DCC-3014 Well-Tolerated, Active in Patients With Diffuse-Type TGCT

Tokyo, Japan—Findings from a phase 1 study demonstrate that DCC-3014 is active and generally well-tolerated in patients with diffuse-type tenosynovial giant cell tumor (TGCT), according to data that was presented at the Connective Tissue Oncology Society 2019 Annual Meeting.

“DCC-3014 is an orally administered, potent, and selective inhibitor of CSF1 receptor that was engineered to bind as a switch control inhibitor of CSF1 receptor and inhibit kinase activity,” explained Breelyn Wilky, MD, Division of Medical Oncology, University of Colorado, Denver, and colleagues, who developed an ongoing phase 1 clinical trial assessing the safety, preliminary anti-tumor activity, pharmacokinetics (PK), and pharmacodynamics (PD) of DCC-3014 in patients with advanced solid tumors, including diffuse-type TGCT.

The multi-center, open-label, single-arm study by Dr Wilky et al consisted of 2 parts,  a dose-escalation phase and a dose-expansion phase. The purpose of the dose-escalation phase was to determine the recommended dose of DCC-3014 for phase 2 study as well as the maximum-tolerated dose (MTD). The dose-expansion phase was carried out to assess the safety, tolerability, preliminary anti-tumor activity, PK, and PD of the drug.

As of September 2019, a total of 39 patients were enrolled in the study, including 3 patients with diffuse-type TGCT. These patients were given a loading dose of DCC-3014 30 mg daily for 5 days followed by 30 mg administered twice weekly.

Thus far, DCC-3014 has demonstrated rapid, preliminary anti-tumor activity in these 3 patients by administration of cycle 3. Of note, 1 patient had a confirmed partial response at cycle 3 that was maintained for 9 months and is still ongoing.

According to the investigators, all 3 patients with diffuse-type TGCT had symptomatic improvements in mobility and reduced pain.

“Exposure to DCC-3014 was consistent between malignant solid tumor and diffuse-type TGCT patients and associated with an increase in plasma CSF1 and IL-34 in plasma, and a rapid, sustained reduction of CD16+ monocytes in peripheral blood,” Dr Wilky and colleagues said.

“Dose-escalation evaluation is ongoing to determine the recommended phase 2 dose….These results are encouraging and support further evaluation of DCC-3014 in diffuse-type TGCT,” they concluded.—Hina Porcelli

Wilky B, Taylor M, Bauer T, et al. Phase 1 study of DCC-3014 to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with malignant solid tumors and diffuse-type tenosynovial giant cell tumor. Presented at: the Connective Tissue Oncology Society 2019 Annual Meeting; November 13-16; Tokyo, Japan. Abstract 3241734.