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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04633148
• Other study ID #: UC02-PSMA-01
• Secondary ID: 2019-004211-32
• Status: Terminated
• Phase: Phase 1
• Start date: November 23, 2020
• Est. completion date: March 28, 2024

Study information

• Verified date: April 2024
• Source: AvenCell Europe GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: March 28, 2024
• Est. primary completion date: March 28, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Disease Progression
• Prostate Cancer

Intervention

Drug:
• Cyclophosphamide (Non-IMP)
Intravenous infusion for 3 days
• Fludarabine (Non-IMP)
Intravenous infusion for 3 days
• UniCAR02-T-pPSMA
Intravenous Infusion for 21 days
• UniCAR02-T (IMP)
Intravenous infusion of single dose

Locations

Country	Name	City	State
Germany	Universitätsklinikum Dresden	Dresden	Sachsen
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum Ulm	Ulm	Baden-Württemberg
Germany	Universitätsklinikum Würzburg	Würzburg	Bayern

Sponsors (2)

Lead Sponsor	Collaborator
AvenCell Europe GmbH	PHARMALOG Institut für klinische Forschung GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability	Incidence and intensity of adverse events graded according to CTCAE V5.0 with the exception of CRS and ICANS graded according to Lee et al. 2014 and Lee et al. 2019 respectively	DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Primary	Incidence of dose limiting toxicity (DLT)	DLT is defined as any adverse event at least possible related to TMpPSMA and/or UniCAR02-T	DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Primary	Maximum tolerated dose (MTD)	The dose for which the isotonic estimate of the DLT probability is closest to the target DLT probability of 0.2.	DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Secondary	Recommended phase 2 dose (RP2D)	The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.	DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Secondary	Antitumor activity	Antitumor activity of UniCAR02-T-pPSMA at any time point according to irRECIST (immune-related) Response Evaluation Criteria in Solid Tumors): Complete remission (CR) and partial remission (PR), Objective response rate (ORR), Disease control rate (DCR), Best response rate, Duration of response (DOR),Progression free survival (PFS)	DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Secondary	Prostate specific antigen (PSA) response		DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Secondary	Overall Survival (OS)		Until fifteen years after last UniCAR02-T administration
Secondary	Influence on Circulating tumor cells (CTC)		Before start of lymphodepletion therapy until 6 resp. 12 months after start of last TMpPSMA application