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

Trial details

Who runs it

AvenCell Europe GmbH

Trial code

NCT04633148

Record updated

2024. április 23.

Original description

This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug UniCAR02-T-pPSMA in patients with progressive disease after standard systemic therapy in castration-resistant prostate cancers with positive PSMA marker. The UniCAR02-T-pPSMA drug is a combination of a cellular component (UniCAR02-T) with a recombinant antibody derivative (TMpPSMA) which together forms the active drug.Read full original descriptionShow less

Multicenter, Open-label, Adaptive Design Phase I Trial With Genetically Modified T-cells Carrying Universal Chimeric Antigen Receptors (UniCAR02-T) in Combination With PSMA Peptide Target Module (TMpPSMA) for the Treatment of Patients With Progressive Disease After Standard Systemic Therapy in Cancers With Positive PSMA Marker

This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug UniCAR02-T-pPSMA in patients with progressive disease after standard systemic therapy in castration-resistant prostate cancers with positive PSMA marker. The UniCAR02-T-pPSMA drug is a combination of a cellular component (UniCAR02-T) with a recombinant antibody derivative (TMpPSMA) which together forms the active drug.

Inclusion: Age ≥ 18 years; Patients diagnosed with progressive castration-resistant prostate cancer refractory to standard treatments and with no other available standard or curative treatment; Measurable or non-measurable disease based on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) and positivity in PSMA Positron Emission Tomography (PET); Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy of at least 3 months; Adequate renal and hepatic laboratory assessments; Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF); Permanent venous access existing (e.g. port-system) resp. acceptance of implantation of a device; Able to give written informed consent; Weight ≥ 45kg; Using a highly effective method of birth control.

Exclusion: 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; Presence of urotoxicity from previous chemo- or radiotherapy or urinary outflow obstruction; Vaccination with live viruses less than 2 weeks prior lymphodepletion therapy; Major surgery within 28 days (prior start of TMpPSMA infusion); 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; Prior treatment with gene therapy products; Use of checkpoint inhibitors within 5 half-lives of the respective substance prior to administration of TMpPSMA; Pulmonary disease with clinical relevant hypoxia (need for oxygen inhalation); Parkinson, epilepsy and stroke or presence or history of seizures, paresis, aphasia, central nervous system (CNS) or intracranial hemorrhage; History or presence of disseminated intravascular coagulation (DIC) or thromboembolism within the last three months; Eye diseases with neovascularization; Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy; Any disease requiring immunosuppressive therapy; Other malignancy requiring active therapy but adjuvant endocrine therapy is allowed; Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants (note that physiologic steroid replacement not exceeding 10 mg prednisolone equivalent per day is allowed); Psychologic disorders, drug and/or significant active alcohol abuse; Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV); 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); 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; Central nervous system metastasis or meningeosis carcinomatosa; Patients undergoing renal dialysis; Multiple sclerosis; Hemolytic anemia; Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance); Incapability of understanding purpose and possible consequences of the trial; Patients who should not be included according to the opinion of the investigator.

ClinicalTrials.gov NCT04633148