Phase I study of CC-90010, a reversible, oral BET inhibitor in patients with advanced solid tumors and relapsed/refractory non-Hodgkin lymphoma.

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Bromodomain and extra-terminal (BET) proteins are epigenetic readers that regulate expression of genes involved in oncogenesis. CC-90010 is a novel, oral, reversible, small-molecule BET inhibitor.CC-90010-ST-001 (NCT03220347; 2015-004371-79) is a phase I dose-escalation and expansion study of CC-90010 in patients with advanced or unresectable solid tumors and relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). We report results from the dose escalation phase, which explored 11 dose levels and 4 dosing schedules, 2 weekly [2 days on/5 days off; 3 days on/4 days off], 1 biweekly [3 days on/11 days off], and 1 monthly [4 days on/24 days off]). Primary objectives were to determine the safety, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and schedule. Secondary objectives were to evaluate signals of early anti-tumor activity, pharmacokinetics, and pharmacodynamics.This study enrolled 69 patients, 67 with solid tumors and 2 with diffuse large B-cell lymphoma (DLBCL). Median age was 57 years (range, 21-80) and median number of prior regimens was 4 (range, 1-9). Treatment-related adverse events (TRAEs) were mostly mild and manageable; grade 3/4 TRAEs reported in >2 patients were thrombocytopenia (13%), anemia, and fatigue (4% each). Six patients had dose-limiting toxicities. MTDs were 15 mg (2 days on/5 days off), 30 mg (3 days on/11 days off), and 45 mg (4 days on/24 days off). The RP2D and schedule selected for expansion was 45 mg (4 days on/24 days off). As of October 8, 2019, 1 patient with grade 2 astrocytoma achieved a complete response, 1 patient with endometrial carcinoma had a partial response, and 6 patients had prolonged stable disease ≥11 months.CC-90010 is well-tolerated, with single-agent activity in patients with heavily pretreated, advanced solid tumors.

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