Bildnachweis: Pexels, VC Magazin, Pixabay.
Thermosome GmbH, a clinical-stage drug development company focused on targeted tumor therapies, today announced new, encouraging data from its ongoing Phase 1 clinical trial evaluating its lead compound THE001 (DPPG2-TSL-DOX) in combination with regional hyperthermia (RHT) for the treatment of soft tissue sarcomas (STS). The Phase 1 study is assessing the safety, pharmacokinetics (PK), and preliminary efficacy of THE001 + RHT in participants with locally advanced unresectable or metastatic STS, who have exhausted all prior treatment options, including standard doxorubicin (DOX).
Despite the early stage of development and a small number of participants, signs of meaningful clinical activity have emerged. Among the heavily pre-treated participants – including patients pre-treated with DOX – the median progression-free survival (PFS) following treatment with THE001 + RHT reached 4.5 months across both dose levels (20 and 40 mg/m2). This exceeds the typical PFS of 2.7 to 3.5 months observed with first-line DOX therapy in treatment-naïve patients at DOX doses of 75 mg/m2, i.e., 2-4x higher than doses of THE001 applied in the Phase 1 setting.
At dose level 2 (40 mg/m2), two out of three participants achieved a partial response (PR)
according to Choi criteria and completed the maximum extended treatment phase of 12
cycles (~8.3 months) with a mean PFS of 7.1 months. Notably, one participant whose tumor was initially considered unresectable, could undergo surgical resection at the end of the extended study treatment. This participant showed a tumor shrinkage of -16% in the sum of target lesions, a partial response according to Choi criteria and no vital tumor cells in the resected target lesion.
Across dose levels 1 and 2, THE001 + RHT demonstrated a favorable safety profile. There were no dose-limiting toxicities or high-grade treatment-related adverse events that led to
treatment discontinuation, underscoring the good tolerability of THE001 in combination with RHT.
“These findings not only provide consistent proof of the galenic concept of heat-triggered,
largely complete DOX release from THE001, but also demonstrate clinical benefit in a highly
challenging patient population,” said Dr. Frank Hermann, Chief Medical Officer of
Thermosome. “We are particularly encouraged by the results of one participant who
underwent resection after 12 full treatment cycles with THE001 and regional hyperthermia
with no vital tumor cells found in the resected target lesion. These results clearly support
future exploration in the neoadjuvant setting.”
Alexander Eggermont, Professor of Clinical and Translational Immunotherapy, University
Medical Center, Utrecht, and a member of Thermosome ́s Clinical Advisory Board,
commented: “The Phase 1 data of THE001, a thermosensitive liposomal DOX, and regional
hyperthermia in heavily pre-treated DOX-experienced soft tissue sarcoma patients,
particularly from dose level 2, are very encouraging. These results demonstrate the clinical
potential of this highly innovative approach and provide the necessary foundation for
transitioning into Phase 2 proof-of-concept development. I am excited to support this
important work and look forward to advancing this promising therapy, which has the
potential to significantly improve outcomes for patients with soft tissue sarcoma,
particularly in the neoadjuvant setting.”
“I am excited by the promising results of THE001 combined with regional hyperthermia,
demonstrating strong potential to address the high unmet need for better soft tissue
sarcoma treatments,” added Prof. Shreyaskumar Patel, the Robert R. Herring Distinguished
Professor of Medicine and Medical Director of the Sarcoma Center at The University of Texas MD Anderson Cancer Center, Houston Texas, and a member of Thermosome’s Clinical
Advisory Board. “Expansion into Phase 2, also including the U.S., would offer a much-needed new therapeutic strategy for patients with STS. I look forward to supporting the
advancement of this innovative treatment option to improve outcomes for patients here in
the U.S. and globally, following the granted orphan drug designation by the FDA.”
Considering supportive feedback from the Federal Institute for Drugs and Medical Devices
(BfArM) on the development of THE001 + RHT in the neoadjuvant setting, the available data from last-line participants are intended to support further development in the neoadjuvant setting.
