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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 · BioNTech SE
In plain English
Click the button to translate this study into plain language — what it is, who qualifies, and what participation looks like.
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
About this study
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
Key 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-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 \[PD-1\] / 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-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 tumor proportion score (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 \[SpO2\] without additional oxygen).
NOTE: Other protocol defined Inclusion/Exclusion criteria apply to all or some participants depending on the cohort.
Study design
Enrollment target: 320 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2022-06-17
Estimated completion: 2031-11
Last updated: 2026-04-14
Interventions
Biological: BNT116Biological: CemiplimabDrug: DocetaxelDrug: CarboplatinDrug: PaclitaxelBiological: BNT316Biological: anti-B7-H3 antibody conjugated to topoisomerase I inhibitorBiological: anti-HER3 antibody conjugated to topoisomerase I inhibitorBiological: Bispecific antibody for PD-L1 and VEGF-ABiological: OsimertinibBiological: ALK-inhibitor or RET-inhibitor
Primary outcomes
- • 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 (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 (up to 27 months)
- • Cohort 6 only: Occurrence of Post-Surgical Adverse Events (AEs) Related to BNT116 and Cemiplimab (up to 27 months)
Sponsor
BioNTech SE · industry
Contacts & investigators
ContactBioNTech clinical trials patient information · contact · patients@biontech.de · +49 6131 9084
InvestigatorBioNTech Responsible Person · study_director, BioNTech SE
All locations (44)
University of Kentucky Chandler Medical CenterRecruiting
Lexington, Kentucky, United States
Norton Cancer InstituteRecruiting
Louisville, Kentucky, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer CenterRecruiting
Baltimore, Maryland, United States
MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
NEXT VirginiaRecruiting
Fairfax, Virginia, United States
Scientia Clinical ResearchRecruiting
Randwick, New South Wales, Australia
Royal North Shore HospitalRecruiting
Sydney, New South Wales, Australia
Cancer Research SARecruiting
Adelaide, South Australia, Australia
Monash HealthRecruiting
Clayton, Victoria, Australia
Universitätsklinikum KölnRecruiting
Cologne, Germany
Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)Recruiting
Frankfurt, Germany
University Medical Center Hamburg-EppendorfRecruiting
Hamburg, Germany
Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeRRecruiting
Mainz, Germany
ICON-PRA Budapest, Fázis 1 VizsgálóhelyCompleted
Budapest, Hungary
Semmelweis Egyetem ÁOK Belgyógyászati és Onkológiai KlinikaRecruiting
Budapest, Hungary
National Institute of OncologyRecruiting
Budapest, Hungary
Clinexpert LtdRecruiting
Gyöngyös, Hungary
Uniwersyteckie Centrum KliniczneRecruiting
Gdansk, Poland
Warminsko Mazurskie Centrum Chorob Pluc w OlsztynieRecruiting
Olsztyn, Poland
NZOZ Medpolonia Sp. Z o.oRecruiting
Poznan, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut BadawczyWithdrawn
Warsaw, Poland
Institut Catala d'Oncologia Badalona, Hospital Germans Trias I PujolRecruiting
Badalona, Spain
Hospital Universitario Vall d'HebronRecruiting
Barcelona, Spain
MD Anderson Cancer CenterRecruiting
Madrid, Spain
Hospital Universitario Fundacion Jimenez DiazRecruiting
Madrid, Spain
START Madrid - CIOCC. Grupo Hospital de Madrid (HM) - Centro Integral Oncologico Clara Campal (CIOCC)Recruiting
Madrid, Spain
Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) - Hospital Clinico Universitario (University Clinical Hospital)Recruiting
Santiago de Compostela, Spain
Hospital Universitario Virgen MacarenaRecruiting
Seville, Spain
Hospital Universitario y Politecnico La FeRecruiting
Valencia, Spain
Adana City Training and Research HospitalRecruiting
Adana, Turkey (Türkiye)
Haceteppe HospitalRecruiting
Ankara, Turkey (Türkiye)
Dr. Abdurrahman Yurtaslan Oncology Training and Research HospitalRecruiting
Ankara, Turkey (Türkiye)
Ankara City HospitalRecruiting
Ankara, Turkey (Türkiye)
Koc University HospitalRecruiting
Istanbul, Turkey (Türkiye)
University Medical Faculty Oncology InstituteRecruiting
Istanbul, Turkey (Türkiye)
Yeditepe UniversityRecruiting
Istanbul, Turkey (Türkiye)
Ege University School of Medicine Tulay Aktas Oncology HospitalRecruiting
Izmir, Turkey (Türkiye)
Dokuz Eylul Medical SchoolCompleted
Izmir, Turkey (Türkiye)
Cambridge University Hospitals NHS Foundation TrustRecruiting
Cambridge, United Kingdom
Velindre NHS TrustRecruiting
Cardiff, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation TrustRecruiting
Liverpool, United Kingdom
Guy's and St Thomas NHS Foundation TrustRecruiting
London, United Kingdom
University College London Hospitals NHS Foundation TrustRecruiting
London, United Kingdom
The Newcastle Upon Tyne Hospitals NHS Foundation TrustRecruiting
Newcastle upon Tyne, United Kingdom