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3075 Selective PI3Kδ Inhibitor Parsaclisib Combined with HDAC Inhibitor Chidamide in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma: Preliminary Results of a Phase Ib/Ⅱ Study

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Lymphomas, Clinical Research, Combination therapy, T Cell lymphoma, Diseases, Therapies, Lymphoid Malignancies, Adverse Events
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Zheng Yan1*, Shuna Yao2*, Shuang Zhao2*, Haiying Wang3*, Junfeng Chu3*, Yuanlin Xu2*, Jiuyang Zhang, MD3*, Lina Zhang, MD4*, Quande Lin, PhD5*, Lijie Liang6*, Ping Wang6*, Wenyong Li7*, Xiaolu Teng7*, Zhihua Yao, PhD2* and Yanyan Liu2*

1Department of Internal Medicine Affiliated Cancer Hospital of Zhengzhou Universi, Zhengzhou, China
2Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
3Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, CHN
4Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China., Zhengzhou, Henan, CHN
5Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
6Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
7Jiaozuo People's Hospital, Jiaozuo, China

Background: Peripheral T-cell lymphoma (PTCL) is a highly heterogenous non-Hodgkin lymphoma with poor survival. Pts with relapsed/refractory PTCL (r/r PTCL) have extremely poor prognosis and limited treatment options. Conventional salvage treatments have a median progression-free survival (PFS) of only 3-4 months. Parsaclisib, a potent, highly-selective, next-generation PI3Kδ inhibitor has shown encouraging efficacy and favorable safety profile in B-cell malignancies. We developed a phase Ib/II study to evaluate the safety and efficacy of parsaclisib with HDAC inhibitor (HDACi) chidamide in r/r PTCL (NCT05083208). Here, we report the preliminary results of this study.

Method: Eligible pts were ≤ 75 years old adults with histologically confirmed PTCL who received ≥ prior line of systemic therapy. Phase Ib dose-escalation study determined the maximum tolerated dose (MTD) of parsaclisib with chidamide using a 3 + 3 design. Parsaclisib was administered once daily at 3 dose levels (dose-level (DL) 1: 10 mg; DL2: 15 mg; DL3: 20mg) in the first 8 weeks followed by 2.5 mg QD in the subsequent treatment. Chidamide was administered at a fixed dose of 20 mg twice a week throughout the study. Once the MTD was established, pts were enrolled into phase 2 study to further characterize safety and efficacy. MTD of parsaclisib and objective response rate (ORR) were the primary endpoints; complete response rate (CRR), PFS, overall survival (OS) and tolerability were secondary endpoints. Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV) infection in the first 8 weeks were required.

Results: From March 2022 to July 27, 2023 (date cut-off), 11 pts were recruited with a median age of 52 (39-74) years old. The median number of prior systemic therapies was 2 (1-5). Of 6 pts treated at DL1, 1 had dose-limiting toxicity (DLT) (grade 3 elevation of ALT/AST). No DLT was observed in 3 pts at DL2 and 2 at DL3. The DLT was resolved subsequently but the patient died from lymphoma progression. Treatment-emergent adverse events (TEAEs) were observed in all pts. The TEAEs were mainly hematologic toxicities and gastrointestinal reactions, most of which were grade 1/2. Grade 3/4 TEAEs were neutropenia (n=4), leukopenia (n=1), elevation of ALT/AST (n=1), and diarrhea (n=1) (Table 1). TEAE led to dose interruption in one patient. In 9 pts evaluable for responses (1 withdrew from this study and 1 was unevaluable), 5 (55.6%) pts achieved complete response (CR) and one (11.1%) partial response at the first efficacy assessment. In 7 pts previously exposed to chidamide, 4 pts achieved CR and 2 of them had a PFS > 16 months (Table 2 and Figure 1).

Conclusion: Preliminary data demonstrated that selective PI3Kδ Inhibitor parsaclisib with HDACi chidamide was tolerable and produced promising responses in r/r PTCL, including patients previously exposed to chidamide. This trial is currently ongoing.

Disclosures: No relevant conflicts of interest to declare.

OffLabel Disclosure: Parsaclisib is a PI3Kδ Inhibitor. It has not been approved for the treatment of T-cell lymphoma.

*signifies non-member of ASH