FDA Grants Orphan Drug Designation to Tigilanol Tiglate in Soft Tissue Sarcoma


The FDA has granted an orphan drug designation to tigilanol tiglate for the treatment of patients with soft tissue sarcoma.



The FDA has granted an orphan drug designation to the novel small molecule agent tigilanol tiglate (Stelfonta) as a potential therapeutic option for the treatment of patients with soft tissue sarcoma, according to an announcement from QBiotics Group Limited.1

“Soft tissue sarcomas constitute a rare group of tumors comprising more than 80 subtypes that affect both adults and children,” Victoria Gordon, PhD, executive director of Strategic Alliances and Investor Relations at QBiotics, said in a press release. “The prognosis of advanced soft tissue sarcoma patients remains unfavorable and new treatments are urgently needed. The FDA Orphan Drug Designation for tigilanol tiglate signals an important milestone for QBiotics, reflecting its recognition by the FDA as a potential new treatment option for this debilitating and life-threatening disease.”

In 2021, 124,573 new cases of soft tissue sarcoma were reported globally, with an annual incidence growth rate of 0.54%. Notably, it is projected that approximately 13,590 new cases of soft tissue sarcoma will be seen in 2024.1

The intratumoural injection is currently being evaluated in response to these unmet needs in the phase 2a QB46C-H07 trial (NCT05755113) for the treatment of patients with advanced and/or metastatic soft tissue sarcoma. The open-label, single-arm study aims to enroll approximately 10 adult patients with soft tissue sarcomas of the extremities and body wall who present with an ECOG performance status of 2 or less and have a life expectancy over 12 weeks.2

Eligible patients with unresectable tumors are permitted to receive up to a fixed-dose of 3.6 mg/m2 at 28-day intervals for up to a maximum of 5 treatments. Those who are eligible for surgery will receive a single intratumoral treatment with tigilanol tiglate. Surgery can be scheduled 28 days post-injection and in the case of a complete response (CR) following treatment, patients are monitored for recurrence.3

The primary end point of the phase 2a trial is tumor response; secondary end points consist of safety and pharmacokinetics. Other outcome measures include assessing changes in the tumor microenvironment, evaluation of peripheral blood mononucleocytes, and local recurrence rate at injection sites.2

Previously, in an Australian phase 1 study, tigilanol tiglate was evaluated in patients with accessible cutaneous, subcutaneous or nodal tumors refractory to conventional therapy. Patients were required to be over the age of 18, have an ECOG performance status of 2 or less, a life expectancy greater than 12 weeks, and measurable disease. Patients received tigilanol tiglate at a dose level up to 3.6 mg/m2. The coprimary end points of this study were safety, tolerability and maximum tolerated dose (MTD); secondary end points included preliminary efficacy and pharmacokinetics.4

The study enrolled 22 patients who were treated with tigilanol tiglate 0.06 mg/m2 (n = 1), 0.12 mg/m2 (n = 1), 0.24 mg/m2 (n = 4), 0.60 mg/m2 (n = 1), 1.20 mg/m2 (n = 1), 2.40 mg/m2 (n = 4), and 3.6 mg/m2 (n = 4), and 6 patients were enrolled to a local effect cohort that received an appropriate dose based on tumor size. In the overall population, the median age was 64 years (range, 31-86) and 68% were male. At enrollment, patients had AJCC stage IV, stage III, stage II and stage I disease (32%; 18%; 23%; 9%), respectively; 18% of patients had an unknown and/or not recorded disease stage.4

Efficacy findings demonstrated that 6 of the 22 patients demonstrated a response per RECIST 1.1. One patient who was treated at the 2.40 dose level demonstrated a CR and 3 patients in the overall cohort experienced a partial response– 1 each at the 0.6 mg/m2, 0.24 mg/m2, and 2.4 mg/m2 dose levels. Ten patients had stable disease (SD), 1 experienced disease progression, and 1 patients was not evaluable for response. Three patients in the local effect cohort achieved a CR and 3 had SD.

In terms of safety, most adverse effects (AEs) were mild to moderate (96%); AEs were reported at grade 1 (n = 135), grade 2 (n = 81), grade 3 (n = 6), and grade 4 (n = 2) severities. There was also 1 dose-limiting toxicity, 2 serious AEs, 160 treatment-emergent AEs, and no deaths. The MTD was not reached, but dose escalation stopped at 3.6 mg/m2, which was determined by investigators to have provided an appropriate balance between safety and potential efficacy.

In November 2023, during the CTOS Annual Meeting, a trial in progress abstract was presented regarding the QB46C-H07 trial. During the presentation, investigators highlighted that at the time of submission, 1 patient with regionally recurrent myxofibrosarcoma had been treated with tigilanol tiglate and another patient was in screening. The study is currently open to enrollment and is estimated to be completed in March 2025.2,3


  1. QBiotics drug tigilanol tiglate awarded Orphan Drug Designation for patients with soft tissue sarcoma. News release. QBiotics Group Limited. February 16, 2024. Accessed February 16, 2024. https://qbiotics.com/investors/announcements/26-news/377-qbiotics-drug-tigilanol-tiglate-awarded-orphan-drug-designation-for-patients-with-soft-tissue-sarcoma
  2. A Clinical Study to Investigate the Efficacy of Intratumoral Tigilanol Tiglate in Soft Tissue Sarcoma. ClinicalTrials.gov. Updated May 31, 2023. Accessed February 16, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05755113?term=NCT05755113&draw=2&rank=1
  3. Bartlett EK, Li D, Agaram N, et al. A pilot phase II study to evaluate the small molecule tigilanol tiglate in patients with advanced soft tissue sarcoma: clinical trial in progress. Presented at: 2023 CTOS Annual Meeting; November 1-4, 2023; Dublin, Ireland. Abstract P555.
  4. Panizza BJ, de Souza P, Cooper A, Roohullah A, Karapetis CS, Lickliter JD. Phase I dose-escalation study to determine the safety, tolerability, preliminary efficacy and pharmacokinetics of an intratumoral injection of tigilanol tiglate (EBC-46). EBioMedicine. 2019;50:433-441. doi:10.1016/j.ebiom.2019.11.037

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