1075P - Phase I study of CC-90010 in patients with advanced solid tumours and relapsed/refractory non-Hodgkin lymphoma (R/R NHL)

Bromodomain and extra-terminal (BET) proteins are epigenetic readers that regulate the expression of genes involved in cell growth and oncogenesis. CC-90010 is a potent, reversible oral BET inhibitor that reduces tumor growth in xenograft models. CC-90010-ST-001 (NCT03220347; 2015-004371-79) is a phase I, first-in-human study of CC-90010 in patients (pts) with advanced solid tumors and R/R NHL. Four dosing schedules and 11 dose levels were evaluated (Table). Primary objectives were to determine maximum-tolerated dose, safety, and/or recommended phase II dose (RP2D). A Bayesian logistic regression model guided the dose escalation. Secondary objectives were to identify early activity signals, pharmacokinetics, and pharmacodynamics (PD). As of 4 Mar 2019, 69 pts were enrolled, 67 with solid tumors, including 10 with glioblastoma and 2 with R/R NHL. Median age was 57 y (range, 21–80), 38 (55%) were men, and median number of prior systemic anticancer regimens was 3 (range, 1–9). Two RP2Ds were identified (dose cohorts 3A and 4B); 4B was selected for expansion. Dose-limiting toxicities (n=6) occurred in dose cohorts 3A, 3C, and 4B. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 21 pts (30%), most commonly (>2 pts) thrombocytopenia (16%), asthenia/fatigue (4%), and anemia (4%). Seven pts died, all from progressive disease.Eleven pts remained on treatment >6mo with clinical benefit. Two pts (endometrial carcinoma and astrocytoma) had a partial response, and 6 had prolonged stable disease ≥9mo. Plasma exposures and PD marker regulation increased with each dose level; terminal half-life was ∼73h. Most TRAEs were mild or moderate in severity and manageable with dose modifications. CC-90010 had a long terminal half-life that enabled less frequent dosing and promising anticancer activity. Dose escalation is complete, and expansion in select advanced malignancies is ongoing.Table: 1075PTable: 1075PDose Level:1 (n=7)2 (n=7)3A (n=4)3B (n=6)3C (n=6)4A (n=7)4B (n=7)4C (n=7)5A (n=6)5B (n=6)5C (n=6)Dose, mg1515253015404525305535Schedule, days on/off3/43/113/114/242/53/114/242/53/114/242/5 NCT03220347; 2015-004371-79. Tisheeka Graham-Steed, PhD BioConnections, LLC. Celgene Corporation. Celgene Corporation. V. Moreno: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Regeneron; Speaker Bureau / Expert testimony: Bayer/Loxo. I. Brana: Research gr