Non-Small Cell Lung CancerPhase 1LuCa-MERIT-1NCT05142189
Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer
A Phase 1 study testing BNT116, Cemiplimab and Docetaxel in people with Non-Small Cell Lung Cancer, run by BioNTech SE at 45 sites in 8 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- BNT116, Cemiplimab and Docetaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 45 sitesin 8 countries
- Study dates
- 17 Jun 2022to Nov 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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
- 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:
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
45 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
45 sites in 8 countries
Turkey (Türkiye)9 sites, 8 recruiting
- Recruiting
Adana City Training and Research Hospital
Adana, 01370
- Recruiting
Haceteppe Hospital
Ankara, 06100
- Recruiting
Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital
Ankara, 06200
- Recruiting
Ankara City Hospital
Ankara, 06800
- Recruiting
Koc University Hospital
Istanbul, 34010
- Recruiting
University Medical Faculty Oncology Institute
Istanbul, 34093
- Recruiting
Yeditepe University
Istanbul, 34718
- Recruiting
Ege University School of Medicine Tulay Aktas Oncology Hospital
Izmir, 35100
- Completed
Dokuz Eylul Medical School
Izmir, 35330
Spain8 sites, 8 recruiting
- Recruiting
Institut Catala d'Oncologia Badalona, Hospital Germans Trias I Pujol
Badalona, 08916
- Recruiting
Hospital Universitario Vall d'Hebron
Barcelona, 08035
- Recruiting
MD Anderson Cancer Center
Madrid, 28033
- Recruiting
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
- Recruiting
START Madrid - CIOCC. Grupo Hospital de Madrid (HM) - Centro Integral Oncologico Clara Campal (CIOCC)
Madrid, 28050
- Recruiting
Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) - Hospital Clinico Universitario (University Clinical Hospital)
Santiago de Compostela, 15706
- Recruiting
Hospital Universitario Virgen Macarena
Seville, 41009
- Recruiting
Hospital Universitario y Politecnico La Fe
Valencia, 46026
United States6 sites, 6 recruiting
- Recruiting
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
- Recruiting
Ohio State University
Columbus, Ohio, 43210
- Recruiting
NEXT Virginia
Fairfax, Virginia, 22031
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
University of Kentucky Chandler Medical Center
Lexington, Kentucky, 40536
- Recruiting
Norton Cancer Institute
Louisville, Kentucky, 40202
United Kingdom6 sites, 6 recruiting
- Recruiting
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ
- Recruiting
Velindre NHS Trust
Cardiff, CF14 2TL
- Recruiting
The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool, L7 8YA
- Recruiting
Guy's and St Thomas NHS Foundation Trust
London, SE1 9RT
- Recruiting
University College London Hospitals NHS Foundation Trust
London, W1T 7HA
- Recruiting
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, NE7 7DN
Australia4 sites, 4 recruiting
- Recruiting
Cancer Research SA
Adelaide, South Australia, 5000
- Recruiting
Monash Health
Clayton, Victoria, 3168
- Recruiting
Scientia Clinical Research
Randwick, New South Wales, 2031
- Recruiting
Royal North Shore Hospital
Sydney, New South Wales, 2065
Germany4 sites, 4 recruiting
- Recruiting
Universitätsklinikum Köln
Cologne, 50937
- Recruiting
Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)
Frankfurt, 60488
- Recruiting
University Medical Center Hamburg-Eppendorf
Hamburg, 20246
- Recruiting
Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
Mainz, 55131
Hungary4 sites, 2 recruiting
- Completed
ICON-PRA Budapest, Fázis 1 Vizsgálóhely
Budapest, 1077
- Completed
Semmelweis Egyetem ÁOK Belgyógyászati és Onkológiai Klinika
Budapest, 1083
- Recruiting
National Institute of Oncology
Budapest, 1122
- Recruiting
Clinexpert Ltd
Gyöngyös, 3200
Poland4 sites, 3 recruiting
- Recruiting
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-214
- Recruiting
Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie
Olsztyn, 10-357
- Recruiting
NZOZ Medpolonia Sp. Z o.o
Poznan, 60-693
- Withdrawn
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Warsaw, 02-781
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- BNT116, Cemiplimab, Docetaxel, Carboplatin, Paclitaxel
- 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
- Medical subject headings
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BNT116Biological
Intravenous injection
CemiplimabBiological
Intravenous infusion
DocetaxelDrug
Intravenous infusion
CarboplatinDrug
Intravenous infusion
PaclitaxelDrug
Intravenous infusion
BNT316Biological
Intravenous infusion
anti-B7-H3 antibody conjugated to topoisomerase I inhibitorBiological
Intravenous infusion
anti-HER3 antibody conjugated to topoisomerase I inhibitorBiological
Intravenous infusion
Bispecific antibody for PD-L1 and VEGF-ABiological
Intravenous infusion
OsimertinibBiological
Oral
ALK-inhibitor or RET-inhibitorBiological
Oral
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1A - BNT116 Monotherapy | Experimental | Not described Receives: Biological: BNT116 |
| Cohort 1B - BNT116 Monotherapy | Experimental | Not described Receives: Biological: BNT116 |
| Cohort 2 - BNT116 + Cemiplimab (PD-1/PD-L1 Inhibitor Refractory/Relapsed Participants) | Experimental | Not described Receives: Biological: BNT116; Biological: Cemiplimab |
| Cohort 3 - BNT116 + Docetaxel | Experimental | Not described Receives: Biological: BNT116; Drug: Docetaxel |
| Cohort 4 - BNT116 + Cemiplimab (Frail Participants) | Experimental | Not described Receives: Biological: BNT116; Biological: Cemiplimab |
| Cohort 5 - BNT116 + Cemiplimab (After Concurrent Chemoradiotherapy [CRT]) | Experimental | Not described Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: BNT116; Biological: ALK-inhibitor or RET-inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: up to 27 months
Cohort 6 only: Occurrence of Post-Surgical Adverse Events (AEs) Related to BNT116 and Cemiplimab
Measured: 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
Measured: up to 6 months
Secondary outcomes (14)
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Overall Response Rate (ORR)
ORR defined as the number of participants with complete response (CR) or partial response (PR) as best overall response (BOR) according to response evaluation criteria in solid tumors (RECIST) v1.1 divided by the number of participants in the efficacy analysis set.
Measured: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Response (DoR)
DoR defined as the time from initial response until first objective tumor progression according to RECIST v1.1.
Measured: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Disease Control Rate (DCR)
DCR defined as the number of participants with CR or PR or stable disease (SD) as BOR according to RECIST v1.1 divided by the number of participants in the efficacy analysis set.
Measured: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Disease Control
Duration of disease control defined as the time from initial detection of stable disease or response until first objective tumor progression according to RECIST v1.1.
Measured: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Progression-Free Survival (PFS)
PFS defined as the time of first study treatment until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first.
Measured: up to 48 months
Cohorts EGFR (osimertinib): PFS
Defined as the time of first treatment with osimertinib until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first.
Cohort EGFR will enroll only at selected sites in the US.
Measured: up to 48 months
Cohort ALK/RET (ALK TKI or RET TKI): PFS
Defined as the time of first treatment with a ALK TKI or RET TKI until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first.
Cohort ALK/RET will enroll only at selected sites in the US.
Measured: up to 48 months
Cohorts EGFR and ALK/RET: (BNT116): PFS per molecular NSCLC subtype
Defined as the time of first treatment with BNT116 until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first.
Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.
Measured: up to 48 months
Cohorts 1-11: Overall Survival (OS)
OS defined as the time of first study treatment until death from any cause.
Measured: up to 48 months
Cohorts 5, 6 and 11: Event Free Survival (EFS)
EFS defined as the length of time from first study treatment to any of the following events: progression of disease, recurrence of disease or death from any cause, whichever occurs first.
Measured: up to 48 months
Cohort 6: Rate of Pathologic Responses
Rate of pathologic responses defined as the number of participants with major or complete pathologic response in the surgical specimen from surgery after neo-adjuvant study treatment divided by the number of participants in the efficacy analysis set.
Measured: At time of surgery (approximately after 3 months treatment)
Cohorts 5, 6 and 11: EFS Rate at 12 and 24 months
EFS rate defined as the number of participants without an EFS-defining event divided by the number of participants in the efficacy analysis set.
Measured: up to 24 months
Cohort 6: ORR at the End of Neo-Adjuvant Treatment (Using RECIST v1.1)
ORR defined as the number of participants with CR or PR as BOR according to RECIST v1.1 divided by the number of participants in the efficacy analysis set.
Measured: up to 3 months
Cohort 6: Rate of Progressive Disease at the End of Neo-Adjuvant Treatment (Using RECIST v1.1)
Measured: up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2021
- Study start17 Jun 2022
- Primary completionFeb 2030 (estimated)
- Study completionNov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by BioNTech SEThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BioNTech SE
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- BioNTech Responsible Person, Study director, BioNTech SE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05142189
- Sponsor's protocol ID
- BNT116-01
- Other IDs
- 2021-004739-94, 2023-509283-14-00, 2023
- Acronym
- LuCa-MERIT-1
- Status last verified
- Jul 2026
- First submitted
- 24 Nov 2021
- Last updated
- 22 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05142189
- Acronym / sponsor ID
- LuCa-MERIT-1 / BNT116-01
- 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)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- BioNTech SEIndustry (pharma, biotech, devices)
- Study start
- 17 Jun 2022 (actual)
- Primary completion
- Feb 2030 (estimated)
- Study completion
- Nov 2031 (estimated)
- First posted
- 2 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 14
| Arm | Type | Receives |
|---|---|---|
| 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 | Biological: BNT116, Biological: Cemiplimab, Drug: Carboplatin, Drug: PaclitaxelBNT116 + cemiplimab + carboplatin + paclitaxel as neo-adjuvant treatment followed by surgery, thereafter adjuvant treatment with BNT116 + cemiplimab |
| Cohort 7 - BNT116 + BNT316 | Experimental | Biological: BNT116, Biological: BNT316Dose finding for the combination of BNT116 with BNT316 (CTLA4 antibody) with dose escalation of BNT316 |
| Cohort 8: BNT116 + Anti-B7-H3 Antibody Conjugated to Topoisomerase I Inhibitor | Experimental | Biological: BNT116, Biological: anti-B7-H3 antibody conjugated to topoisomerase I inhibitorDose 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 |
| Cohort 9: BNT116 + Anti-HER3 Antibody Conjugated to Topoisomerase I Inhibitor | Experimental | Biological: BNT116, Biological: anti-HER3 antibody conjugated to topoisomerase I inhibitorDose 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 |
| Cohort 10: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (Frail Participants) | Experimental | Biological: BNT116, Biological: Bispecific antibody for PD-L1 and VEGF-ADose 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. |
| Cohort 11: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (After Concurrent CRT) | Experimental | Biological: BNT116, Biological: Bispecific antibody for PD-L1 and VEGF-ADose confirmation for BNT116 in combination with a bispecific antibody for PD-L1 and VEGF-A will be established in participants after concurrent CRT. |
| Cohort EGFR : BNT116 + osimertinib | Experimental | Biological: BNT116, Biological: OsimertinibDose 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. |
| Cohort ALK/RET: BNT116 + ALK TKI or RET TKI | Experimental | Biological: BNT116, Biological: ALK-inhibitor or RET-inhibitorDose 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (43 listed)
- 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.
- EXCEPT
- 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.
- 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).
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BNT116Intravenous injection | Biological | 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 |
| CemiplimabIntravenous infusion | Biological | 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 |
| DocetaxelIntravenous infusion | Drug | Cohort 3 - BNT116 + Docetaxel |
| CarboplatinIntravenous infusion | Drug | Cohort 6 - BNT116 + Cemiplimab + Carboplatin + Paclitaxel |
| PaclitaxelIntravenous infusion | Drug | Cohort 6 - BNT116 + Cemiplimab + Carboplatin + Paclitaxel |
| BNT316Intravenous infusion | Biological | Cohort 7 - BNT116 + BNT316 |
| anti-B7-H3 antibody conjugated to topoisomerase I inhibitorIntravenous infusion | Biological | Cohort 8: BNT116 + Anti-B7-H3 Antibody Conjugated to Topoisomerase I Inhibitor |
| anti-HER3 antibody conjugated to topoisomerase I inhibitorIntravenous infusion | Biological | Cohort 9: BNT116 + Anti-HER3 Antibody Conjugated to Topoisomerase I Inhibitor |
| Bispecific antibody for PD-L1 and VEGF-AIntravenous infusion | Biological | 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) |
| OsimertinibOral | Biological | Cohort EGFR : BNT116 + osimertinib |
| ALK-inhibitor or RET-inhibitorOral | Biological | Cohort ALK/RET: BNT116 + ALK TKI or RET TKI |
Primary outcome
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
Time frame: From first dose of IMP up to 21 days
Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.
Cohorts 1 to 11, EGFR and ALK/RET: Occurrence of Treatment-Emergent Adverse Events (TEAEs) Reported by Relationship, Seriousness, and Grade
Time frame: up to 27 months
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.
Cohort 6 only: Occurrence of Post-Surgical Adverse Events (AEs) Related to BNT116 and Cemiplimab
Time frame: 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
Time frame: up to 6 months
14 secondary outcomes
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Overall Response Rate (ORR)
Time frame: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Response (DoR)
Time frame: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Disease Control Rate (DCR)
Time frame: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Disease Control
Time frame: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Progression-Free Survival (PFS)
Time frame: up to 48 months
Cohorts EGFR (osimertinib): PFS
Time frame: up to 48 months
Cohort ALK/RET (ALK TKI or RET TKI): PFS
Time frame: up to 48 months
Cohorts EGFR and ALK/RET: (BNT116): PFS per molecular NSCLC subtype
Time frame: up to 48 months
Cohorts 1-11: Overall Survival (OS)
Time frame: up to 48 months
Cohorts 5, 6 and 11: Event Free Survival (EFS)
Time frame: up to 48 months
Cohort 6: Rate of Pathologic Responses
Time frame: At time of surgery (approximately after 3 months treatment)
Cohorts 5, 6 and 11: EFS Rate at 12 and 24 months
Time frame: up to 24 months
Cohort 6: ORR at the End of Neo-Adjuvant Treatment (Using RECIST v1.1)
Time frame: up to 3 months
Cohort 6: Rate of Progressive Disease at the End of Neo-Adjuvant Treatment (Using RECIST v1.1)
Time frame: up to 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
BioNTech Responsible Person study director
BioNTech SE
45 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BNT116, Cemiplimab and Docetaxel in people with Non-Small Cell Lung Cancer, run by BioNTech SE at 45 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 43 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in Turkey (Türkiye), Spain, United States, United Kingdom, Australia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact BioNTech clinical trials patient information (+49 6131 9084 ext. 0, patients@biontech.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: From first dose of IMP up to 21 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.