First Objective: to determine whether TIL-ACT using IL-2 analogue ANV419 reduces the frequency of Grade 2-4 toxicities (based on Common Terminology Criteria for Adverse Events v5.0 - CTCAE v5.0) which are associated to the study therapy and which are non-haematological events by at least 35% as compared to TIL-ACT using HD-IL-2. In case this objective is achieved, the co-primary objective will be to assess the non-inferiority of ANV419 vs HD-IL-2 in overall survival rate at 1 year (OS-1y) after TIL infusion.
Status of the objective
To progress in this objective, we conducted all essential clinical trial preparations:
- Agreement on IMPD submission strategy
- Clinical Trial Design & Documentation:
- Created comprehensive trial documents including the protocol, IMPD, patients' information sheets, investigator brochure, and pharmacy and laboratory manuals.
Approval Process:
Submitted through CTIS and achieved approvals in Denmark, the Netherlands, and Spain. Sweden will be included at a later stage, once they receive approval of their new IMPD.
For this, it was crucial to reach agreements in two key areas: (i) the clinical trial design and toxicity evaluation, and (ii) the IMPD submission strategy.
Second Objective: to compare quality of life (QoL) of patients during their hospitalization period, using ANV419 vs HD-IL-2. To measure patient QoL, we will use several standardized QoL questionnaires that were selected with patients representatives. Additionally, we plan to capture and compare short and long-term measurements of treatment-related toxicities focusing on key QoL domains co-defined by patients and healthcare providers (HCPs). This objective will include the collection of QoL and treatment toxicity data using validated patient-reported outcomes and passively sensed data via wearable technology. In addition, an in-depth qualitative evaluation of patient experience will be performed.
Status of the Objective
- Patient Advisory Committee
During PragmaTIL’s first reporting period several actions related to the second objective have taken place, coordinated by WP3 and WP1 leaders. In M3 a Patient Advisory Committee (PAC) was created, including six patient representatives from different participating countries (Spain, Israel, Denmark, Netherlands). The aim of the PAC is to inegrate the patient perspective, voice and needs into the trial design and activities to make the trial as well-designed and effective for patients and HCPs as possible. The PAC and experiential expertise of HCP and patients within the PAC has been and will continue to be leveraged at key points throughout the trial pathway (protocol development, trial execution, results communication).
The PAC participation has been organized by workshops following the System Oriented Dialogue Model (SODM). The PAC has held a total of 4 workshops.
- PRO Selection
Within the second objective, one of the main tasks has been the selection of measures of treatment related toxicities and QoL through the selection of patient reported outcomes (PRO) questionnaires. PRO measurement needs were identified after a complete literature review and collaboration with the PAC to understand key QoL domains and important toxicities. After further discussion with WP3 and WP1 participants, a final chart of PRO measures and validated questionnaires were selected to measure QoL in the PragmaTIL clinical trial. Patients will also participate in qualitative interviews to provide a more in-depth understanding of the patient experience in this clinical trial. A standard interview guide has been developed to guide qualitative interviews. All information regarding the PRO selection is described in the progress report of WP3.
Third Objective: to develop the health technology assessment (HTA) of TIL-ACT using ANV419, via the analysis of cost-effectiveness, budget impact, reimbursement strategies, user acceptance, and technical feasibility.
Status of the Objective
The work regarding this objective has partially started. To achieve this objective, we need the clinical trial to have concluded.
