Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT411
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04101357|
Recruitment Status : Recruiting
First Posted : September 24, 2019
Last Update Posted : July 28, 2020
|First Submitted Date ICMJE||September 20, 2019|
|First Posted Date ICMJE||September 24, 2019|
|Last Update Posted Date||July 28, 2020|
|Actual Study Start Date ICMJE||June 19, 2020|
|Estimated Primary Completion Date||June 2022 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures
|Original Other Pre-specified Outcome Measures||Same as current|
|Brief Title ICMJE||Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT411|
|Official Title ICMJE||Phase 1/2a, First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety, PK, PD, 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 ES-SCLC|
|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 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||Not Provided|
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 1
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||December 2023|
|Estimated Primary Completion Date||June 2022 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
For Part 1A:
For Part 1B:
• Histologically or cytologically confirmed chemotherapy-naïve ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system).
For Both Part 1A and Part 1B 5. Male and female ≥ 18 years of age. 6. 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.
7. ECOG performance status of 0 to 1. 8. Measurable disease according to RECIST 1.1. 9. Able to receive the first administration of trial treatment within 42 days from the last documented disease progression.
10. Adequate coagulation function at Screening as determined by:
a. International normalized ratio (INR) or prothrombin time ≤1.5 x upper limit normal (ULN; unless on therapeutic anticoagulants with values within therapeutic window), b. Activated partial thromboplastin time (aPTT) ≤1.5 x ULN (unless on therapeutic anticoagulants with values within therapeutic window).
11. Adequate hematologic function at Screening as determined by:
a. White blood count (WBC) ≥3 x 109/L b. Absolute neutrophil count (ANC) ≥1.5 x 109/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) c. Platelet count ≥100 x 109/L d. Hemoglobin (Hgb) ≥9.0 g/dL (may not transfuse or use erythropoietin to obtain this Hgb level).
12. Adequate hepatic function at Screening as determined by:
a. Total bilirubin ≤ 1.5 mg/dL (or ≤ 2.0 mg/dL for patients with known Gilbert's syndrome) b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ALT) ≤2.5 x ULN; or ≤5 x ULN in patients with metastatic liver disease 13. 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; multiply it by 0.742 if the patient is female; multiply it by 1.212, if the patient is African-American (Levey et al., 1999).
14. Able to attend trial visits as required by the protocol. 15. 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 (Section 10.4) can be considered as not having reproductive potential.
16. 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.
17. 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 (refer Section 10.4 for information on effective contraceptive methods).
18. 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 approval of enrollment is needed.
Prior and Concomitant Therapy:
Medical Conditions 8. Current evidence of new or growing brain or spinal metastases during screening. Patients with known brain or spinal metastases may be eligible if they:
a. had radiotherapy, surgery or stereotactic surgery for the brain or spinal metastases, b. have no neurological symptoms (excluding Grade ≤2 neuropathy), c. have stable brain or spinal disease on the CT or MRI scan within 4 weeks before signing the informed consent, d. must not be undergoing acute corticosteroid therapy or steroid taper. Chronic steroid therapy is acceptable provided that the dose is stable for the last 14 days prior to screening (≤ 10 mg prednisone daily or equivalent), f.e. spinal bone metastases are allowed, unless imminent fracture or cord compression is anticipated.
Notes: Subjects with central nervous system symptoms should undergo a Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI) of the brain to exclude new or progressive brain metastases.
9. 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.
10. Has effusions (pleural, pericardial, or ascites) requiring drainage. 11. Has retinal detachment, current/history of anterior/intermediate/posterior uveitis (including Vogt-Koyanagi-Harada syndrome, , current keratitis, thyroid-associated orbitopathy, idiopathic orbital inflammation, ischemic retinopathy (including glaucoma associated retinopathy), retinal vascular disease (e.g retinal vein occlusion, retinal artery occlusion), severe non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), cataract (according to AREDS lens grading system >2) 12. Has a fever ≥38°C within 3 days before signing the ICF. 13. 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.
14. 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.
15. Known history/positive serology for hepatitis B requiring active antiviral 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.
16. Active Hepatitis C virus (HCV) infection; patients who have completed curative antiviral treatment with HCV viral load below the limit of quantification are allowed.
17. Has a known hypersensitivity to a component of BNT411 drug product, or another similar compound.
18. 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) Note: should be discussed with Medical Monitor in case of uncertainties.
Other Comorbidities 19. Has abnormal electrocardiograms (ECGs) that are clinically significant, such as QT prolongation >480 ms.
20. 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:
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||Germany, Spain, United Kingdom, United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT04101357|
|Other Study ID Numbers ICMJE||BNT411-01|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||
|Responsible Party||BioNTech SE ( BioNTech Small Molecules GmbH )|
|Study Sponsor ICMJE||BioNTech Small Molecules GmbH|
|Collaborators ICMJE||Not Provided|
|PRS Account||BioNTech SE|
|Verification Date||July 2020|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP