Marc Peeters

Overview of adverse events (AE) reported during the study and assessed as related to TempoCure, whole-body hyperthermia or their combination, categorized by severity (CTCAE v5.0).

Representativeness of Study Participants

Patient demographics, clinical status, prior treatments (not chronologically sorted), cohort assignment, and screening outcomes for participants enrolled or screened in the MATTERS study.

Overview of SAEs reported during the study and assessed as related to TempoCure, WBHT, or their combination, categorized by severity (CTCAE v5.0).

AEs assessed as related to TempoCure, WBHT, or their combination and reported in three or more patients.

Distribution of related AEs and SAEs according to the duration of WBHT treatments.

Incidence of related AEs and SAEs observed during WBHT administered as monotherapy or in combination with chemotherapy.

Overview of adverse events (AE) reported during the study and assessed as related to TempoCure, whole-body hyperthermia or their combination, categorized by severity (CTCAE v5.0).

Purpose:Whole-body hyperthermia (WBHT) is a promising therapy for advanced malignancies, including metastatic pancreatic ductal adenocarcinoma (PDAC). This first-in-human study evaluated the safety and tolerability of repeated WBHT sessions at 41.50°C for various treatment durations and in combination with standard-of-care chemotherapy regimens.Patients and Methods:Twelve patients with advanced solid tumors, primarily metastatic PDAC, completed the study. WBHT was administered using an innovative medical device (TempoCure, ElmediX) as monotherapy or with standard-of-care chemotherapy in escalating durations of 2, 4, and 6 hours, in four cohorts. Safety was assessed through adverse event (AE) monitoring, serious AE (SAE) reporting, and comprehensive clinical and laboratory evaluations up to a 10-week follow-up. Tolerability was evaluated according to whether patients were able to complete all planned WBHT cycles, with or without concomitant chemotherapy, without the need for dose modifications or treatment interruptions.Results:The WBHT treatment was well tolerated, with most patients completing scheduled treatments despite advanced disease. The most frequent AEs were fatigue, hypokalemia, nausea, and diarrhea. Initial decubitus ulcers led to improved patient handling protocols. No clear increase in AE or SAE incidence was associated with longer WBHT durations or chemotherapy combination. The trend toward fewer AEs in later treatments likely reflects a procedural learning curve.Conclusions:WBHT administered with the TempoCure system at 41.50°C for 2, 4, and 6 hours is safe and tolerable alone or in combination with chemotherapy, in patients with advanced cancer refractory to prior treatments. These findings support further investigation in upcoming randomized trials designed to evaluate efficacy in metastatic PDAC.Significance:The MATTERS trial demonstrates that WBHT at 41.50°C, delivered with the TempoCure device, is a safe and well-tolerated treatment for advanced malignancies, particularly in patients with refractory metastatic PDAC. These findings support the integration of WBHT with standard chemotherapy regimens, paving the way for future efficacy trials aimed at improving therapeutic outcomes in challenging cancer populations.

Study design of MATTERS on WBHT dose-escalation and combination treatment in patients with metastatic cancer, with a focus on PDAC. This diagram depicts the MATTERS study, designed to evaluate the safety and tolerability of WBHT in patients with advanced cancer through sequential cohort escalation. In cohort A1, three patients with advanced solid tumors received WBHT monotherapy with increasing durations of 2, 4, and 6 hours. Cohort A2 included one patient who received three repeated WBHT sessions at a fixed intermediate duration of 4 hours to confirm safety and tolerability. Cohorts B and C enrolled patients with metastatic PDAC. In cohort B, patients received 2-hour WBHT sessions as monotherapy first and then combined with 50% and 100% doses of gemcitabine-based standard-of-care (SoC) chemotherapy.