Dose-escalating Trial With UniCAR02-T Cells and PSMA Target Module (TMpPSMA) in Patients With Progressive Disease After Standard Systemic Therapy in Cancers With Positive PSMA Marker

Exclusion Criteria

• •1. Central nervous system metastasis or meningeosis carcinomatosa
• •2. Cardiac disease: i.e. heart failure (NYHA III or IV); unstable coronary artery disease, myocardial infarction or serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy within the last 6 months prior to study entry
• •3. Patients undergoing renal dialysis
• •4. Pulmonary disease with clinical relevant hypoxia (need for oxygen inhalation)
• •5. Parkinson, epilepsy and stroke or presence or history of seizures, paresis, aphasia, central nervous system (CNS) or intracranial hemorrhage
• •6. History or presence of disseminated intravascular coagulation (DIC) or thromboembolism within the last three months
• •7. Multiple sclerosis
• •8. Hemolytic anemia
• •9. Eye diseases with neovascularization
• •10. Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
• •11. Presence of urotoxicity from previous chemo- or radiotherapy or urinary outflow obstruction
• •12. Vaccination with live viruses less than 2 weeks prior lymphodepletion therapy
• •13. Any disease requiring immunosuppressive therapy
• •14. Major surgery within 28 days (prior start of TMpPSMA infusion)
• •15. Other malignancy requiring active therapy but adjuvant endocrine therapy is allowed
• •16. Treatment with any investigational drug substance or experimental therapy within 4 weeks or 5 half-lives of the substance (whatever is shorter) prior to administration of TMpPSMA
• •17. Prior treatment with gene therapy products
• •18. Use of checkpoint inhibitors within 5 half-lives of the respective substance prior to administration of TMpPSMA
• •19. Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants (note that physiologic steroid replacement not exceeding 10 mg prednisolone equivalent per day is allowed)
• •20. Psychologic disorders, drug and/or significant active alcohol abuse
• •21. Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
• •22. Presence of autoantibodies against La/SS-B or presence or history of autoimmune diseases (e.g. systemic lupus erythematosus, SS/SLE overlap syndrome, subacute cutaneous lupus erythematosus, neonatal lupus, primary biliary cirrhosis, Sjögren's syndrome)
• •23. Known hypersensitivity to cellular component (UniCAR02-T) and/or targeting peptide module (TMpPSMA) excipients and/or contraindication to compounds of the lymphodepletion therapy (cyclophosphamide and fludarabine), and tocilizumab or corticosteroids as specified in the respective IB/SmPC
• •24. Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance)
• •25. Incapability of understanding purpose and possible consequences of the trial
• •26. Patients who should not be included according to the opinion of the investigator