Thermosome, a Munich-based drug development company specializing in targeted tumor therapies, has received approval from the German Federal Institute for Drugs and Medical Devices (BfArM) and the responsible Ethics Committee to conduct a Phase 1 trial of its lead program THE001 in patients with soft tissue sarcoma.
The open-label, interventional dose-escalation study will begin enrolling patients in the second quarter of 2023 at two specialized clinical sites in Germany: Helios Klinikum Berlin-Buch and LMU Klinikum in Munich. PD Dr. Peter Reichardt, a recognized sarcoma and hyperthermia expert at Helios Klinikum Berlin-Buch, will serve as the Principal Investigator.
Novel Thermosensitive Technology
THE001 represents a significant advancement in targeted cancer therapy, utilizing a thermosensitive liposomal formulation of doxorubicin (DPPG2-TSL-DOX). Unlike conventional liposomal drugs, Thermosome's proprietary technology enables intravascular drug release triggered by mild heat applied using clinically established hyperthermia devices.
This innovative approach can generate up to 15-fold higher local drug concentrations at the tumor site, potentially overcoming drug resistance by reaching less well-perfused areas. Conventional doxorubicin administration cannot achieve these concentrations due to systemic toxicity limitations.
"We know from preclinical studies in soft tissue sarcoma that our approach results in significantly improved local efficacy by providing a local boost at the desired site of action," explained Dr. Pascal Schweizer, co-founder and CEO/CFO of Thermosome.
The company also anticipates that regional hyperthermia may induce an additive immune response, further enhancing treatment efficacy.
Trial Design and Objectives
The Phase 1 trial will focus primarily on evaluating the safety and tolerability of THE001 and determining the maximum tolerated dose. A secondary objective is to assess anti-tumor activity in patients with locally advanced unresectable or metastatic soft tissue sarcoma.
Following a standard 3+3 design, the compound will be administered at three dose levels, with three to six patients treated per dose level. This methodical approach will help establish the optimal dosing regimen for future studies.
Dr. Peter Reichardt expressed optimism about the trial: "I believe that Thermosome's approach has the potential to change the standard of care for locally advanced soft tissue sarcomas, and I am excited to evaluate THE001 in a clinical setting in an indication with such a high unmet medical need."
Addressing an Unmet Need in Soft Tissue Sarcoma
Soft tissue sarcoma (STS) represents a particularly challenging cancer type, affecting many young patients and occurring in more than 50 different subtypes. Locally advanced STS tumors are often large, invasive, and difficult or impossible to resect completely.
Current neoadjuvant therapy, used to shrink tumors preoperatively to enable curative surgery, relies on free doxorubicin in combination with ifosfamide or dacarbazine. While guidelines recommend combining doxorubicin-based therapy with regional hyperthermia, response rates remain below 30%, highlighting the significant unmet need for improved treatment options.
THE001 has received European Orphan Drug Designation for STS, recognizing the potential importance of this novel approach for patients with limited therapeutic options.
A Platform Approach to Targeted Cancer Therapy
Thermosome's technology represents a platform approach to targeted cancer therapy that functions independently of specific molecular targets. This characteristic potentially allows it to address patient populations across all tumor subtypes, offering a physically controlled targeting method rather than relying on biological targeting, which can be challenging given the heterogeneity of sarcomas.
While soft tissue sarcoma is the first clinical indication for THE001, the company's technology platform could potentially be applied to other difficult-to-treat solid tumors in the future.
The initiation of this first-in-human trial marks a significant milestone for Thermosome, representing years of preclinical development and the translation of a promising technology into clinical testing. The results will provide crucial insights into the safety, tolerability, and preliminary efficacy of this novel approach to targeted cancer therapy.
