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

NCT04633148 | Terminated Phase 1 DMC

• 2 other identifiers: UC02-PSMA-012019-004211-32
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

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

Outcome Measures

Primary Outcomes (3)

• 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)

• 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)

• 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 Outcomes (5)

• Recommended phase 2 dose (RP2D)

  DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)

• Antitumor activity

  DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)

• Prostate specific antigen (PSA) response

  DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)

• Overall Survival (OS)

  Until fifteen years after last UniCAR02-T administration

• Influence on Circulating tumor cells (CTC)

  Before start of lymphodepletion therapy until 6 resp. 12 months after start of last TMpPSMA application

Study Arms (1)

UniCAR02-T-pPSMA

EXPERIMENTAL

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.

Drug: Cyclophosphamide (Non-IMP); Drug: Fludarabine (Non-IMP); Drug: UniCAR02-T-pPSMA; Drug: UniCAR02-T (IMP)

Interventions

Cyclophosphamide (Non-IMP) DRUG

Intravenous infusion for 3 days

UniCAR02-T-pPSMA

Fludarabine (Non-IMP) DRUG

Intravenous infusion for 3 days

UniCAR02-T-pPSMA

UniCAR02-T-pPSMA DRUG

Intravenous Infusion for 21 days

UniCAR02-T-pPSMA

UniCAR02-T (IMP) DRUG

Intravenous infusion of single dose

UniCAR02-T-pPSMA

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Central nervous system metastasis or meningeosis carcinomatosa
• 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
• Patients undergoing renal dialysis
• 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
• Multiple sclerosis
• Hemolytic anemia
• Eye diseases with neovascularization
• Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
• Presence of urotoxicity from previous chemo- or radiotherapy or urinary outflow obstruction
• Vaccination with live viruses less than 2 weeks prior lymphodepletion therapy
• Any disease requiring immunosuppressive therapy
• Major surgery within 28 days (prior start of TMpPSMA infusion)
• Other malignancy requiring active therapy but adjuvant endocrine therapy is allowed

Sponsors & Collaborators

• AvenCell Europe GmbH: lead
• PHARMALOG Institut für klinische Forschung GmbH: collaborator

Study Sites (4)

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Universitätsklinikum Würzburg

Würzburg, Bavaria, 97080, Germany

Location

Universitätsklinikum Dresden

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Cyclophosphamide; fludarabine; Inosine Monophosphate

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Inosine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Officials

• Ralf Bargou, Prof.

  Wuerzburg University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Initial dose escalation followed an adaptive design. Further dose escalation includes 2 additional TMpPSMA dose levels and follows a 3+3 design.

Study Record Dates

• First Submitted: November 11, 2020
• First Posted: November 18, 2020
• Study Start: November 23, 2020
• Primary Completion: March 28, 2024
• Study Completion: March 28, 2024
• Last Updated: April 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4)