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

Primary Purpose

Solid Tumor, Extensive-stage Small Cell Lung Cancer

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BNT411
Atezolizumab
Carboplatin
Etoposide
Sponsored by
BioNTech SE
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumor focused on measuring Solid Tumor, Extensive-stage Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Cedars-Sinai Medical CenterRecruiting
  • Northwestern Medical Faculty FoundationRecruiting
  • Prisma Health-Upstate Cancer InstituteRecruiting
  • University Medical Center Hamburg-Eppendorf - (Recruiting only for part 1B and part 2)
  • Universitaetsklinikum Koeln - (Recruiting only for part 1B and part 2)
  • Universitaetsmedizin der Johannes Gutenberg Universitat Mainz KoeR - (Recruiting only for part 1B and part 2)
  • Hospital Universitari Vall d'HebronRecruiting
  • Clinica Universidad de NavarraRecruiting
  • START Madrid - CIOCC. Grupo Hospital de Madrid (HM) - Centro Integral Oncologico Clara Campal (CIOCC)Recruiting
  • Hospital Universitario La Fe de ValenciaRecruiting
  • Edinburgh Cancer Research CentreRecruiting
  • Sarah Cannon Research InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Part 1A - monotherapy dose escalation

Part 1B - combination dose escalation

Part 2 - expansion cohorts

Arm Description

BNT411 monotherapy

BNT411 in combination with atezolizumab, carboplatin, and etoposide

BNT411 either as monotherapy or in combination with with atezolizumab, carboplatin, and etoposide

Outcomes

Primary Outcome Measures

Incidence of dose-limiting toxicities (DLTs)
Occurrence of DLTs within a patient during the DLT evaluation period
Incidence of TEAEs
Occurrence of treatment-emergent adverse events (TEAE) within a patient including Grade ≥3, serious, fatal TEAE by relationship
Incidence of investigational medicinal product (IMP) dose reductions
Occurrence of dose reduction of BNT411 within a patient due to TEAEs
Incidence of IMP treatment discontinuations due to toxicity
Occurrence of discontinuation of BNT411 within a patient due to TEAEs
Determination of maximal tolerated dose (MTD)
MTD defined as the highest tolerated dose
Determination of the recommended Phase 2 dose (RP2D)
RP2D based on integrated evaluation of safety, tolerability, clinical benefit, pharmacokinetic (PK), and pharmacodynamic data, for all dose levels tested

Secondary Outcome Measures

PK assessments: Area under the concentration time curve (AUC)
PK assessments: Clearance (CL)
PK assessments: Volume of distribution (VD)
PK assessments: Maximum Plasma Concentration (Cmax)
PK assessments: Time to Cmax (Tmax)
PK assessments: Trough concentration (Ctrough)
PK assessments: Terminal half-life (T1/2)
Objective Response Rate (ORR)
ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) is observed as best overall response; according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Disease Control Rate (DCR)
DCR defined as the proportion of patients in whom a CR or PR or stable disease (SD) (assessed at least 6 weeks after first dose) is observed as best overall response; according to RECIST 1.1
Duration of Response (DOR)
DOR defined as the time from first objective response (CR or PR) to the date of the first occurrence of objective tumor progression (progressive disease; PD) or death from any cause, whichever occurs first; according to RECIST 1.1

Full Information

First Posted
September 20, 2019
Last Updated
August 31, 2023
Sponsor
BioNTech SE
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1. Study Identification

Unique Protocol Identification Number
NCT04101357
Brief Title
Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT411
Official Title
Phase 1/2a, First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BNT411 as a Monotherapy in Patients With Solid Tumors and in Combination With Atezolizumab, Carboplatin and Etoposide in Patients With Chemotherapy-naïve Extensive-stage Small Cell Lung Cancer (ES-SCLC)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 19, 2020 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioNTech SE

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
Detailed Description
The first part of this trial is a FIH, open-label, dose-escalation trial studying BNT411 monotherapy in patients with different types of malignant solid tumors in order to determine the safety profile of BNT411. The second part aims to determine further the safety profile of BNT411 in combination with atezolizumab, carboplatin and etoposide in patients with ES-SCLC. The third part is the expansion phase to explore BNT411 further as a monotherapy or in combination with atezolizumab, carboplatin and etoposide in select tumor indications. Different treatment schedules and other indications may also be explored in Part 2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Extensive-stage Small Cell Lung Cancer
Keywords
Solid Tumor, Extensive-stage Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1A - monotherapy dose escalation
Arm Type
Experimental
Arm Description
BNT411 monotherapy
Arm Title
Part 1B - combination dose escalation
Arm Type
Experimental
Arm Description
BNT411 in combination with atezolizumab, carboplatin, and etoposide
Arm Title
Part 2 - expansion cohorts
Arm Type
Experimental
Arm Description
BNT411 either as monotherapy or in combination with with atezolizumab, carboplatin, and etoposide
Intervention Type
Drug
Intervention Name(s)
BNT411
Intervention Description
intravenous
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Intervention Description
intravenous
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
intravenous
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
intravenous
Primary Outcome Measure Information:
Title
Incidence of dose-limiting toxicities (DLTs)
Description
Occurrence of DLTs within a patient during the DLT evaluation period
Time Frame
21 Days after the first dose
Title
Incidence of TEAEs
Description
Occurrence of treatment-emergent adverse events (TEAE) within a patient including Grade ≥3, serious, fatal TEAE by relationship
Time Frame
up to 2 Years
Title
Incidence of investigational medicinal product (IMP) dose reductions
Description
Occurrence of dose reduction of BNT411 within a patient due to TEAEs
Time Frame
up to 2 Years
Title
Incidence of IMP treatment discontinuations due to toxicity
Description
Occurrence of discontinuation of BNT411 within a patient due to TEAEs
Time Frame
up to 2 Years
Title
Determination of maximal tolerated dose (MTD)
Description
MTD defined as the highest tolerated dose
Time Frame
Up to 2 Years
Title
Determination of the recommended Phase 2 dose (RP2D)
Description
RP2D based on integrated evaluation of safety, tolerability, clinical benefit, pharmacokinetic (PK), and pharmacodynamic data, for all dose levels tested
Time Frame
Up to 2 Years
Secondary Outcome Measure Information:
Title
PK assessments: Area under the concentration time curve (AUC)
Time Frame
up to 2 Years
Title
PK assessments: Clearance (CL)
Time Frame
up to 2 Years
Title
PK assessments: Volume of distribution (VD)
Time Frame
up to 2 Years
Title
PK assessments: Maximum Plasma Concentration (Cmax)
Time Frame
up to 2 Years
Title
PK assessments: Time to Cmax (Tmax)
Time Frame
up to 2 Years
Title
PK assessments: Trough concentration (Ctrough)
Time Frame
up to 2 Years
Title
PK assessments: Terminal half-life (T1/2)
Time Frame
up to 2 Years
Title
Objective Response Rate (ORR)
Description
ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) is observed as best overall response; according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time Frame
up to 2 Years
Title
Disease Control Rate (DCR)
Description
DCR defined as the proportion of patients in whom a CR or PR or stable disease (SD) (assessed at least 6 weeks after first dose) is observed as best overall response; according to RECIST 1.1
Time Frame
up to 2 Years
Title
Duration of Response (DOR)
Description
DOR defined as the time from first objective response (CR or PR) to the date of the first occurrence of objective tumor progression (progressive disease; PD) or death from any cause, whichever occurs first; according to RECIST 1.1
Time Frame
up to 2 Years
Other Pre-specified Outcome Measures:
Title
immune Objective Response Rate (iORR)
Description
iORR defined as the proportion of patients in whom an immune complete response (iCR) or immune partial response (iPR) is observed as best overall response; according to immune RECIST (iRECIST)
Time Frame
up to 2 Years
Title
immune Disease Control Rate (iDCR)
Description
iDCR defined as the proportion of patients in whom an iCR or iPR or immune stable disease (iSD) (assessed at least 6 weeks after first dose) is observed as best overall response; according to iRECIST
Time Frame
up to 2 Years
Title
immune Duration of Response (iDOR)
Description
iDOR defined as the time from first objective response (iCR or iPR) to the date of the first occurrence of objective tumor progression (immune confirmed progressive disease; iCPD); according to iRECIST
Time Frame
up to 2 Years
Title
Progression Free Survival (PFS) time
Description
PFS defined as the time from first dose of BNT411 to first occurrence of objective tumor progression (per RECIST 1.1), or death from any cause, whichever occurs first
Time Frame
up to 3 Years
Title
Overall Survival (OS) time
Description
OS defined as the time from first dose of BNT411 to death from any cause
Time Frame
up to 3 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: For Part 1A: Histologically confirmed solid tumor (cytology is allowed for non-small cell lung cancer [NSCLC], small cell lung cancer [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 limited-stage small cell lung cancer (LS-SCLC) should be treatment-free for at least 6 months since last chemo/radiotherapy. 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. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Measurable disease according to RECIST 1.1. Albumin level at screening ≥30 g/L. Adequate coagulation function at screening as determined by: International normalized ratio (INR) or prothrombin time ≤1.5 x upper limit normal (ULN; unless on therapeutic anticoagulants with values within therapeutic window), 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: White blood cell count (WBC) ≥3 x 10^9/L, 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), Platelet count ≥100 x 10^9/L, Hemoglobin (Hgb) ≥9.0 g/dL. Adequate hepatic function at screening as determined by: Total bilirubin ≤1.5 mg/dL (or ≤2.0 mg/dL for patients with known Gilbert's syndrome), 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 m^2 - 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 WOCBP 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 Formalin Fixed Paraffin Embedded (FFPE) sample 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 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5 Grade ≤1. Notes: peripheral neuropathy Grade ≤2 is allowed; alopecia of any grade is allowed. 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: had radiotherapy, surgery or stereotactic surgery for the brain or leptomeningeal metastases, have no neurological symptoms (excluding Grade ≤2 neuropathy), have stable brain or leptomeningeal disease on the computed tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the informed consent, are not undergoing acute corticosteroid therapy or steroid taper. Notes: Patients with central nervous system symptoms should undergo a CT scan or MRI of the brain to exclude new or progressive brain metastases. Spinal bone metastases are allowed, unless imminent fracture with cord compression is anticipated. 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 adverse events. 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/µL 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. Notes: Country-specific criteria for Germany - To confirm that a patient would be eligible, an active infection with HIV/Hepatitis B or C should be ruled out by serum blood test at screening. 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: ongoing or active infection requiring antibiotic/antiviral/antifungal therapy, concurrent congestive heart failure (New York Heart Association [NYHA] Functional Classification Class III or IV), concurrent unstable angina, concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial fibrillation), acute coronary syndrome within the previous 6 months, 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. Has any contraindication to atezolizumab, carboplatin or etoposide as per US prescribing information (USPI) or summary of product characteristics (SmPC) in Part 1B.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
BioNTech clinical trials patient information
Phone
+49 6131 9084
Ext
0
Email
patients@biontech.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
BioNTech Responsible Person
Organizational Affiliation
BioNTech SE
Official's Role
Study Director
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Individual Site Status
Recruiting
Facility Name
Northwestern Medical Faculty Foundation
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Name
Prisma Health-Upstate Cancer Institute
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Individual Site Status
Recruiting
Facility Name
University Medical Center Hamburg-Eppendorf - (Recruiting only for part 1B and part 2)
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Individual Site Status
Completed
Facility Name
Universitaetsklinikum Koeln - (Recruiting only for part 1B and part 2)
City
Koeln
ZIP/Postal Code
50937
Country
Germany
Individual Site Status
Completed
Facility Name
Universitaetsmedizin der Johannes Gutenberg Universitat Mainz KoeR - (Recruiting only for part 1B and part 2)
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
Clinica Universidad de Navarra
City
Madrid
ZIP/Postal Code
28022
Country
Spain
Individual Site Status
Recruiting
Facility Name
START Madrid - CIOCC. Grupo Hospital de Madrid (HM) - Centro Integral Oncologico Clara Campal (CIOCC)
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario La Fe de Valencia
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Individual Site Status
Recruiting
Facility Name
Edinburgh Cancer Research Centre
City
Edinburgh
ZIP/Postal Code
EH4 2XU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Sarah Cannon Research Institute
City
London
ZIP/Postal Code
W1G 6AD
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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