This phase 1a/1b study evaluated safety, tolerability, and preliminary efficacy of ACY-241 monotherapy in combination with pomalidomide (Pom) and dexamethasone (Dex); results were presented at the ASH 2016 Annual Meeting. Patients were treated with a single cycle of ACY-241 monotherapy followed by ACY-241 in combination with Pom (4 mg) and low-dose Dex in patients with relapsed or relapsed/refractory multiple myeloma. Cohorts of 3 patients received ACY-241 once daily as monotherapy (180, 360, and 480 mg) on days 1 to 21 of a 28-day cycle. Patients tolerating this initial cycle continued to cycle 2 of combination therapy with ACY-241/Pom/Dex.
A total of 63 patients have enrolled in the study, with a median age of 62 years. Median number of prior regimens was 2 (1-10). Seventy-six percent of patients were refractory to Len and 40% to both bortezomib and Len. Toxicities were primarily grade 1 or 2. In patients who received a dose of 360 mg of ACY-241 in combination with Pom and Dex, grade 3/4 toxicities included neutropenia (14 patients, 35%), anemia (10 patients, 25%), thrombocytopenia (6 patients, 15%), back pain (4 patients, 10%), and leukopenia (4 patients, 10%). Pharmacokinetic results showed a dose-linear increase in exposure with increasing dose, no accumulation, and no drug–drug interaction with Pom and Dex. Efficacy data for combination treatment (N = 56 evaluable patients, all refractory to last treatment regimen) showed the following: 7 very good partial responses, 19 partial responses, 7 minimal responses, 18 with stable disease, and 5 with progressive disease. Median duration of response was 9.2 months, and median progression-free survival was 6.5 months.
Investigators concluded that ACY-241 was well-tolerated in monotherapy at a dose of 480 mg daily and in combination with Pom/Dex at a dose of 360 mg daily. Initial response data are also promising; researchers anticipate that efficacy may compare favorably to the combination of Pom and Dex, but further study is required.
Niesvizky R, et al. ASH 2016. Abstract 3307.