Chemotherapy-naïve extensive-stage small cell lung cancer MedDRA version: 21.1 Level: PT Classification code 10041068 Term: Small cell lung cancer extensive stage System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
BioNTech Small Molecules GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For Part 1A: 1. 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: 2. Histologically or cytologically confirmed extensive stage small cell lung cancer (ES-SCLC)(per the Veterans Administration Lung Study Group [VALG] staging system) who received no prior chemotherapy for extensive stage disease. 3. 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. 4. No interstitial lung disease or active, non-infectious pneumonitis. For Both Part 1A and Part 1B 5. Male and female = 18 years of age. 6. Must sign an 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. Albumin level at screening =3 mg/dL. 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 10^9/L, b. 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 (GMCSF) to achieve these WBC and ANC levels), c. Platelet count =100 x 10^9/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) =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; multiplied by 0.742 if the patient is female; multiplied by 1.212, if the patient is African-American. 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 (See section 10.4 of the protocol) 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. ei
Exclusion criteria
Exclusion criteria: 1. Has received prior systemic therapy with a TLR7 agonist. 2. 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; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of trial treatment. 3. Receives concurrent systemic (oral or intravenous) steroid therapy >10 mg prednisone daily or its equivalent for an underlying condition. 4. Receives concurrent strong inhibitors or inducers of the cytochrome P450 enzymes. 5. Has had major surgery within the 4 weeks before the first dose of BNT411 6. 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. 7. Has side effects of any prior therapy or procedures for any medical condition not recovered to NCI CTCAE v.5 Grade =1 8. Current evidence of new or growing brain or leptomeningeal metastases during screening. Patients with known brain or leptomeningeal metastases may be eligible if they: a. had radiotherapy, surgery or stereotactic surgery for the brain or leptomeningeal metastases, b. have no neurological symptoms (excluding Grade =2 neuropathy), c. have stable brain or leptomeningeal disease on the CT or MRI scan within 4 weeks before signing the informed consent, d. are not undergoing acute corticosteroid therapy or steroid taper. 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 eye pathology likely to confound observation of potential ocular AEs. 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 (see protocol for further details). 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 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. 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) 19. Has abnormal elect
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety profile and determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of BNT411 in a mixed population of patients with solid tumors.;Secondary Objective: To establish the PK profile and evaluate the anti-tumor activity of BNT411 according to RECIST 1.1.;Primary end point(s): -Occurrence of dose limiting toxicities (DLTs) within a patient during the DLT evaluation period -Occurrence of treatment-emergent adverse events (TEAEs) within a patient including grade =3, serious, fatal TEAE by relationship -Occurrence of dose reduction and discontinuation of IMP within a patient due to treatment emergent adverse events (TEAE) -MTD –defined as the highest tolerated dose -Recommended phase 2 dose (RP2D) based on integrated evaluation of safety, tolerability, clinical benefit, Pharmacokinetic (PK), and Pharmacodynamic (PD) data, for all dose levels tested.;Timepoint(s) of evaluation of this end point: DLTs-during the DLT evaluation period (cycle 1: 21 days) TEAE occurrence- from the first dose of BNT411 until the safety follow-up visit. Occurrence of dose reduction and discontinuation of IMP within a patient due to treatment emergent adverse events (TEAEs) will be assessed from the first dose of BNT411 until the safety follow-up visit. MTD-at the end of Part 1A and Part 1B. RP2D-at the end of Part 1A and Part 1B. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -PK parameters (AUC, CL and VD, Cmax, Tmax, Ctrough, and T1/2) -Objective response rate (ORR) defined as the proportion of patients in whom a complete response (CR) or partial response (PR) is observed as best overall response. -Disease control rate (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. -Duration of response (DOR);Timepoint(s) of evaluation of this end point: PK parameters-ongoing basis detailed in the schedule of PK sampling provided in table 1-3 (Part 1A) and table 1-4 (Part 1B) of the protocol. ORR- Efficacy will be assessed by on-treatment imaging at Week 6 (+7 days), every 6 weeks (±7 days) for 48 weeks, and every 12 weeks (±7 days) thereafter until disease progression is assessed by the investigator. DCR-at least 6 weeks after first dose until end of safety follow-up visit. DOR-From the time of occurrence from first objective response (CR or PR) to the date of the first occurrence of objective tumor progression or death from any cause, whichever occurs first. | — |
Countries
Germany, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
BioNTech Small Molecules GmbH
Outcome results
None listed