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JOURNAL ONKOLOGIE – STUDIE

Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT411

Rekrutierend

NCT-Nummer:
NCT04101357

Studienbeginn:
Juni 2020

Letztes Update:
12.03.2021

Wirkstoff:
BNT411, Atezolizumab, Carboplatin, Etoposide

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

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
BioNTech SE

Collaborator:
-

Studienleiter

BioNTech Responsible Person
Study Director
BioNTech SE

Kontakt

BioNTech clinical trials patient information
Kontakt:
Phone: +49 6131 9084
Phone (ext.): 1919
E-Mail: patients@biontech.de
» Kontaktdaten anzeigen

Studienlocations
(3 von 8)

Universitaetsklinikum Koeln
50937 Koeln
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Universitaetsmedizin der Johannes Gutenberg Universitat Mainz KoeR - (Recruiting only for part 1B and part 2)
55131 Mainz
(Rheinland-Pfalz)
GermanyNoch nicht rekrutierend» Google-Maps
Cedars-Sinai Medical Center
90048 Los Angeles
United StatesRekrutierend» Google-Maps
Northwestern Medical Faculty Foundation
60611 Chicago
United StatesRekrutierend» Google-Maps
Hospital Universitari Vall d'Hebron
08035 Barcelona
SpainRekrutierend» Google-Maps
START Madrid - CIOCC. Grupo Hospital de Madrid (HM) - Centro Integral Oncologico Clara Campal (CIOCC)
28050 Madrid
SpainRekrutierend» Google-Maps
Edinburgh Cancer Research Centre
EH4 2XU Edinburgh
United KingdomRekrutierend» Google-Maps
Sarah Cannon Research Institute
W1G 6AD London
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This first-in-human (FIH) trial aims to establish a safe dose of BNT411 as a monotherapy and

in combination with atezolizumab, carboplatin and etoposide. BNT411 is a toll-like receptor 7

(TLR7) agonist which is expected to mount broad innate and adaptive immune reactions,

especially in combination with cytotoxic therapies and immune checkpoint inhibitors.

Ein-/Ausschlusskriterien

Inclusion Criteria:

For Part 1A:

- Histologically confirmed solid tumor (cytology is allowed for NSCLC, SCLC and

pancreatic cancer) that is metastatic or unresectable and for which there is no

available standard therapy likely to confer clinical benefit, or patients who are not

candidates for such available therapy.

For Part 1B:

- Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration

Lung Study Group [VALG] staging system) who received no prior chemotherapy for

extensive stage disease.

- Those treated with prior chemo/radiotherapy with curative intent for LS-SCLC should be

treatment-free for at least 6 months since last chemo/radiotherapy.

- Has no interstitial lung disease or active, non-infectious pneumonitis.

For Both Part 1A and Part 1B

- Male and female ≥ 18 years of age.

- Must sign an informed consent form (ICF) indicating that he or she understands the

purpose of and procedures required for the trial and are willing to participate in the

trial prior to any trial related assessments or procedures.

- ECOG performance status of 0 to 1.

- Measurable disease according to RECIST 1.1.

- Albumin level at screening ≥30 g/L.

- Able to receive the first administration of trial treatment within 42 days from the

last documented disease progression.

- Adequate coagulation function at Screening as determined by:

1. International normalized ratio (INR) or prothrombin time ≤1.5 x upper limit

normal (ULN; unless on therapeutic anticoagulants with values within therapeutic

window),

2. Activated partial thromboplastin time (aPTT) ≤1.5 x ULN (unless on therapeutic

anticoagulants with values within therapeutic window).

- Adequate hematologic function at Screening as determined by:

1. White blood count (WBC) ≥3 x 10^9/L

2. Absolute neutrophil count (ANC) ≥1.5 x 10^9/L (patient may not use

granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony

stimulating factor (GM-CSF) to achieve these WBC and ANC levels),

3. Platelet count ≥100 x 10^9/L,

4. Hemoglobin (Hgb) ≥9.0 g/dL (may not transfuse or use erythropoietin to obtain

this Hgb level).

- Adequate hepatic function at Screening as determined by:

1. Total bilirubin ≤ 1.5 mg/dL (or ≤ 2.0 mg/dL for patients with known Gilbert's

syndrome),

2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN;

or ≤5 x ULN in patients with metastatic liver disease.

- Adequate renal function at Screening as determined by:

a. Glomerular filtration rate (GFR) ≥60 mL/min/1.73 m²- e.g., according to the

abbreviated Modification of Diet in Renal Disease (MDRD) equation: GFR = 186 ×

(SCr-1.154) × (age-0.203) (where SCr, the serum creatinine level, is expressed in

mg/dL; multiplied by 0.742 if the patient is female; multiplied by 1.212, if the

patient is African-American (Levey et al., 1999).

- Able to attend trial visits as required by the protocol.

- Women of childbearing potential (WOCBP) must have a negative serum (beta-human

chorionic gonadotropin [beta-hCG]) test/value at Screening. Patients who are

postmenopausal or permanently sterilized can be considered as not having reproductive

potential.

- WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted

reproduction during the entire trial, until 6 months after last BNT411 treatment.

- A man who is sexually active with a woman of childbearing potential and has not had a

vasectomy must agree to use a barrier method of birth control, e.g., either condom

with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap

(diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository,

and all men must also not donate sperm during the trial and for 6 months after

receiving the last dose of BNT411.

- All patients must provide an FFPE (Formalin Fixed Paraffin Embedded) from the latest

available archival tumor tissue. If such tissue cannot be provided, the sponsor's

approval of enrollment is needed.

Exclusion Criteria:

Prior and Concomitant Therapy:

- Has received prior systemic therapy with a TLR7 agonist.

- Has been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or

tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever is longer) of the

start of trial treatment; immunotherapy/monoclonal antibodies within 3 weeks of the

start of trial treatment; any live vaccine within 4 weeks of the start of trial

treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6

weeks of the start of trial treatment.

- Receives concurrent systemic (oral or intravenous) steroid therapy >10 mg prednisone

daily or its equivalent for an underlying condition.

- Receives concurrent strong inhibitors or inducers of the cytochrome P450 enzymes.

- Has had major surgery within the 4 weeks before the first dose of BNT411.

- Has ongoing or active infection requiring intravenous treatment with anti-infective

therapy that has been administered less than two weeks prior to first dose of trial

treatment.

- Has side effects of any prior therapy or procedures for any medical condition not

recovered to NCI CTCAE v.5 grade ≤1.

- Has any contraindication to atezolizumab, carboplatin or etoposide as per USPI or SmPC

in Part 1B.

Medical Conditions

- Current evidence of new or growing brain or leptomeningeal metastases during

screening. Patients with known brain or leptomeningeal metastases may be eligible if

they:

1. had radiotherapy, surgery or stereotactic surgery for the brain or leptomeningeal

metastases,

2. have no neurological symptoms (excluding Grade ≤2 neuropathy),

3. have stable brain or leptomeningeal disease on the CT or MRI scan within 4 weeks

before signing the informed consent,

4. are not undergoing acute corticosteroid therapy or steroid taper.

- Has history of seizures other than isolated febrile seizure in childhood; has a

history of a cerebrovascular accident or transient ischemic attack less than 6 months

ago.

- Has effusions (pleural, pericardial, or ascites) requiring drainage.

- Has eye pathology likely to confound observation of potential ocular AEs.

- Has a fever ≥38°C within 3 days before signing the ICF.

- Has a history of autoimmune disease active or past including but not limited to

inflammatory bowel disease, systemic lupus erythematosus (SLE), ankylosing

spondylitis, scleroderma, or multiple sclerosis. Has any active immunologic disorder

requiring immunosuppression with steroids or other immunosuppressive agents (e.g.,

azathioprine, cyclosporine A) with the exception of patients with isolated vitiligo,

resolved childhood asthma or atopic dermatitis, controlled hypoadrenalism or

hypopituitarism, and euthyroid patients with a history of Grave's disease. Patients

with controlled hyperthyroidism must be negative for thyroglobulin, thyroid peroxidase

antibodies, and thyroid-stimulating immunoglobulin prior to trial drug administration.

- Known history of seropositivity for human immunodeficiency virus (HIV) with CD4+

T-cell (CD4+) counts <350 cells/uL and with a history of acquired immunodeficiency

syndrome (AIDS)-defining opportunistic infections.

- Known history/positive serology for hepatitis B requiring active anti-viral therapy

(unless immune due to vaccination or resolved natural infection or unless passive

immunization due to immunoglobulin therapy). Patients with positive serology must have

Hepatitis B virus (HBV) viral load below the limit of quantification.

- Active Hepatitis C virus (HCV) infection; patients who have completed curative

antiviral treatment with HCV viral load below the limit of quantification are allowed.

- Has a known hypersensitivity to a component of BNT411 drug product, or another similar

compound.

- Has another primary malignancy that has not been in remission for at least 2 years,

with the exception of those with a negligible risk of metastasis or death (such as

adequately treated carcinoma in situ of the cervix, basal or squamous cell skin

cancer, localized prostate cancer, or ductal carcinoma in situ).

Other Comorbidities

- Has abnormal electrocardiograms (ECGs) that are clinically significant, such as

Framingham-corrected QT interval >480 ms.

- In the opinion of the treating investigator, has any concurrent conditions that could

pose an undue medical hazard or interfere with the interpretation of the trial

results; these conditions include, but are not limited to:

1. ongoing or active infection requiring antibiotic/antiviral/antifungal therapy,

2. concurrent congestive heart failure (New York Heart Association [NYHA] Functional

Classification Class III or IV),

3. concurrent unstable angina,

4. concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial

fibrillation),

5. acute coronary syndrome within the previous 6 months,

6. significant pulmonary disease (shortness of breath at rest or on mild exertion)

for example due concurrent severe obstructive pulmonary disease.

- Has a cognitive, psychological or psychosocial impediment that would impair the

ability of the patient to receive therapy according to the protocol or adversely

affect the ability of the patient to comply with the informed consent process,

protocol, or protocol-required visits and procedures.

- Is pregnant or breastfeeding.

Studien-Rationale

Primary outcome:

1. Incidence of DLTs (Time Frame - 21 Days):
Occurrence of DLTs within a patient during the DLT evaluation period

2. Incidence of TEAEs (Time Frame - up to 2 Years):
Occurrence of treatment-emergent adverse events (TEAE) within a patient

3. Incidence of IMP dose reductions (Time Frame - up to 2 Years):
Occurrence of dose reduction of IMP within a patient due to treatment-emergent adverse events (TEAE)

4. Incidence of IMP treatment discontinuations due to toxicity (Time Frame - up to 2 Years):
Occurrence of discontinuation of IMP within a patient due to treatment-emergent adverse events (TEAE)

Secondary outcome:

1. Maximum Plasma Concentration (Cmax) of PK assessments (Time Frame - up to 2 Years)

2. Area under the curve (AUC) of PK assessments (Time Frame - up to 2 Years)

3. Objective Response Rate (ORR) (Time Frame - up to 2 Years):
ORR defined as the proportion of patients in whom a CR or PR is observed as best overall response; according to RECIST 1.1

4. Disease Control Rate (DCR) (Time Frame - up to 2 Years):
DCR defined as the proportion of patients in whom a CR or PR or SD (assessed at least 6 weeks after first dose) is observed as best overall response; according to RECIST 1.1

5. Duration of Response (DOR) (Time Frame - up to 2 Years):
DOR defined as the time from first objective response (CR or PR) to the date of the first occurrence of objective tumor progression (PD); according to RECIST 1.1

Studien-Arme

  • Experimental: Part 1A - monotherapy dose escalation
    BNT411 monotherapy
  • Experimental: Part 1B combination dose escalation
    BNT411 in combination with atezolizumab, carboplatin and etoposide
  • Experimental: Part 2 expansion cohorts
    BNT411 either as monotherapy or in combination with other anti-cancer agents

Geprüfte Regime

  • BNT411:
    intravenous
  • Atezolizumab:
    intravenous
  • Carboplatin:
    intravenous
  • Etoposide:
    intravenous

Quelle: ClinicalTrials.gov


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