Phase II study of chidamide (CS055), a new subtype-selective oral histone deacetylase inhibitor, in patients with relapsed or refractory peripheral T-cell lymphoma.

Abstract

8525 Background: Chidamide (CS055) is a new benzamide type of histone deacetylase (HDAC) inhibitor with subtype selective activity against HDAC1, 2, 3 and 10. Chidamide has shown well-tolerated and favorable PK profiles in patients (pts) with advanced solid tumors and lymphomas. This phase II study was to evaluate the efficacy and safety of chidamide in relapsed or refractory peripheral T-cell lymphoma (PTCL). Methods: 102 PTCL pts were enrolled. In the exploratory trial, pts were randomized to receive chidamide 30mg or 50mg twice per week for 2 weeks, followed by 1 week of rest. In the pivotal trial, chidamide was administered 30mg twice per week w/o drug-free holiday. The primary endpoint was overall response rate (ORR). Responses were assessed using IWC criteria. Results: In the exploratory trial, 19 pts were enrolled with 9 and 10 to the 30mg and 50mg arms, respectively. ORR was 11.1% (1 CR) in the 30mg arm and 40.0% (1 CR, 1 CRu, 2 PR) in the 50mg arm. One pt in the 50mg arm experienced drug-related grade 4 thrombocytopenia. In the pivotal trial, 83 pts were enrolled. Most pts were stage III (35.2%) or IV (45.9%). 23 pts (29.1%) had confirmed responses out of 79 evaluable pts in the pivotal trial (8 CR, 3 CRu, and 12 PR). Responses of 19 pts (24.1%) maintained for ≥12 weeks. ORR with 27.8% was obtained by the Independent Review Committee. 68 pts (81.9%) experienced at least 1 AE in the pivotal trial, with 52.9% of AEs ≤ grade 2. The most common AEs were thrombocytopenia (50.6%), leucocytopenia (39.8%), neutropenia(21.7%), and fatigue (9.6%). 1 pt had a grade 3 QTc prolongation. 7 pts (8.4%) experienced at least one SAE, in which a grade 4 thrombocytopenia was considered to be drug-related. 2 pts with responses (CR) have received chidamide for > 43 months w/o evidence of cumulative toxicity. Conclusions: Chidamide as an oral single agent had significant and durable activity in pts with relapsed or refractory PTCL. Toxicities with the therapy were generally tolerable and manageable. The overall differences in pathological subtypes of pts enrolled and clinical profiles between chidamide and the two existing drugs, pralatrexate and romidepsin, will be discussed. Clinical trial information: ChiCTR-TNC-10000811.