Date: 2015-06-16
Type of information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the 20th Congress of the European Hematology Association, in Vienna, Austria
Company: Acetylon Pharmaceuticals (USA - MA)
Product: ricolinostat (ACY-1215) in combination with Pomalyst® (pomalidomide) and dexamethasone
Action
mechanism: histone deacetylase inhibitor/HDAC inhibitor. Ricolinostat is a selective inhibitor of histone deacetylase (HDAC) 6.
Disease: relapsed and refractory multiple myeloma
Therapeutic area: Cancer - Oncology
Country: Canada, Italy, USA
Trial
details: The Phase 1b/2 clinical trial is a multi-center, open-label study designed to assess the safety, tolerability and efficacy of ricolinostat in combination with Pomalyst® and low-dose dexamethasone. The primary endpoint is overall response rate. (NCT01997840 )
Latest
news: * On June 16, 2015, Acetylon Pharmaceuticals announced that the Company presented positive preliminary data from its Phase 1b/2 trial of ricolinostat in combination with Pomalyst® (pomalidomide) and dexamethasone in patients with relapsed-and-refractory multiple myeloma at the 20th Congress of the European Hematology Association, which took place June 11-14, 2015, in Vienna, Austria. Initial data from the evaluation of 28 of the planned 66 patients in the Phase 2 portion of the study reported an overall response rate of 29% at an early median follow-up of 12 weeks, which compares favorably to the historical control of 16.6% at 18.1 weeks with Pomalyst and dexamethasone alone in a similar patient population. Clinical benefit, defined as minimal response or greater, was 50%, and 68% of patients achieved stable disease or better. In the overall study (Phase 1 and Phase 2, n=39), ricolinostat was well-tolerated in combination with Pomalyst. The most common treatment-emergent adverse events were fatigue (41%), diarrhea (38%), and neutropenia (36%), the majority of which were low grade. Grade 3 and 4 adverse events, apart from neutropenia (26%), were uncommon (?8%). Ricolinostat is an oral selective HDAC6 inhibitor in multiple clinical studies for the potential treatment of multiple myeloma and lymphoma. The Phase 1b/2 clinical trial is a multi-center, open-label study designed to assess the safety, tolerability and efficacy of ricolinostat in combination with Pomalyst® and low-dose dexamethasone. The primary endpoint is overall response rate. The Phase 1b portion was a 3+3 design in which ricolinostat (160 mg) was given QD (once daily) or BID (twice daily) combined with Pomalyst (4 mg) for 21 days of a 28-day cycle with dexamethasone (40 mg) on days 1, 8, 15 and 22. 7 patients were treated in the Phase 1b portion, with 3 at 160 mg QD and 4 at 160 mg BID. In the ongoing Phase 2 portion, up to 66 patients will be enrolled – of those patients, 32 had been enrolled as of April 27, 2015, of which 28 were evaluable for response. Ricolinostat is being administered orally as 160mg QD for 21 days of a 28-day cycle. Major highlights from the presentation include: The optimal dose and schedule for ricolinostat in combination with Pomalyst and dexamethasone was determined to be 160mg QD on days 1-21 of a 28-day cycle. Patients at this dose experienced no dose-limiting toxicities. At 160mg BID, some clinically-relevant grade 2 diarrhea was observed. Co-administration of Pomalyst® and ricolinostat did not alter either agent’s pharmacokinetic profile.
57% (16) of the Phase 2 evaluable patients remained on study after a median of 3 months on therapy, while 43% of patients discontinued treatment for reasons of progressive disease (6), a non-fatal adverse event (3), patient decision (2) and investigator decision (1).
The combination of ricolinostat, Pomalyst® and dexamethasone was generally well-tolerated. Serious adverse events considered possibly related to ricolinostat were bronchitis, chronic cardiac failure, pneumonia and renal failure, each reported for 1 patient. A single grade 4 adverse event, neutropenia, was reported to be possibly related to ricolinostat. Grade 3 related adverse events reported in 2 or more patients included diarrhea (3) and neutropenia (4).
