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306 A Multicenter Phase2 Trial of Linperlisib in Relapsed or Refractory Peripheral T/NK Cell Lymphomas

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Hodgkin Lymphomas and T/NK Cell Lymphomas: Clinical and Epidemiological: Advances in Treating T Cell Lymphomas
Hematology Disease Topics & Pathways:
adult, Lymphomas, Non-Biological therapies, T Cell lymphoma, drug development, Diseases, Therapies, Lymphoid Malignancies, Pharmacology, Study Population, Human
Saturday, December 9, 2023: 5:15 PM

Yuqin Song, MD1, Zengjun Li2*, Huijing Wu, MD3*, Jie Jin, MD4, Hui Zhou5, Keshu Zhou, MD6*, Liling Zhang7*, Zhigang Peng, MD8*, Zhiye Zhang, MD9*, Hong Cen, MD10*, Youchao Jia, MD11*, Yuerong Shuang12*, Zhiming Li13*, Haiyan Yang14*, Liqun Zou, MD, PhD15*, Zhifeng Li16*, Zhihui Zhang, MD17*, Junmin Li18*, Junning Cao19, Lugui Qiu20, Shaojie Wu21*, Tiejun Gong22*, Xiaohong Xu, MD23*, Zhen Wang, MD24* and Jun Zhu, PhD25

1Department of Lymphoma, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, BEIJING, China
2Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
3Hubei Cancer Hospital, Wuhan, China
4Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
5Hunan Cancer Hospital, Changsha, China
6Department of Hematology, Cancer Hospital Affiliated to Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
7Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
8Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, NANING, CHN
9Department of Oncology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
10Department of Medical Oncology, Guangxi Medical University Affiliated Tumor Hospital, Nanning, CHN
11Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, China
12Jiangxi Cancer Hospital, Nanchang, China
13Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
14Zhejiang Cancer Hospital, Hangzhou, China
15Department of Medical Oncology, West China School of Medicine, West China Hospital of Sichuan University, Chengdu, China
16Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, Xiamen, China
17Sichuan Cancer Hospital and Institute, Chengdu, China
18Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
19Department of Lymphoma, Fudan University Shanghai Cancer Center, Shanghai, China
20State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology& Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
21Department of Hematology, Zhujiang Hospital of Southern Medical University, Guangzhou, China
22Institute of Hematology and Oncology, Harbin First Hospital, Harbin, CHN
23Department of Hematology and Lymphoma, Cancer Hospital affiliated to Nantong University, Nantong, China
24Linyi Cancer Hospital, Linyi, China
25Department of Lymphoma, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, Beijing, China


Peripheral T/NK cell lymphomas (PTCLs) are a group of aggressive heterogeneous non-Hodgkin’s lymphomas where in relapsed or refractory (r/r) disease, the approved standard therapies are limited with a median progression free survival (mPFS) of only 3-4 months. PI3Kdelta inhibitors have demonstrated clinical activities in T-cell and B-cell lymphomas, owing to the multiple cellular activities in the T, B, and myeloid cell tumor microenvironment. However, application of these agents has been hampered by poor tolerabilities, particularly with toxicities such as diarrhea/colitis, hepatotoxicity, pneumonitis, hyperglycemia, and rash. As a new PI3Kdelta-selective oral agent, linperlisib was shown to be efficacious and indicated a favorable safety profile in phase 1 and 2 clinical trials in r/r Follicular Lymphoma (FL) and PTCL. Linperlisib received marketing approval in China in 2022 for r/r FL patients (pts) with 2 prior systemic therapies. Here we report the efficacy and safety findings for linperlisib in a pivotal phase 2 trial in r/r PTCL.


Ninety-eight pts were enrolled in the open-label phase 2 registration trial (CTR20210333) from May 2021 to October 2022 at 25 sites in China. The trial had a representation of different PTCL subtypes: AITL (48 pts), PTCL-NOS (24 pts), NKT (8 pts), ALCL (2 pts), MEITL (2 pts), Other (4 pts), and 10pt did not qualify as PTCL confirmed by independent pathology review, yielding a Full Analysis Set (FAS) of 88 pts for efficacy evaluation. Linperlisib was orally dosed at 80 mg QD (RP2D) continuously until disease progression, intolerable toxicity, or study withdrawal. Tumor assessments performed every 2 treatment cycles (28-day cycle) were evaluated with Lugano 2014 criteria by an Independent Review Committee. Safety was evaluated according to CTCAE v5.0.


In this phase 2 study, the median age was 57 years, ECOG 0-1 (100%). Most patients were diagnosed with Lugano 2014 Stage III (29 pts, 33%), or IV (49pts, 56%) diseases, and were refractory or relapsed to a median of 2 prior systemic therapies. Sixty-four pts (73%) had refractory diseases, 59 pts (67%) had relapsed diseases, and 35 pts (40%) were with both r/r.

Treatment related adverse events (TRAE) were observed in 94 pts (95.9%) , with the most common TRAEs (≥10%) being neutropenia (59%), leukopenia (47%), thrombocytopenia (32%), anaemia (24%), elevated alanine aminotransferase (23%), elevated aspartate aminotransferase (20%), pneumonia (20%), lymphocytopenia (17%), hypertriglyceridemia (15%), fever (15%), diarrhea (14%), elevated lipase (13%), hyperuricemia (13%), rash (13%), hypercholesterolemia (12%), hyponatremia (11%), elevated lactate dehydrogenase (10%), elevated creatinine (10%). AEs of ≥Grade 3 (≥5%) were neutropenia (32%), pneumonia (14%), leukopenia (10%), anaemia (6%), thrombocytopenia (5%), upper respiratory tract infection (5%) and lymphocytopenia (5%). The most frequent Serious Adverse Event (drug-related) was pneumonia (11%). Twenty-two pts (22.4%) had dose reductions, and 9 pts (9.2%) discontinued from the study due to AEs. The safety profile was consistent with all previously reported in linperlisib clinical studies.

Among the 88 FAS pts, the objective response rate (ORR) was 48%, including 30% (26 pts) complete response, 18% (16 pts) partial response, and 20% (18 pts) stable disease. The disease control rate was 68%. Responses were demonstrated in all subtypes, including AITL, PTCL-NOS, NKT, and others. As of April 24, 2023, the median duration of response had not been reached (95%CI: 7.8, NR), and mPFS was 5.5 months (95%CI: 3.5, 15.6). All pts had ≥6 months of follow-up as of the safety and efficacy analysis data cut off (April 24, 2023); median follow-up was 13.9 months. The 6-month OS rate was 75% (95% CI: 64.51%, 82.74%), the median OS was 14.2 months (95%CI: 7.9, NR), 16 pts continued to receive linperlisib treatment.


Linperlisib, as a new PI3Kdelta-selective oral agent, showed a well-tolerated safety profile with low levels of severe gastrointestinal and liver toxicities seen with other PI3K agents. In r/r PTCL, linperlisib had promising durable efficacies, with 48% ORR (30% CR) and a median duration of response that was not reached. As in previous lymphoma studies with linperlisib, a high proportion of responses were CRs, and responses were observed across almost all PTCL subtypes. A phase 2 r/r PTCL and CTCL trial in the US/EU is ongoing.

Disclosures: No relevant conflicts of interest to declare.

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