LuCa-MERIT-1: 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 (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05142189

Collaborator

(none)

Enrollment

Locations

Arms

60.5

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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 cemiplimab or in combination with docetaxel in patients with advanced or metastasized non-small cell lung cancer (NSCLC). The trial will comprise several cohorts for dose confirmation in monotherapy as well as in combinations.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Biological: BNT116 Biological: Cemiplimab Drug: Docetaxel	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

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 :

Jun 17, 2022

Anticipated Primary Completion Date :

May 1, 2025

Anticipated Study Completion Date :

Jul 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 - BNT116 monotherapy	Biological: BNT116 intravenous injection
Experimental: Cohort 2 - BNT116 + cemiplimab	Biological: BNT116 intravenous injection Biological: Cemiplimab intravenous infusion
Experimental: Cohort 3 - BNT116 + docetaxel	Biological: BNT116 intravenous injection Drug: Docetaxel intravenous infusion
Experimental: Cohort 4 - BNT116 + cemiplimab	Biological: BNT116 intravenous injection Biological: Cemiplimab intravenous infusion

Outcome Measures

Primary Outcome Measures

Occurrence of dose-limiting toxicities (DLTs) during Cycle 1 [assessed during the first cycle (21 days)]
Occurrence of unsolicited 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]

Secondary Outcome Measures

Overall response rate (ORR) defined as the number of patients with complete response (CR) or partial response (PR) as best overall response (BOR) [up to 27 months]
according to response evaluation criteria in solid tumors (RECIST) v1.1 divided by the number of patients in the efficacy analysis set
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]
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]
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]
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]
Overall survival (OS) defined as the time of first trial treatment until death from any cause [up to 48 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Patients must have histologically confirmed unresectable Stage III or metastatic Stage IV NSCLC and measurable disease by RECIST v1.1. Note: Patients in Cohort 1 do not have to have measurable disease.
Patients in Cohorts 2 and 4 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) and must have recovered to stage 1 or 0 from any previous PD-1/PD-L1-related toxicity or be on a stable hormone substitute therapy.
Patients in Cohorts 2 and 3 must have an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤1. Patients in Cohort 1 and 4 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).

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

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 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).

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.

Key Exclusion Criteria:

Ongoing active systemic treatment against NSCLC.
Presence of a driver mutation for which approved target therapies are available.
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 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.
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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	ICON-PRA Budapest, Fázis 1 Vizsgálóhely	Budapest	Hungary	1077
2	Semmelweis Egyetem ÁOK Belgyógyászati és Onkológiai Klinika	Budapest	Hungary	1083
3	National Institute of Oncology	Budapest	Hungary	1122
4	Clinexpert Ltd	Gyongyos	Hungary	3200