JOURNAL ONKOLOGIE – STUDIE

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

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04633148

Studienbeginn:
November 2020

Letztes Update:
08.01.2021

Wirkstoff:
Cyclophosphamide (Non-IMP), Fludarabine (Non-IMP), UniCAR02-T-pPSMA, UniCAR02-T (IMP)

Indikation (Clinical Trials):
Kidney Neoplasms, Disease Progression

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Cellex Patient Treatment GmbH

Collaborator:
PHARMALOG Institut für klinische Forschung GmbH

Studienleiter

Ralf Bargou, Prof.
Principal Investigator
Wuerzburg University Hospital

Kontakt

Antje Schubert, Dr.
Kontakt:
Phone: +493514466450
E-Mail: UC02-PSMA-01@cellex-treatment.me» Kontaktdaten anzeigen

Martin Lorkowski
Kontakt:
Phone: +493514466450
E-Mail: UC02-PSMA-01@cellex-treatment.me» Kontaktdaten anzeigen

Studienlocations (3 von 3)

Leberkrebszentrum Universitätsklinikum Ulm
Albert-Einstein-Allee 23
89081 Ulm
DeutschlandRekrutierend» Google-Maps
Ansprechpartner:
Andreas Viardot, Prof.
E-Mail: andreas.viardot@uniklinik-ulm.de» Ansprechpartner anzeigen

Onkologisches Zentrum Universitätsklinikum Würzburg
Josef-Schneider-Straße 6
97080 Würzburg
DeutschlandRekrutierend» Google-Maps
Ansprechpartner:
Ralf Bargou, Prof.
E-Mail: Bargou_R@ukw.de» Ansprechpartner anzeigen

Universitätsklinikum Dresden
01307 Dresden
(Sachsen)
GermanyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Martin Wermke, Dr. med
E-Mail: martin.wermke@uniklinikum-dresden.de» Ansprechpartner anzeigen

Studien-Informationen

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

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Safety and tolerability (Time Frame - DLT period (infusion period of TMpPSMA + 14 days or + 21 days in patients with with myelosuppression)):
Incidence and intensity of adverse events graded according to CTCAE V5.0

2. Incidence of dose limiting toxicity (DLT) (Time Frame - DLT period (infusion period of TMpPSMA + 14 days or + 21 days in patients with with myelosuppression)):
DLT is defined as any adverse Event at least possible related to TMpPSMA and/or UniCAR02-T

3. Maximum tolerated dose (MTD) (Time Frame - DLT period (infusion period of TMpPSMA + 14 days or + 21 days in patients with with myelosuppression)):
The dose for which the isotonic estimate of the DLT probability is closest to the target DLT probability of 0.2.

Secondary outcome:

1. Recommended phase 2 dose (RP2D) (Time Frame - DLT period (infusion period of TMpPSMA + 14 days or + 21 days in patients with with myelosuppression)):
The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.

2. Antitumor activity (Time Frame - DLT period (infusion period of TMpPSMA + 14 days or + 21 days in patients with with myelosuppression)):
Antitumor activity of UniCAR02-T-pPSMA at any time point according to RECIST 1.1 (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)

3. Prostate specific antigen (PSA) response in prostate cancer (Time Frame - DLT period (infusion period of TMpPSMA + 14 days or + 21 days in patients with with myelosuppression))

4. Overall Survival (OS) (Time Frame - Until fifteen years after last UniCAR02-T administration)

Geprüfte Regime

Cyclophosphamide (Non-IMP):
Intravenous infusion for 3 days
Fludarabine (Non-IMP):
Intravenous infusion for 3 days
UniCAR02-T-pPSMA:
Intravenous Infusion for 24 days
UniCAR02-T (IMP):
Intravenous infusion of single dose

Quelle: ClinicalTrials.gov