THE001 Receives Orphan Drug Designation for Soft Tissue Sarcoma

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The FDA has granted orphan drug designation to the doxorubicin-encapsulating thermosensitive liposome therapy THE001 (DPPG2-TSL-DOX) for the treatment of patients with soft tissue sarcoma.1

This designation is based on data from a phase 1 trial (NCT05858710) evaluating THE001 in patients with locally advanced, unresectable or metastatic soft tissue sarcoma.

“We see the United States [US] orphan drug designation as a strong regulatory validation of the potential of our innovative approach in soft tissue sarcoma,” Pascal Schweizer, PhD, co-founder, chief executive officer, and chief financial officer of Thermosome, the developer of THE001, stated in a news release. “This recognition, based on preclinical and early clinical data from our phase 1 study, marks an important milestone and is a further step into the US market—the world’s most important market for patent-protected drugs. In parallel, we are evaluating strategic partnerships to advance THE001 and fully realize its therapeutic potential.”

Previously, THE001 also received orphan drug designation from the European Medicines Agency.

THE001 is a thermosensitive liposomal formulation of doxorubicin with a unique mechanism of action compared with conventional liposome therapies. THE001 employs technology that uses a heat-triggered intravenous drug release via clinically established hyperthermia devices, resulting in up to 15-fold higher local drug concentrations in the tumor and a local boost at a desired site of action. These high local concentrations of the therapy are designed to overcome drug resistance and elicit effects that cannot be achieved by administering conventional doxorubicin due to its systemic toxicity profile.

The ongoing, open-label phase 1 trial is evaluating THE001 alone or in combination with regional hyperthermia in patients at least 18 years of age with heavily pretreated, locally advanced, unresectable or metastatic soft tissue sarcoma, including those who had been previously treated with conventional doxorubicin.2,3 Patients need to have progressive disease not amenable to surgery, measurable disease per RECIST 1.1 criteria, a tumor accessible for regional hyperthermia, an ECOG performance status of 0 to 2, and adequate hematologic, organ, and coagulation function.3

Patients are being treated with THE001 monotherapy at 20 mg/m2 (dose level [DL] 1), 40 mg/m2 (DL2), or 50 mg/m2 across 6 21-day cycles in the main phase of the trial to determine the maximum tolerated dose (MTD) and recommended phase 2 dose.2 From cycle 2 onward, patients simultaneously undergo regional hyperthermia. Dexrazoxane was given as supportive treatment to prevent cardiotoxicity.

The phase 1 trial is being conducted at 2 sites in Germany. Initial feasibility, safety, pharmacokinetics, and antitumor activity findings were presented at the 2024 CTOS Annual Meeting.

Among patients who received DL1 (n = 4), 1 had a best overall response of stable disease (SD) per both RECIST 1.1 and Choi criteria, 2 had best overall responses of progressive disease per both sets of criteria, and 1 was not evaluable for response. Among patients who received DL2 (n = 3), 1 had a best overall response of SD per RECIST 1.1 criteria and partial response per Choi criteria, and the 2 remaining patients had unavailable response data.

The study investigators noted that THE001 was well tolerated as monotherapy and in combination with regional hyperthermia at both studied dose levels, supporting the planned THE001 dose escalation to 50 mg/m2. At a data cutoff of October 30, 2024, the safety profile of the study treatment was consistent with that of doxorubicin. Two serious adverse effects (AEs; grade 3 anemia and grade 3 infection) were reported; both were deemed unrelated to study treatment. No suspected unrelated serious AEs or DLTs were reported, and the investigators did not attribute any AEs to the liposomal formulation or application of regional hyperthermia.

References

1. Thermosome receives U.S. orphan drug designation for lead compound THE001, expands patent estate. News release. Thermosome. May 12, 2025. Accessed May 12, 2025. https://finance.yahoo.com/news/thermosome-receives-u-orphan-drug-080000546.html
2. Di Gioia D, Reichardt P, Güler SE, et al. Phase I study of THE001 (DPPG²-TSL-DOX) combined with regional hyperthermia in patients with locally advanced or metastatic soft tissue sarcoma. Presented at: 2024 CTOS Annual Meeting. November 13-16, 2024; San Diego, CA. Abstract P 410.
3. Study of DPPG2-TSL-DOX combined with hyperthermia in soft tissue sarcoma. ClinicalTrials.gov. Updated February 21, 2025. Accessed May 12, 2025. https://clinicaltrials.gov/study/NCT05858710