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

Non-Small Cell Lung Cancer Clinical Trial

— LuCa-MERIT-1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05142189
• Other study ID #: BNT116-01
• Secondary ID: 2021-004739-94
• Status: Recruiting
• Phase: Phase 1
• Start date: June 17, 2022
• Est. completion date: August 2027

Study information

• Verified date: May 2024
• Source: BioNTech SE
• Contact: BioNTech clinical trials patient information
• Phone: +49 6131 9084
• Email: patients[@]biontech.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 cemiplimab or docetaxel in patients with advanced or metastasized non-small cell lung cancer (NSCLC) and unresectable NSCLC after chemoradiotherapy (CRT). Furthermore, the trial aims to establish the safety and feasibility of BNT116 in combination with cemiplimab and chemotherapy (carboplatin+paclitaxel) as neo-adjuvant treatment in resectable NSCLC followed by surgery and adjuvant BNT116 + cemiplimab. The trial will comprise several cohorts for dose confirmation in monotherapy as well as in combinations of BNT116 as mentioned above.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: August 2027
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 in Cohorts 1 to 4 must present with unresectable Stage III or metastatic Stage IV NSCLC by American Joint Commission on Cancer (AJCC) Cancer Staging Manual, Eighth Edition.

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 in Cohorts 2, 3, and 6 must have an Eastern Cooperative Oncology Group performance status (ECOG-PS) =1. Patients in Cohort 1, 4, and 5 with an ECOG-PS of 0-2 are eligible. 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 v4.0 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 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.

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 in Cohorts 1 to 4 if they:

• had radiotherapy or another appropriate therapy for the brain or spinal bone 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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Biological:
• BNT116
intravenous injection
• Cemiplimab
intravenous infusion

Drug:
• Docetaxel
intravenous infusion
• Carboplatin
intravenous infusion
• Paclitaxel
intravenous infusion

Locations

Country	Name	City	State
Germany	Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)	Frankfurt
Germany	University Medical Center Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum Köln	Köln
Germany	Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR	Mainz
Hungary	ICON-PRA Budapest, Fázis 1 Vizsgálóhely	Budapest
Hungary	National Institute of Oncology	Budapest
Hungary	Semmelweis Egyetem ÁOK Belgyógyászati és Onkológiai Klinika	Budapest
Hungary	Clinexpert Ltd	Gyongyos
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie	Olsztyn
Poland	NZOZ Medpolonia Sp. Z o.o	Poznan
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy	Warsaw
Spain	Institut Catala d'Oncologia Badalona, Hospital Germans Trias I Pujol	Badalona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	START Madrid - CIOCC. Grupo Hospital de Madrid (HM) - Centro Integral Oncologico Clara Campal (CIOCC)	Madrid
Spain	Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) - Hospital Clinico Universitario (University Clinical Hospital)	Santiago De Compostela
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitario y Politecnico La Fe	Valencia
Turkey	Ankara City Hospital	Ankara
Turkey	Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital	Ankara
Turkey	Yeditepe University	Istanbul
Turkey	Dokuz Eylul Medical School	Izmir
Turkey	Ege University School of Medicine Tulay Aktas Oncology Hospital	Izmir
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Velindre NHS Trust	Cardiff
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Liverpool
United Kingdom	Guy's and St Thomas NHS Foundation Trust	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	NEXT Virginia	Fairfax	Virginia
United States	Norton Cancer Institute	Louisville	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
BioNTech SE

Countries where clinical trial is conducted

United States,  Germany,  Hungary,  Poland,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohorts 1, 2, 3, 4, and 6: Occurrence of dose-limiting toxicities (DLTs) during Cycle 1		assessed during the first cycle (21 days)
Primary	Cohorts 1 to 6: Occurrence of treatment-emergent adverse events (TEAEs) reported by relationship, seriousness, and grade according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0		up to 27 months
Primary	Cohort 6 only: Occurrence of post-surgical adverse events (AEs) related to BNT116 and cemiplimab		up to 27 months
Primary	Cohort 6 only: Occurrence of treatment-related delays to surgery more than 9 weeks post the last dose of neo-adjuvant treatment		up to 6 months
Secondary	Cohorts 1 to 4: Overall response rate (ORR) defined as the number of patients 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 patients in the efficacy analysis set	up to 27 months
Secondary	Cohorts 1 to 4: Duration of response (DoR) defined as the time from initial response until first objective tumor progression according to RECIST v1.1		up to 27 months
Secondary	Cohorts 1 to 4: Disease control rate (DCR) defined as the number of patients with CR or PR or stable disease (SD) as BOR according to RECIST v1.1 divided by the number of patients in the efficacy analysis set		up to 27 months
Secondary	Cohorts 1 to 4: 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		up to 27 months
Secondary	Cohorts 1 to 4: Progression-free survival (PFS) defined as the time of first trial treatment until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first		up to 48 months
Secondary	All cohorts: Overall survival (OS) defined as the time of first trial treatment until death from any cause		up to 48 months
Secondary	Cohort 5 and 6: Event free survival (EFS) defined as the length of time from first trial treatment to any of the following events: progression of disease, recurrence of disease or death from any cause, whichever occurs first.		up to 48 months
Secondary	Cohort 5 and 6: EFS rate at 12 and 24 months defined as the number of patients without an EFS-defining event divided by the number of patients in the efficacy analysis set.		up to 24 months
Secondary	Cohort 6: Rate of pathologic responses defined as the number of patients with major or complete pathologic response in the surgical specimen from surgery after neo-adjuvant trial treatment divided by the number of patients in the efficacy analysis set.		At time of surgery (approximately after 3 months treatment)
Secondary	Cohort 6: ORR at the end of neo-adjuvant treatment (using RECIST v1.1).		Up to 3 months
Secondary	Cohort 6: Rate of progressive disease at the end of neo-adjuvant treatment (using RECIST v1.1).		Up to 3 months