Lysine-Specific Demethylase-1 Inhibitor CC-90011 in Patients With Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma

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 and its expression in cancer stem cells is associated with chemoresistance. CC-90011 is a potent, selective, and reversible oral LSD1 inhibitor. We examined CC-90011 in advanced solid tumors and relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). EXPERIMENTAL DESIGN: CC-90011-ST-001 (NCT02875223; 2015-005243-13) is a phase I, multicenter, first-in-human dose escalation study. Nine dose levels of CC-90011 (1.25 mg to 120 mg) given once/week (QW) were explored. Primary objectives were to determine safety, maximum tolerated dose (MTD), and/or recommended phase 2 dose (RP2D). Secondary objectives were to evaluate preliminary efficacy and pharmacokinetics. RESULTS: Fifty patients were enrolled, 49 with solid tumors (27 neuroendocrine tumors/carcinomas [NETs/NECs]) and 1 with R/R NHL. Median age was 61 years (range, 22-75). Patients received a median of 3 (range, 1-9) prior anticancer regimens. The RP2D was 60 mg QW; the nontolerated dose (NTD) and MTD were 120 mg QW and 80 mg QW, respectively. Grade 3/4 treatment-related toxicities were thrombocytopenia (20.0%; an on-target effect unassociated with clinically significant bleeding), neutropenia (8.0%; in the context of thrombocytopenia at the highest doses), and fatigue (2.0%). The patient with R/R NHL had a complete response, currently ongoing in cycle 27; 8 patients with NETs/NECs had stable disease ≥6 months, including bronchial NETs, kidney tumor, and paraganglioma. CONCLUSIONS: CC-90011 is well-tolerated, with the RP2D established as 60 mg QW. The MTD and NTD were determined to be 80 mg QW and 120 mg QW, respectively. Further evaluation of CC-90011 is warranted.