badalona Oncology, Hospital Brothers Trias I Hill

Badalona, Spain, 08916

RECRUITING

Spain,

Vall d'Hebron University Hospital

Barcelona, Spain, 08035

RECRUITING

Spain,

MD Anderson Cancer Center

Madrid, Spain, 28033

RECRUITING

Spain,

Jimenez Diaz Foundation University Hospital

Madrid, Spain, 28040

RECRUITING

Spain,

START MADRID - CIOCC. Grupo Hospital de Madrid (HM) - Clear Clear Campal Integral Center (CIOCC)

Madrid, Spain, 28050

RECRUITING

Spain,

University Hospital Complex of Santiago de Compostela (Chus) - University Clinic Hospital (University Clinical Hospital)

Santiago de Compostela, Spain, 15706

RECRUITING

Spain,

Virgen Macarena University Hospital

Sevilla, Spain, 41009

RECRUITING

Spain,

UNIVERSITY AND POLITECNIC HOSPITAL LA FE

Valencia, Spain, 46026

NOT YET RECRUITING

Turkey,

ADANA ELER HOSPITAL

Adana, Turkey, 01230

RECRUITING

Turkey,

Doteppe Hospital

Ankara, Turkey, 06100

RECRUITING

Turkey,

Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, Turkey, 06200

RECRUITING

Turkey,

Ankara City Hospital

Ankara, Turkey, 06800

RECRUITING

Turkey,

Koc University Hospital

Istanbul, Turkey, 34010

NOT YET RECRUITING

Turkey,

University Medical Faculty Oncology Institute

Istanbul, Turkey, 34093

RECRUITING

Turkey,

Yeditepe University

Istanbul, Turkey, 34718

RECRUITING

Turkey,

Ege University School of Medicine Tulay Aktas Oncology Hospital

Izmir, Turkey, 35100

RECRUITING

Turkey,

Nine September Medical School

İzmir, Turkey, 35330

RECRUITING

United Kingdom,

Cambridge University Hospitals NHS Foundation Trust

Cambridge, United Kingdom, CB2 0QQ

NOT YET RECRUITING

United Kingdom,

Velindre NHS Trust

Cardiff, United Kingdom, CF14 2TL

RECRUITING

United Kingdom,

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, United Kingdom, Tail

RECRUITING

United Kingdom,

Guy's and St Thomas NHS Foundation Trust

London, United Kingdom, SE1 9RT

RECRUITING

United Kingdom,

University College London Hospitals NHS Foundation Trust

London, United Kingdom, W1t 7ha

RECRUITING

United Kingdom,

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle Upon Tyne, United Kingdom, Nan bosom