Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma

Purpose: Lysine-specific demethylase 1 (LSD1) is implicated in multiple tumor types, which is expression in cancer stem cells is associated with chemoresistance. CC-90011 can be a potent, selective, and reversible dental LSD1 inhibitor. We examined CC-90011 in advanced solid tumors and relapsed/refractory (R/R) non-Hodgkin lymphoma (Nhl).

Patients and methods: CC-90011-ST-001 (NCT02875223 2015-005243-13) can be a phase I, multicenter, first-in-human dose-escalation study. Nine dose levels of CC-90011 (1.25-120 mg) given once weekly were explored. Primary objectives would determine safety, maximum tolerated dose (MTD), and/or recommended phase II dose (RP2D). Secondary objectives would evaluate preliminary effectiveness and pharmacokinetics.

Results: Fifty patients were enrolled, 49 with solid tumors (27 neuroendocrine tumors/carcinomas) and 1 with R/R Nhl. Median age was 61 years (range, 22-75). Patients received typically three (range, 1-9) prior anticancer regimens. The RP2D was 60 mg once weekly the nontolerated dose (NTD) and MTD were 120 mg once weekly and 80 mg once weekly, correspondingly. Grade 3/4 treatment-related toxicities were thrombocytopenia (20% an on-target effect unassociated with clinically significant bleeding), neutropenia (8% poor thrombocytopenia within the finest doses), and fatigue (2%). The person with R/R Nhl stood a complete response, presently ongoing in cycle 34, and eight patients with neuroendocrine tumors/carcinomas had stable disease =6 several days, including bronchial neuroendocrine tumors, kidney tumor, and paraganglioma.

Conclusions: CC-90011 is well tolerated, while using RP2D established as 60 mg once CC-90011 weekly. The MTD and NTD would be 80 mg once weekly and 120 mg once weekly, correspondingly. Further take a look at CC-90011 is warranted.