Thermosome GmbH, a clinical-stage drug development company focused on targeted tumor therapies, today announced new, encouraging data from its ongoing Phase I 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 I 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 median 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 I setting.

At dose level 2 (40 mg/m²), the mean PFS reached 7.1 months. Two out of three participants in this dose level achieved a partial response (PR) according to Choi criteria and completed the maximum extended treatment phase of 12 cycles (~8.3 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 I 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 II 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.”

“It is exciting to see the promising results of THE001 combined with regional hyperthermia, demonstrating strong potential to address the high unmet need for better treatments for soft tissue sarcoma,” 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 II, also including the U.S., would offer a much-needed validation of this 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 on the back of the orphan drug designation granted by the FDA.”

Considering supportive feedback from the German 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.