Phase I/II study of linperlisib plus chidamide in relapsed or refractory cutaneous t-cell lymphoma: A prospective single-center study

Summary: Abstract Body: This study aimed to evaluate the safety and efficacy of the combination of linperlisib, a PI3K inhibitor, and chidamide, a histone deacetylase (HDAC) inhibitor, in patients with relapsed or refractory (R/R) cutaneous T-cell lymphoma (CTCL). A prospective, single-center, phase I/II trial was conducted using a “3+3” dose-escalation design. Phase I assessed safety, maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) to determine the recommended phase II dose (RP2D). Phase II primarily evaluated objective response rate (ORR). Linperlisib was administered once daily at escalating doses (40 mg, 60 mg, 80 mg), and chidamide was fixed at 20 mg twice weekly. Between May 1, 2023, and December 31, 2024, 21 patients (12 males, 9 females; median age 43 years) with advanced CTCL, including 18 with mycosis fungoides (MF) and 3 with Sézary syndrome (SS), were enrolled. The median number of prior treatments was 3, and all patients had an ECOG performance status of 0-2. The RP2D for linperlisib was 80 mg, as determined from phase I, with no DLTs observed in the first 9 patients. The most common treatment-related adverse events were nausea (38.1%), pruritus (33.3%), and rash (28.6%), mainly grade 1-2. Grade 3 adverse events included rash and hematologic toxicities (9.5% each). No grade 4 events were reported. In terms of efficacy, the ORR in all patients was 57.1% (12/21): 61.1% (11/18) in MF, 33.3% (1/3) in SS, respectively, with a disease control rate of 85.7% (18/21). 1 patient achieved complete response, and 11 achieved partial response. The median time to response was two months. In conclusion, the combination of linperlisib and chidamide demonstrated a manageable safety profile and promising efficacy in patients with R/R CTCL. This combination may offer a new therapeutic option for advanced CTCL. This trial was registered at www.clinicaltrials.gov as #NCT06037239. Zhiyu Pang¹, Yupeng Wang², Ziqian Wang², Zhuofan Xu², Zhaorui Liu¹, Shan Zhang¹, Chong Wei², Hongyun Chen², Jie Liu¹, Wei Zhang² 1. Department of Dermatology, Peking Union Medical College Hospital, Beijing, Beijing, China. 2. Department of Hematology, Peking Union Medical College Hospital, Beijing, Beijing, China. Clinical Research: Interventional Research