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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05142189




Registration number
NCT05142189
Ethics application status
Date submitted
24/11/2021
Date registered
2/12/2021
Date last updated
9/07/2025

Titles & IDs
Public title
Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer
Scientific 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
Secondary ID [1] 0 0
2021-004739-94
Secondary ID [2] 0 0
BNT116-01
Universal Trial Number (UTN)
Trial acronym
LuCa-MERIT-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - BNT116
Treatment: Other - Cemiplimab
Treatment: Drugs - Docetaxel
Treatment: Drugs - Carboplatin
Treatment: Drugs - Paclitaxel
Treatment: Other - BNT316
Treatment: Other - anti-B7-H3 antibody conjugated to topoisomerase I inhibitor
Treatment: Other - anti-HER3 antibody conjugated to topoisomerase I inhibitor

Experimental: Cohort 1A - BNT116 monotherapy -

Experimental: Cohort 1B - BNT116 monotherapy -

Experimental: Cohort 2 - BNT116 + cemiplimab (PD-1/PD-L1 inhibitor refractory/relapsed patients) -

Experimental: Cohort 3 - BNT116 + docetaxel -

Experimental: Cohort 4 - BNT116 + cemiplimab (frail patients) -

Experimental: Cohort 5 - BNT116 + cemiplimab (after concurrent chemoradiotherapy [CRT]) -

Experimental: Cohort 6 - BNT116 + cemiplimab + carboplatin + paclitaxel - BNT116 + cemiplimab + carboplatin + paclitaxel as neo-adjuvant treatment followed by surgery, thereafter adjuvant treatment with BNT116 + cemiplimab

Experimental: Cohort 7 - BNT116 + BNT316 - Dose finding for the combination of BNT116 with BNT316 (CTLA4 antibody) with dose escalation of BNT316

Experimental: Cohort 8: BNT116 + anti-B7-H3 antibody conjugated to topoisomerase I inhibitor - 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

Experimental: Cohort 9: BNT116 + anti-HER3 antibody conjugated to topoisomerase I inhibitor - Dose finding 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


Treatment: Other: BNT116
intravenous injection

Treatment: Other: Cemiplimab
intravenous infusion

Treatment: Drugs: Docetaxel
intravenous infusion

Treatment: Drugs: Carboplatin
intravenous infusion

Treatment: Drugs: Paclitaxel
intravenous infusion

Treatment: Other: BNT316
intravenous infusion

Treatment: Other: anti-B7-H3 antibody conjugated to topoisomerase I inhibitor
intravenous infusion

Treatment: Other: anti-HER3 antibody conjugated to topoisomerase I inhibitor
intravenous infusion
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohorts 1, 2, 3, 4, 6, 7, 8, and 9: Occurrence of dose-limiting toxicities (DLTs) during the DLT observation period
Timepoint [1] 0 0
From first dose of IMP up to 21 days
Primary outcome [2] 0 0
Cohorts 1 to 9: Occurrence of treatment-emergent adverse events (TEAEs) reported by relationship, seriousness, and grade
Timepoint [2] 0 0
up to 27 months
Primary outcome [3] 0 0
Cohort 6 only: Occurrence of post-surgical adverse events (AEs) related to BNT116 and cemiplimab
Timepoint [3] 0 0
up to 27 months
Primary outcome [4] 0 0
Cohort 6 only: Occurrence of treatment-related delays to surgery more than 9 weeks post the last dose of neo-adjuvant treatment
Timepoint [4] 0 0
up to 6 months
Secondary outcome [1] 0 0
Cohorts 1, 2, 3, 4, 7, 8, and 9: Overall response rate (ORR)
Timepoint [1] 0 0
up to 27 months
Secondary outcome [2] 0 0
Cohorts 1, 2, 3, 4, 7, 8, and 9: Duration of response (DoR)
Timepoint [2] 0 0
up to 27 months
Secondary outcome [3] 0 0
Cohorts 1, 2, 3, 4, 7, 8, and 9: Disease control rate (DCR)
Timepoint [3] 0 0
up to 27 months
Secondary outcome [4] 0 0
Cohorts 1, 2, 3, 4, 7, 8, and 9: 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
Timepoint [4] 0 0
up to 27 months
Secondary outcome [5] 0 0
Cohorts 1, 2, 3, 4, 7, 8, and 9: Progression-free survival (PFS)
Timepoint [5] 0 0
up to 48 months
Secondary outcome [6] 0 0
All cohorts: Overall survival (OS)
Timepoint [6] 0 0
up to 48 months
Secondary outcome [7] 0 0
Cohort 5 and 6: Event free survival (EFS)
Timepoint [7] 0 0
up to 48 months
Secondary outcome [8] 0 0
Cohort 5 and 6: EFS rate at 12 and 24 months
Timepoint [8] 0 0
up to 24 months
Secondary outcome [9] 0 0
Cohort 6: Rate of pathologic responses
Timepoint [9] 0 0
At time of surgery (approximately after 3 months treatment)
Secondary outcome [10] 0 0
Cohort 6: ORR at the end of neo-adjuvant treatment (using RECIST v1.1)
Timepoint [10] 0 0
Up to 3 months
Secondary outcome [11] 0 0
Cohort 6: Rate of progressive disease at the end of neo-adjuvant treatment (using RECIST v1.1)
Timepoint [11] 0 0
Up to 3 months

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2031
Actual
Sample size
Target
220
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Scientia Clinical Research - Randwick
Recruitment hospital [2] 0 0
Cancer Research SA - Adelaide
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Kentucky
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Virginia
Country [4] 0 0
Germany
State/province [4] 0 0
Frankfurt
Country [5] 0 0
Germany
State/province [5] 0 0
Hamburg
Country [6] 0 0
Germany
State/province [6] 0 0
Köln
Country [7] 0 0
Germany
State/province [7] 0 0
Mainz
Country [8] 0 0
Hungary
State/province [8] 0 0
Budapest
Country [9] 0 0
Hungary
State/province [9] 0 0
Gyongyos
Country [10] 0 0
Poland
State/province [10] 0 0
Gdansk
Country [11] 0 0
Poland
State/province [11] 0 0
Olsztyn
Country [12] 0 0
Poland
State/province [12] 0 0
Poznan
Country [13] 0 0
Poland
State/province [13] 0 0
Warsaw
Country [14] 0 0
Spain
State/province [14] 0 0
Badalona
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Madrid
Country [17] 0 0
Spain
State/province [17] 0 0
Santiago De Compostela
Country [18] 0 0
Spain
State/province [18] 0 0
Sevilla
Country [19] 0 0
Spain
State/province [19] 0 0
Valencia
Country [20] 0 0
Turkey
State/province [20] 0 0
Adana
Country [21] 0 0
Turkey
State/province [21] 0 0
Ankara
Country [22] 0 0
Turkey
State/province [22] 0 0
Istanbul
Country [23] 0 0
Turkey
State/province [23] 0 0
Izmir
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Cambridge
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Cardiff
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Liverpool
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BioNTech SE
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
BioNTech Responsible Person
Address 0 0
BioNTech SE
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BioNTech clinical trials patient information
Address 0 0
Country 0 0
Phone 0 0
+49 6131 9084
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05142189