SAN DIEGO—TRACON Pharmaceuticals, a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration and fibrotic diseases, in late January announced that positive clinical data from its ongoing Phase 1b/2 study of TRC105 and Nexavar (sorafenib) in patients with advanced hepatocellular carcinoma (HCC) were presented in a poster presentation at the ASCO 2019 Gastrointestinal Cancers Symposium in San Francisco.
Data from the ongoing open-label, non-randomized study were presented by Dr. Kanwal Raghav from the University of Texas MD Anderson Cancer Center. Key results included:
- Confirmed partial response by RECIST 1.1 occurred in 3 of 15 (20 percent) evaluable patients and a reduction of 50 percent or greater in alpha fetoprotein (AFP) concentration occurred in 8 of 16 (50 percent) evaluable patients. Reduction in AFP, a tumor marker expressed in patients with HCC, in early treatment may help predict a favorable response to treatment.
- Adverse events expected of each drug did not increase in frequency or severity when TRC105 and sorafenib were administered concurrently.
- TRC105 trough concentrations were lower in HCC patients compared with prior TRC105 studies in other tumor types, and weekly dosing at the recommended Phase 2 dose of TRC105 of 10 mg/kg, rather than every other week dosing, was required to exceed target concentrations consistently. This may reflect increased target mediated clearance in HCC patients via fibrotic/cirrhotic liver disease.
- Anti-drug antibody (ADA) was observed more frequently in patients with HCC (76 percent) compared with prior studies of TRC105 in other tumor types (e.g., in RCC, sarcoma, and lung cancer patients where ADA has been approximately 5 percent) and may have influenced pharmacokinetics in individual patients.
“We continue to be encouraged by the safety and activity of TRC105 in combination with Nexavar in patients with liver cancer,” said Dr. Charles Theuer, president and CEO of TRACON. “Importantly, the response rate from the current trial is superior to historic response rates reported from multiple trials of Nexavar as a single agent. We expect to complete enrollment of the current multicenter study by the end of this year, at which time we expect to correlate response with the soluble baseline biomarkers that are being collected as part of the study.”