Phase 1 trial of the oral STAT3 inhibitor TTI-101 in patients with advanced solid tumors

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is essential for the survival of cancer cells. TTI-101 is a first-in-class, oral, selective small-molecule inhibitor of STAT3. A phase 1 trial at MD Anderson Cancer Center (Houston, TX) evaluated TTI-101 in patients with advanced solid tumors. Patients were treated with TTI-101 orally twice daily at 4 dose levels; dose level 3 (12.8 mg/kg/d) was chosen as recommended phase 2 dose. There were no dose-limiting toxicities or fatal treatment-related adverse events. Diarrhea (mostly grade 1 or 2) was the only TRAE observed in ≥ 30% of patients. Eight percent of patients had grade 3 TRAEs that resolved. Of the 41 patients who were evaluable for response, 5 (12%) had confirmed partial responses (cPRs) and 17 (41%) had stable disease. Three (18%) of 17 patients with hepatocellular carcinoma had a cPR (median time to treatment failure, 10.6 months). The authors conclude that TTI-101 was well-tolerated and had promising antitumor activity in patients with advanced solid tumors. A phase 2 study of TTI-101 in hepatocellular carcinoma is currently underway.