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Clinical Activity of TGF-β Inhibitor Vactosertib in Combination with Imatinib in Desmoid Tumors: A Multicenter Phase
Jin-Hee Ahn1, Jeeyun Lee2, Changhee Park3
1Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
Purpose:
The study was to determine the activity and safety of the TGF-β inhibitor vactosertib in combination with imatinib in patients with desmoid tumors.
Patients And Methods:
In this investigator-initiated, open-label, multicenter, phase Ib/II trial, patients with desmoid tumors not amenable to locoregional therapies (surgery and/or radiotherapy) or with disease progression following at least one treatment were enrolled. Participants were administered 400 mg imatinib daily in combination with vactosertib (5 days on and 2 days off, twice a day) every 28 days. In phase Ib, the vactosertib dose was set at 100 mg (level -1) and 200 mg (level 1) to determine the recommended phase II dose (RP2D). Phase II assessed the efficacy, with the primary endpoint being progression-free rate (PFR) at 16 weeks.
Results:
No dose-limiting toxicities were observed during phase Ib; therefore RP2D was defined at doses of 400 mg imatinib daily in combination with 200 mg vactosertib. Of the 27 patients evaluated, 7 (25.9%) achieved a confirmed partial response and 19 (70.4%) were stable. The PFR at 16 weeks and 1 year were 96.3% and 81.0%, respectively. Most toxicities were mild to moderate myalgia (n = 10, 37%), anemia (n = 10, 37%), and nausea (n = 9, 33.3%). Common grade 3 to 4 toxicities included neutropenia (n = 6, 22.2%) and anemia (n = 5, 18.5%).
Conclusions:
The vactosertib and imatinib combination was well tolerated, with promising clinical activity in patients with progressive, locally advanced desmoid tumors. This is the first study investigating a novel target agent, a TGF-β inhibitor, in this rare and difficult-to-treat desmoid tumor.
Insights
The combination of vactosertib and imatinib showed promising activity and was well-tolerated in patients with desmoid tumors. This novel TGF-β inhibitor combination offers a new treatment option for this rare cancer.
Area of Science:
- Oncology
- Pharmacology
Background:
- Desmoid tumors are rare, locally aggressive neoplasms with limited treatment options.
- Transforming growth factor-beta (TGF-β) signaling is implicated in desmoid tumor pathogenesis.
Purpose of the Study:
- To evaluate the safety and efficacy of vactosertib, a TGF-β inhibitor, combined with imatinib in patients with desmoid tumors.
- To determine the recommended phase II dose (RP2D) for this combination therapy.
Main Methods:
- An investigator-initiated, open-label, multicenter, phase Ib/II trial.
- Patients received 400 mg imatinib daily with escalating doses of vactosertib (100 mg or 200 mg) in phase Ib to determine RP2D.
- Phase II assessed efficacy, with progression-free rate (PFR) at 16 weeks as the primary endpoint.
Main Results:
- The RP2D was established at 400 mg imatinib daily and 200 mg vactosertib (twice daily, 5 days on/2 days off).
- Of 27 patients, 96.3% achieved a 16-week PFR, with an 81.0% PFR at 1 year.
- Partial response was observed in 25.9% and stable disease in 70.4% of patients.
- Most common toxicities included myalgia, anemia, and nausea; grade 3-4 toxicities were neutropenia and anemia.
Conclusions:
- The combination of vactosertib and imatinib demonstrated promising clinical activity and was well-tolerated in patients with progressive desmoid tumors.
- This study represents the first investigation of a TGF-β inhibitor in combination with imatinib for desmoid tumors, offering a novel therapeutic strategy.
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