528O CC-90011 in patients (Pts) with advanced solid tumours (STs) and relapsed/refractory non-Hodgkin lymphoma (R/R NHL): Updated results of a phase I study

Abstract

CC-90011 is an oral, potent, selective, reversible inhibitor of lysine-specific demethylase 1A. CC-90011 was well tolerated and had promising antitumor activity in pts with advanced unresectable STs and R/R NHL in the dose-escalation part of the CC-90011-ST-001 study. Here we present updated results from the cohort expansion part of the study. Pts in this phase I, dose-escalation (part A) and -expansion (part B), first-in-human study received CC-90011 once/wk (QW) in 28-d cycles. Primary endpoints were safety, maximum tolerated dose (MTD), and recommended phase II dose (RP2D). Secondary and exploratory endpoints included pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy. Sixty-six pts enrolled, 50 in part A (27 with neuroendocrine neoplasms [NENs] and 1 with R/R NHL) and 16 in part B (all with NENs). The RP2D was 60 mg QW. As of 17 Jan 2020, 4 pts (3 with NENs, 1 with R/R NHL) in part A and 2 pts in part B remained on treatment (tx). The primary reason for tx discontinuation was progressive disease (part A, n=38 [76%]; part B, n=12 [75%]). Thrombocytopenia was the most common tx-related adverse event (AE; 47%), and the only serious AE reported in >1 pt in either part of the study; this on-target toxicity was reversible and manageable. AEs led to discontinuation in 3 pts (6%), all in part A. Two pts in part A and 1 in part B died due to underlying disease; there were no deaths due to tx-related AEs. Clinical benefit rate (partial or complete response [CR] or stable disease [SD] ≥4 mo) was 20% (95% CI, 10.0-33.7) in part A and 44% (95% CI, 19.8-70.1) in part B. In part A, the R/R NHL pt achieved a CR (ongoing in cycle 32) and 5 pts with NENs had SD ≥9 cycles, including 2 with SD ≥21 cycles. In part B, 3 pts with NENs had SD ≥9 cycles. Exposure increased proportional to dose. Negligible accumulation of exposure occurred with repeat dosing and systemic exposures at the same dose were similar in parts A and B. Decreased levels of chromogranin A and peripheral blood PD biomarker, MMD, indicated CC-90011 target engagement. CC-90011 was well tolerated with favorable PK/PD profiles. Promising antitumor activity was observed in pts with NENs and R/R NHL.