WP1: Development and characterization of the medical product
(Lead by Miltenyi, Germany)
- Development of integrated, clinical grade, fully automated magnetic cell selection system consisting of GMPcompliant separation reagent, dedicated tubing set and software for separation of professional cross-presenting dendritic cells (XP-DC) using the CliniMACS ProdigyTM instrument.
- Define optimal conditioning regiments for the personalized immunotherapeutic cell medicinal product.
- Functional validation of the XP-DC as a medicinal product.
WP2: Validation of the treatment strategy and the medicinal product
(Lead by CNIC, Spain)
- Define the best preconditioning regimen for optimal immunogenicity by XP-DC.
- Establish optimal treatment strategies with XP-DC in model systems of prostate and ovarian cancer.
- Specify optimal immunization conditions against tumour antigens by preclinical transfer of human XP-DC in humanized mice.
- Provide relevant information for the IMPD dossier regarding safety, bioactivity and efficacy of the XP-DC product for WP3.
- Provide information to optimize the treatment dose and schedule in the clinical trial protocols in WP4 and WP5
WP3: Regulatory affairs and approval for the cell immunotherapy products (IMPD) and clinical trial dossiers
(Lead by RUMC, Netherlands)
The main objective of this work package is to compile clinical trial dossiers including IMPD for this novel XP-DC based treatment modality for prostate and ovarian cancer patients and the clinical trial protocols.
WP4: Dose finding, safety, immunogenicity and randomized efficacy assessment of XP-DC in prostate cancer patients in high risk of post-surgical relapse
(Lead by UNAV, Spain)
- Implementing bicentric clinical trial testing of XP-DC in a non-randomized, dose escalation cohort of prostate cancer patients (n=12-15) following prostatectomies with high risk of relapse. A safe and immunogenic dose (defined by response to a reporter antigen) will be chosen for cohort 2 and WP5 ovarian cancer clinical trial.
- Implementation of a 1:1 randomized phase II clinical trial of XP-DC versus observation in n=65 prostate cancer patients per arm at high risk of relapse following prostatectomy. Co-primary endpoints will be PSA levels (analytical relapse free survival), immune responses against endogenous tumour antigens and safety.
WP5: Safety confirmation, immunogenicity and efficacy assessment of XP-DC in platinum sensitive ovarian cancer patients with recurrent disease following secondary surgery
(Lead by CHUV, Switzerland)
- Implementation of a single arm, open labelled, bicentric phase IIa clinical trial in platinum sensitive recurrent ovarian cancer patients (n=44) following secondary abdominal surgery for relapsed disease.
- Achievement of co-primary end points: a) intra-patients comparison of progress in free survival intervals after first and second surgery, b) assessment immunogenicity against tumour antigens and safety.
WP6: Harmonized immunomonitoring tailored to the PROCROP clinical trials
(Lead by UNIL, Switzerland)
- Establish validated standard operating procedures for immunomonitoring across the PROCROP consortium.
- Assess immune responses in XP-DC ovarian and prostate cancer patients using harmonized assays.
- Exploring potential biomarkers predicting immune and clinical outcomes.
WP7 & 8: Project Coordination and Dissemination and exploitation management
(Lead by FIMA, Spain)
The main objective of this work package is to set up an effective management framework for the PROCROP consortium, which will ensure the correct progress of the project towards its planned objectives.