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

• Status: Recruiting
• Trial end date: 2023-05-01
• Target enrollment: 0
• Participant gender: All

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 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cellex Patient Treatment GmbH
• Collaborator: PHARMALOG Institut für klinische Forschung GmbH
• Treatments: Cyclophosphamide; Fludarabine

Criteria

Inclusion Criteria:

1. Male or female patients, age ≥ 18 years

2. PSMA expression positive cancer (i.e. urogenital tract [renal, transitional cell, prostate], non-small cell lung, breast and colorectal cancer) refractory to standard treatments and with no other available standard or curative treatment

3. Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 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. Negative pregnancy; routinely 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 continuous 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

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