Phase I clinical tolerance study of chidamide(CS055) in patients with advanced cancer

Objective:Chidamide (CS055) is a new histone deacetylase (HDAC) inhibitor. This phase I study evaluated the safety and tolerability of chidamide in patients with advanced solid tumors and lymphomas.Methods:31 patients with refractory or relapsed advanced solid tumors (22) and lymphomas (9) were enrolled in this study.Escalating doses of 5,10,17.5,25,32.5 and 50 mg chidamide (each with 3 to 7 patients) were administered orally either twice or three times per week for 4 consecutive weeks every 6 weeks.Results:No dose limiting toxicities (DLTs) were identified in the twice per week cohorts (22 patients) up to 50 mg.G2 and G3 hematological toxicities (leukopenia/neutropenia and thrombocytopenia) were observed in the arm with 50 mg.DLTs were reported as G3 diarrhea or vomiting in 2 patients in the three times per week cohort at 50 mg.Common adverse events were G1/G2,fatigue,thrombocytopenia,anorexia,nausea/vomiting,leukopenia/neutropenia,and diarrhea.25 patients were evaluated for efficacy.4 patients with T-cell lymphomas (4/5 evaluable) and 1 patient with submandibular adenoid cystic carcinoma achieved partial response(PR),and 11 patients experienced stable disease(SD).Conclusions:Chidamide is well-tolerated in patients with advanced cancer in the tested regimens. Preliminary results showed a good response in lymphoma patients. We recommend further phase II study should be done in patients with malignant lymphoma firstly.The regimens of dose ≤50 mg twice a week or dose≤32.5 mg three times a week for 4 consecutive weeks with 2 weeks interval are recommended for phase II study.