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

NCT ID: NCT04633148

Last Updated: 2024-04-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-23
• Study Completion Date: 2024-03-28

Brief Summary

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

UniCAR02-T-pPSMA

Preconditioning (lymphodepletion) with cyclophosphamide and fludarabine, followed by combination treatment of genetically modified T-cells carrying universal chimeric antigen receptors (UniCAR02-T) with the peptide TMpPSMA.

Group Type: EXPERIMENTAL

Cyclophosphamide (Non-IMP)

Intervention Type: DRUG

Intravenous infusion for 3 days

Fludarabine (Non-IMP)

Intervention Type: DRUG

Intravenous infusion for 3 days

UniCAR02-T-pPSMA

Intervention Type: DRUG

Intravenous Infusion for 21 days

UniCAR02-T (IMP)

Intervention Type: DRUG

Intravenous infusion of single dose

Interventions

Cyclophosphamide (Non-IMP)

Intravenous infusion for 3 days

Intervention Type: DRUG

Fludarabine (Non-IMP)

Intravenous infusion for 3 days

Intervention Type: DRUG

UniCAR02-T-pPSMA

Intravenous Infusion for 21 days

Intervention Type: DRUG

UniCAR02-T (IMP)

Intravenous infusion of single dose

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years

2. Patients diagnosed with progressive castration-resistant prostate cancer refractory to standard treatments and with no other available standard or curative treatment

3. Measurable or non-measurable disease based on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) and positivity in PSMA Positron Emission Tomography (PET)

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

5. Life expectancy of at least 3 months

6. Adequate renal and hepatic laboratory assessments

7. Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF)

8. Permanent venous access existing (e.g. port-system) resp. acceptance of implantation of a device

9. Able to give written informed consent

10. Weight ≥ 45kg

11. Using a highly effective method of birth control

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

PHARMALOG Institut für klinische Forschung GmbH

UNKNOWN

Sponsor Role: collaborator

AvenCell Europe GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralf Bargou, Prof.

Role: PRINCIPAL_INVESTIGATOR

Wuerzburg University Hospital

Locations

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Universitätsklinikum Würzburg

Würzburg, Bavaria, Germany

Universitätsklinikum Dresden

Dresden, Saxony, Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Countries

Germany

Other Identifiers

2019-004211-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UC02-PSMA-01

Identifier Type: -

Identifier Source: org_study_id