[Translation] A multicenter phase II clinical study on the efficacy and safety of SHC014748M capsule in patients with relapsed or refractory peripheral T-cell lymphoma

主要目的：在剂量扩展阶段（Part A），初步评估SHC014748M胶囊在复发或难治的外周T细胞淋巴瘤患者中的有效性；在扩大样本量的有效性评估阶段（Part B），基于客观缓解率（ORR）评价SHC014748M胶囊在复发或难治的外周T细胞淋巴瘤患者中的有效性。次要目的：评价SHC014748M胶囊在复发或难治的外周T细胞巴瘤患者中的安全性。

[Translation]

The primary objective is to preliminarily evaluate the efficacy of SHC014748M capsules in patients with relapsed or refractory peripheral T-cell lymphoma in the dose expansion phase (Part A); in the efficacy evaluation phase with expanded sample size (Part B), the efficacy of SHC014748M capsules in patients with relapsed or refractory peripheral T-cell lymphoma is evaluated based on the objective response rate (ORR). The secondary objective is to evaluate the safety of SHC014748M capsules in patients with relapsed or refractory peripheral T-cell lymphoma.

Start Date27 Aug 2020

Sponsor / Collaborator

Nanjing Sanhome Pharmaceutical Co. Ltd.

NCT04470141 / Unknown statusPhase 2

A Phase II, Multicenter Study to Investigate the Efficacy and Safety of SHC014748M in Patients With Relapsed or Refractory Peripheral T Cell Lymphoma

The purpose of this study is to evaluate the efficacy and safety of SHC014748M in patients with relapsed or refractory relapsed or refractory Peripheral T Cell Lymphoma.

Start Date01 Aug 2020

Sponsor / Collaborator

Nanjing Sanhome Pharmaceutical Co. Ltd.

CTR20200443 / RecruitingPhase 2

SHC014748M胶囊在复发或难治性滤泡性淋巴瘤和边缘区淋巴瘤患者中的有效性和安全性的多中心Ⅱ期临床研究

[Translation] A multicenter phase II clinical study on the efficacy and safety of SHC014748M capsule in patients with relapsed or refractory follicular lymphoma and marginal zone lymphoma

评价SHC014748M胶囊在复发或难治性滤泡性淋巴瘤和边缘区淋巴瘤患者中的有效性和安全性。

[Translation]

To evaluate the efficacy and safety of SHC014748M capsule in patients with relapsed or refractory follicular lymphoma and marginal zone lymphoma.

Start Date23 Jun 2020

Sponsor / Collaborator

Nanjing Sanhome Pharmaceutical Co. Ltd.

100 Clinical Results associated with SHC014748M

100 Translational Medicine associated with SHC014748M

100 Patents (Medical) associated with SHC014748M

Literatures (Medical) associated with SHC014748M

01 Feb 2023·Cancer Chemotherapy and Pharmacology

Mass balance, metabolic disposition, and pharmacokinetics of a novel selective inhibitor of PI3Kδ [14C] SHC014748M in healthy Chinese subjects following oral administration

Article

Author: Xie, Jing ; Guo, Fei ; Liu, Bingyan ; Li, Xiaoli ; Shan, Rongfang ; Ding, Yuzhou ; Su, Yue ; Zhu, Juan ; Xie, Yunqiu ; Zhu, Minhui ; Zhu, Xingyu ; Zhang, Chaoyang ; Wang, Hongju ; Li, Hongtao ; Zhou, Huan ; Xu, Yuanyuan ; Ding, Jiaxiang ; He, Cuixia ; Zhao, Xiangdi ; Fan, Ling ; Ge, Qin ; Wang, Haidong ; Wang, Ying

PURPOSESHC014748M is a potent, novel selective PI3Kδ isoform inhibitor and is proposed for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. This study investigated the pharmacokinetics, mass balance, metabolism and excretion of SHC014748M in Chinese male subjects following a single oral dose of 150 mg (100 μCi) [¹⁴C] SHC014748M.METHODSSix healthy Chinese male subjects administrated an oral suspension of 150 mg (100 μCi) [¹⁴C] SHC014748M and the samples of blood, urine and feces were collected for measuring. Liquid chromatography-tandem mass spectrometry and liquid scintillation counter were utilized to obtain mass balance and the pharmacokinetic data.RESULTSThe median T_max for [¹⁴C]-radioactivity was 1.6 ± 0.5 h after the oral administration of [¹⁴C] SHC014748M and the mean C_max was 3863 ± 354 ng Eq./mL in plasma, while the mean C_max, t_1/2 values and AUC_0-∞ values for total radioactivity in whole blood were 2466 ± 518 ng Eq./mL, 32.2 ± 30.5 h and 66,236 ± 44,232 h * ng Eq./mL, respectively. Fecal excretion was proposed as the predominant elimination route, accounting for a mean of 90.68 ± 11.38% of the administered dose, whereas the mean urine excretion was 6.00 ± 1.48% within 336 h post-dose. The proposed major metabolic pathway of [¹⁴C] SHC014748M in the human body were as follows: (I) monooxidation, (II) glucuronide acid conjugation, and (III) monoxide-hydrogenation.CONCLUSIONSSHC014748M was absorbed, metabolized and excreted with unchanged SHC014748M as its main circulating component in plasma following oral administration. In addition, it was speculated that fecal excretion was the principal excretion pathway; meanwhile, monohydroxy, glucuronide conjugation, oxygen, and hydrogenation were the major clearance pathways of SHC014748M through urine and/or feces.TRIAL REGISTRATIONThe trial registration number: CTR20202505.

01 Dec 2020·NeoplasiaQ2 · MEDICINE

SHC014748M, a novel selective inhi-bitor of PI3Kδ, demonstrates promising preclinical antitumor activity in B cell lymphomas and chronic lymphocytic leukemia

Q2 · MEDICINE

ArticleOA

Author: Cao, Lei ; Xu, Wei ; Li, Jianyong ; Wang, Chao ; Liu, Xiaorong ; Wang, Zhiqiang ; Zhao, Liwen ; Fan, Lei ; Zhang, Xian

PI3Kδ (phosphatidylinositol 3-kinase-δ), one of the class I PI3Ks, is found expressed primarily in leukocytes and plays an essential role in B-cell development and function. This provides a rationale for the development of small molecule inhibitors that selectively target p110δ for patients with indolent non-Hodgkin lymphomas. Here in this paper, we comprehensively evaluated the in vitro and in vivo antitumor activity of SHC014748M, an oral selective inhibitor of PI3Kδ under Phase I clinical evaluation. Biochemical and cell-based assays were used to measure compound potency and selectivity in lymphoma cell lines as well as primary chronic lymphocytic leukemia (CLL) cells. Scid mice were subcutaneously inoculated with the SU-DHL-6 cell line. SHC014748M was more selective for PI3Kδ inhibition relative to other class I PI3K enzymes and showed in vitro activity in most of 23 B lymphoma cell lines and primary CLL cells. SHC014748M also inhibited phosphorylation of AKT, targets downstream of PI3Kδ, in both lymphoma cells and primary CLL cells. In vivo study revealed that SHC014748M significantly reduced lymphoma cell growth in the treatment group compared with control mice. CCL4, CCL17, CCL22 and CXCL13 in patient serum decreased sharply after SHC014748M treatment. According to the results, SHC014748M appeared to be a novel promising compound in the treatment of B cell lymphomas and CLL.

100 Deals associated with SHC014748M

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic Lymphocytic Leukemia	Phase 2	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	19 Jul 2022
Small Lymphocytic Lymphoma	Phase 2	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	19 Jul 2022
Recurrent Peripheral T-Cell Lymphoma, Not Otherwise Specified	Phase 2	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	27 Aug 2020
Marginal Zone B-Cell Lymphoma	Phase 2	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	09 May 2020
Indolent Non-Hodgkin Lymphoma	Phase 1	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	08 Dec 2020
B-Cell Malignant Neoplasm	Phase 1	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	07 Sep 2018
Refractory Indolent Non-Hodgkin Lymphoma	IND Approval	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	20 Nov 2023
Peripheral T-Cell Lymphoma	Discovery	-	Nanjing Sanhome Pharmaceutical Co. Ltd.	01 Aug 2020
T-cell lymphoma recurrent	Discovery	-	Nanjing Sanhome Pharmaceutical Co. Ltd.	01 Aug 2020
Refractory Follicular Lymphoma	Discovery	CN	Nanjing Sanhome Pharmaceutical Co. Ltd.	09 May 2020

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03588598 (ASH2019) Manual	Phase 1	Indolent B-Cell Non-Hodgkin Lymphoma	38	SHC014748M	(thznbmnklh) = none jtlgvsbgsc (eulaosusve ) View more	Positive	13 Nov 2019

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