A phase I study of TGF-β inhibitor, vactosertib in combination with imatinib in patients with advanced desmoid tumor (aggressive fibromatosis).

Abstract

11557 Background: Desmoid tumor (aggressive fibromatosis) is fibroproliferative neoplasm arising from deep connective tissues. TCGA pan-cancer analysis revealed high expression TGF-β responsive signature in desmoid tumor. This phase I study assessed the safety, tolerability, and pharmacokinetics of the TGF-β inhibitor, vactosertib in combination with imatinib for desmoid tumor. Methods: Patients with advanced desmoid tumors not treatable by surgery or radiotherapy were eligible. The primary objective is to assess the safety and recommended phase 2 dose (RP2D) of vactosertib given 5 days on and 2 days off in combination with imatinib (400 mg QD). Two dose levels of vactosertib were tested; cohort -1 (100 mg BID) and cohort 1(200 mg BID). Secondary objectives include pharmacokinetics, anti-tumor activity by response rate (RECIST v1.1), and biomarker analysis. Results: Seven patients (cohort -1, n = 4; cohort 1, n = 3) were enrolled and finished the safety evaluation. The most frequently reported treatment related adverse events were myalgia (57.1%), fatigue (42.8%), diarrhea (42.8%), anemia (28.5%) and stomatitis (28.5%) with mostly grade 1. No dose limiting toxicity was observed. Tumor response included 2 (28.5%) partial response (PR) and 2 stable disease (SD) in the cohort -1, and 3 SD in the cohort 1. The time to response were 5.5 and 8.2 months and all 7 cases are ongoing. Updated safety, pharmacokinetics, efficacy and biomarker data will be presented at the meeting. Conclusions: The combination of vactosertib plus imatinib was well tolerated and showed promising activity in desmoid tumor. RP2D of vactosertib was defined as 200 mg BID. Further efficacy will be explored in the phase 2 part of the study. Clinical trial information: NCT03802084 .