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Updated: Jun 28, 2026
A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing (Neo)adjuvant Therapies
Published on: July 28, 2020
Randomized, phase II study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 in patients with advanced
Laurence H Baker1, Eric K Rowinsky, David Mendelson
1University of Michigan Medical School, Ann Arbor, MI 48106, USA. bakerl@umich.edu
Purpose:
Sarcomas are among the most proangiogenic malignancies in preclinical models. Phase I study results for ABT-510, which inhibits angiogenesis via a novel thrombospondin-mimetic mechanism, suggested activity in soft tissue sarcoma (STS) patients. This phase II study further evaluated the safety and efficacy of ABT-510 in advanced STS patients.
Patients And Methods:
Patients with metastatic or unresectable STS were randomly assigned to treatment with one of two ABT-510 dose schedules (20 mg once a day [20 mg], n = 42; or 100 mg twice a day [200 mg], n = 46), which were self-administered subcutaneously in 28-day treatment periods. End points included progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and safety.
Results:
Median PFS for the 20-mg arm was 94 days, with 4- and 6-month PFS rate estimates of 42% and 24%, respectively. Median PFS for the 200-mg arm was 64 days, with 4- and 6-month PFS rate estimates of 41% and 32%, respectively. Although only one objective response was noted, stable disease was observed in 52% (20 mg) and 48% (200 mg) of patients. Median OS was 431 days (20 mg) and 295 days (200 mg). ABT-510 was well tolerated. Rare treatment-related grade 3 or 4 adverse events were one event each of hypotension, deep vein thrombosis, and hypophosphatemia. ABT-510 pharmacokinetics were dose proportional, time independent, and consistent with those in previous studies.
Conclusion:
ABT-510 had a favorable safety profile, and the rate of disease control and OS times were encouraging. However, with low ORR and lack of dose response, the study failed to yield compelling evidence of strong single-agent activity in STS.
Insights
This study evaluated ABT-510 for advanced soft tissue sarcoma (STS). While well-tolerated, ABT-510 showed limited efficacy, failing to demonstrate strong single-agent activity in STS patients.
Area of Science:
- Oncology
- Medical Research
- Pharmacology
Background:
- Sarcomas exhibit high proangiogenic potential in preclinical models.
- ABT-510, a thrombospondin-mimetic agent, targets angiogenesis.
- Phase I studies suggested potential activity of ABT-510 in soft tissue sarcoma (STS).
Purpose of the Study:
- To evaluate the safety and efficacy of ABT-510 in patients with advanced STS.
- To compare two different dosing schedules of ABT-510.
Main Methods:
- A phase II, randomized study of patients with metastatic or unresectable STS.
- Patients received ABT-510 subcutaneously at 20 mg once daily or 200 mg twice daily.
- Primary end points included progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and safety.
Main Results:
- Median PFS was 94 days (20 mg) and 64 days (200 mg).
- Stable disease was observed in 52% (20 mg) and 48% (200 mg) of patients; ORR was low.
- Median OS was 431 days (20 mg) and 295 days (200 mg); ABT-510 was well tolerated.
Conclusions:
- ABT-510 demonstrated a favorable safety profile in advanced STS patients.
- Encouraging disease control rates and overall survival times were observed.
- The study did not provide compelling evidence of strong single-agent activity due to low ORR and lack of dose response.
