A study to investigate the novel agent BNT111 and cemiplimab in combination or as single agents in patients with late stage skin cancer that has not responded to other forms of treatment
- Conditions
- Melanoma (Stage III and IV)MedDRA version: 21.1Level: PTClassification code: 10025670Term: Malignant melanoma stage III Class: 100000004864MedDRA version: 21.1Level: PTClassification code: 10025671Term: Malignant melanoma stage IV Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-509513-36-00
- Lead Sponsor
- BioNTech SE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 184
Patients must sign the written ICF before any screening procedure., Patients with BRAF V600-positive tumor(s) should have received prior treatment with a BRAF inhibitor (alone or in combination with a MEK inhibitor)., Adequate bone marrow function as defined by hematological parameters: a) Absolute neutrophil count (ANC) =1.5× 10E9/L achieved without the use of granulocyte colony-stimulating factor (G-CSF). b) Hemoglobin =9.0 g/dL (5.59 mmol/L). No transfusion is allowed within 1 week prior to treatment initiation. c.) Platelet count =100× 10E9/L., Patients must have serum LDH =ULN., Patient should have adequate hepatic function, as determined by: a) aspartate aminotransferase (AST) =3× ULN; alanine aminotransferase (ALT) =3× ULN (regardless of liver involvement); b) serum bilirubin =1.5× ULN, except in patients with Gilbert's Syndrome who must have a total bilirubin <3 mg/dL., Patient should have adequate kidney function, assessed by the estimated glomerular filtration rate (eGFR) =30 mL/min using the chronic kidney disease epidemiology collaboration (CKD-EPI) equation., Patient should be stable with adequate coagulation, as determined by: a) international normalized ratio (INR) or prothrombin time =1.5× ULN (unless on therapeutic anticoagulants with values within therapeutic window), and b) activated partial thromboplastin time (aPTT) =1.5× ULN (unless on therapeutic anticoagulants with values within therapeutic window)., Patients must provide the following biopsy samples: a)All patients: must provide a tumor tissue sample (formalin fixed paraffin-embedded [FFPE] blocks/slides) from a fresh biopsy collected before Visit C1D1, or archival tissue. The archival tissue can be an FFPE block (not older than 3 years) or freshly cut slides (special storage conditions and immediate shipment to specialty lab are required), preferably derived from advanced disease stage. b) Patients at selected trial sites: After additional consent, patients should be amenable to pre-treatment and on-treatment PBMC sampling and optional biopsy. If amenable, patients should provide a PBMC sample and optionally a biopsy which contains tumor tissue after failure/stop of last prior trial treatment., Women of childbearing potential (WOCBP) must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) test at screening. Patients that are post-menopausal or permanently sterilized can be considered as not having reproductive potential. a) Female patients of reproductive potential must agree to use highly effective contraception during and for 6 months after the last trial drug administration., WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during trial starting at screening, during the trial and for 6 months after receiving the last trial 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 trial treatment., Patients must have an ECOG PS =1., Patients must be aged = 18 years on the date of signing the ICF., Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the trial., Patient
Patients must not be pregnant or breastfeeding., Current evidence of ongoing NCI-CTCAE (v5.0) Grade > 1 toxicity of prior therapies before the start of treatment, with the exception of hair loss, hearing loss, Grade 2 peripheral neuropathy, or laboratory abnormalities not considered clinical significant per investigator’s discretion, and those Grade 2 toxicities listed as permitted in other eligibility criteria., Patients who have a local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia) which requires systemic antibiotic treatment within 2 wks prior to the first dose of trial treatment., Patients who have had a splenectomy., Patients who have had major surgery (e.g., requiring general anesthesia) within 4 wks before screening, have not fully recovered from surgery, or have a surgery planned during the time of trial participation., 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 if they: a) had radiotherapy or another appropriate therapy for the brain or spinal bone metastases, b) have no neurological symptoms that can be attributed to the current brain lesions, c) have stable brain or spinal disease on the CT or MRI scan within 4 wks before randomization (confirmed by stable lesions on two scans at least 4 weeks apart, the second scan can be carried out during screening), d) do not require steroid therapy within 14 days before the first dose of trial treatment, e) spinal bone metastases are allowed, unless imminent fracture or cord compression is anticipated., History or current evidence of significant cardiovascular disease including, but not limited to: a) angina pectoris requiring anti-anginal medication, uncontrolled cardiac arrhythmia(s), severe conduction abnormality, or clinically significant valvular disease; b) QTc (F) prolongation >480 ms; c) arterial thrombosis or pulmonary embolism within =6 months before the start of treatment; d) myocardial infarction within =6 months before the start of treatment; e) pericarditis (any NCI-CTCAE grade), pericardial effusion (NCI-CTCAE Grade =2), non-malignant pleural effusion (NCI-CTCAE Grade =2) or malignant pleural effusion (NCI-CTCAE Grade =3) within =6 months before the start of treatment; f) Grade =3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria Class =II within =6 months before the start of treatment., Patients who have received a live vaccine within 28 days of planned start of trial therapy., Known hypersensitivity to the active substances or to any of the excipients., Presence of a severe concurrent illness or other condition (e.g., psychological, family, sociological, or geographical circumstances) that does not permit adequate follow-up and compliance with the protocol., Prior treatment with BNT111 and/or with cemiplimab., Patients must not have history of uveal, acral, or mucosal melanoma., Patients must have no ongoing or recent evidence (within the last 5 years) of significant autoimmune disease that required treatment with systemic immunosuppressive treatments which may pose a risk for irAEs. 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., Patients must have no known primary immunodeficienci
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method