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JOURNAL ONKOLOGIE – STUDIE
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

Rekrutierend

NCT-Nummer:
NCT05142189

Studienbeginn:
Juni 2022

Letztes Update:
16.04.2024

Wirkstoff:
BNT116, Cemiplimab, Docetaxel, Carboplatin, Paclitaxel

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
BioNTech SE

Collaborator:
-

Studienleiter

BioNTech Responsible Person
Study Director
BioNTech SE

Kontakt

BioNTech clinical trials patient information
Kontakt:
Phone: +49 6131 9084
E-Mail: patients@biontech.de» Kontaktdaten anzeigen

Studienlocations
(3 von 34)

Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)
60488 Frankfurt
(Hessen)
GermanyRekrutierend» Google-Maps
University Medical Center Hamburg-Eppendorf
20246 Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps
Universitätsklinikum Köln
50937 Köln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
55131 Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Norton Cancer Institute
40202 Louisville
United StatesRekrutierend» Google-Maps
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
21287 Baltimore
United StatesRekrutierend» Google-Maps
ICON-PRA Budapest, Fázis 1 Vizsgálóhely
1077 Budapest
HungaryRekrutierend» Google-Maps
Semmelweis Egyetem ÁOK Belgyógyászati és Onkológiai Klinika
1083 Budapest
HungaryRekrutierend» Google-Maps
National Institute of Oncology
1122 Budapest
HungaryRekrutierend» Google-Maps
Uniwersyteckie Centrum Kliniczne
80-214 Gdańsk
PolandRekrutierend» Google-Maps
Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie
10-357 Olsztyn
PolandRekrutierend» Google-Maps
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
02-781 Warsaw
PolandRekrutierend» Google-Maps
Institut Catala d'Oncologia Badalona, Hospital Germans Trias I Pujol
08916 Badalona
SpainRekrutierend» Google-Maps
Hospital Universitario Vall d'Hebron
08035 Barcelona
SpainRekrutierend» Google-Maps
Hospital Universitario Fundacion Jimenez Diaz
28040 Madrid
SpainRekrutierend» Google-Maps
START Madrid - CIOCC. Grupo Hospital de Madrid (HM) - Centro Integral Oncologico Clara Campal (CIOCC)
28050 Madrid
SpainRekrutierend» Google-Maps
Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) - Hospital Clinico Universitario (University Clinical Hospital)
15706 Santiago De Compostela
SpainRekrutierend» Google-Maps
Hospital Universitario Virgen Macarena
41009 Sevilla
SpainRekrutierend» Google-Maps
Hospital Universitario y Politecnico La Fe
46026 Valencia
SpainRekrutierend» Google-Maps
Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital
06200 Ankara
TurkeyRekrutierend» Google-Maps
Ege University School of Medicine Tulay Aktas Oncology Hospital
35100 Izmir
TurkeyRekrutierend» Google-Maps
Cambridge University Hospitals NHS Foundation Trust
CB2 0QQ Cambridge
United KingdomNoch nicht rekrutierend» Google-Maps
Velindre NHS Trust
CF14 2TL Cardiff
United KingdomNoch nicht rekrutierend» Google-Maps
The Clatterbridge Cancer Centre NHS Foundation Trust
L7 8YA Liverpool
United KingdomNoch nicht rekrutierend» Google-Maps
Guy's and St Thomas NHS Foundation Trust
SE1 9RT London
United KingdomNoch nicht rekrutierend» Google-Maps
University College London Hospitals NHS Foundation Trust
W1T 7HA London
United KingdomRekrutierend» Google-Maps
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
NE7 7DN Newcastle Upon Tyne
United KingdomNoch nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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 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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. Cohorts 1, 2, 3, 4, and 6: Occurrence of dose-limiting toxicities (DLTs) during Cycle 1 (Time Frame - assessed during the first cycle (21 days))

2. 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 (Time Frame - up to 27 months)

3. Cohort 6 only: Occurrence of post-surgical adverse events (AEs) related to BNT116 and cemiplimab (Time Frame - up to 27 months)

4. 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)

Secondary outcome:

1. 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) (Time Frame - 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

2. 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 (Time Frame - up to 27 months)

3. 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 (Time Frame - up to 27 months)

4. 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 (Time Frame - up to 27 months)

5. 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 (Time Frame - up to 48 months)

6. All cohorts: Overall survival (OS) defined as the time of first trial treatment until death from any cause (Time Frame - up to 48 months)

7. 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. (Time Frame - up to 48 months)

8. 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. (Time Frame - up to 24 months)

9. 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. (Time Frame - At time of surgery (approximately after 3 months treatment))

10. Cohort 6: ORR at the end of neo-adjuvant treatment (using RECIST v1.1). (Time Frame - Up to 3 months)

11. Cohort 6: Rate of progressive disease at the end of neo-adjuvant treatment (using RECIST v1.1). (Time Frame - Up to 3 months)

Studien-Arme

  • 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

Geprüfte Regime

  • BNT116:
    intravenous injection
  • Cemiplimab:
    intravenous infusion
  • Docetaxel:
    intravenous infusion
  • Carboplatin:
    intravenous infusion
  • Paclitaxel:
    intravenous infusion

Quelle: ClinicalTrials.gov


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