Delving into the Latest Updates on Circularly Permuted TRAIL with Synapse

Overview

Basic Info

Drug Type

Cytokines

Synonyms

CPT (Hiteck Biological), Human recombinant Apo2L/TRAIL, 重组变构人肿瘤坏死因子相关凋亡诱导配体 (海特生物)

+ [1]

Target

DR4 x DR5

Mechanism

DR4 agonists(Tumor necrosis factor receptor superfamily member 10A agonists), DR5 agonists(Tumor necrosis factor receptor superfamily member 10B agonists)

Therapeutic Areas

NeoplasmsImmune System DiseasesCardiovascular Diseases+ [1]

Active Indication

Multiple Myeloma

Inactive Indication-

Originator Organization

Wuhan Hiteck Biological Pharma Co., Ltd.

Active Organization

Wuhan Hiteck Biological Pharma Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (01 Nov 2023),

Multiple Myeloma

Regulation-

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主要目的是评价CPT联合沙利度胺和地塞米松（TD方案）与单用TD方案相比治疗复发或难治的多发性骨髓瘤患者是否具有更好的疗效，主要观察指标是无进展生存期（PFS）。次要目的是评价CPT与沙利度胺和地塞米松（TD方案）联合用药的安全性。

[Translation]

The primary objective was to evaluate whether CPT combined with thalidomide and dexamethasone (TD regimen) has better efficacy than TD regimen alone in the treatment of patients with relapsed or refractory multiple myeloma, and the primary observation indicator is progression-free survival (PFS). The secondary objective was to evaluate the safety of CPT combined with thalidomide and dexamethasone (TD regimen).

Start Date25 Feb 2015

Sponsor / Collaborator

Beijing Shadong Biotechnology Co., Ltd.

ChiCTR-IPR-15006024 / RecruitingPhase 3IIT

A Multicenter, Randomized, Double-Blind, Controlled Phase III Study of CPT or Placebo in Combination with Thalidomide and Dexamethasone in Subjects with Relapsed or Refractory Multiple Myeloma

Start Date01 Jan 2015

Sponsor / Collaborator-

100 Clinical Results associated with Circularly Permuted TRAIL

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100 Translational Medicine associated with Circularly Permuted TRAIL

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100 Patents (Medical) associated with Circularly Permuted TRAIL

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8

Literatures (Medical) associated with Circularly Permuted TRAIL

01 Nov 2014·American Journal of HematologyQ1 · MEDICINE

A multicenter, open‐label phase II study of recombinant CPT (Circularly Permuted TRAIL) plus thalidomide in patients with relapsed and refractory multiple myeloma

Q1 · MEDICINE

Article

Author: Geng, Chuanying ; Yang, Shifang ; Chen, Wen‐Ming ; Wang, Zhao ; Hou, Jian ; Qiu, Lugui ; Zhao, Yaozhong ; Wang, Fuxu ; Huang, Zhongxia ; Liu, Yan ; Ke, Xiaoyan ; Zheng, Xiangjun ; Xi, Hao ; Wei, Peng ; Zhu, Bing ; Wei, Na

Circularly permuted TRAIL (CPT), a recombinant mutant of human Apo2L/TRAIL, is a novel antitumor candidate for multiple myeloma (MM) and other hematologic malignancies. In this phase II study, the safety and efficacy of CPT plus thalidomide was investigated in thalidomide‐resistant MM patients. A total of 43 patients were recruited into three CPT plus thalidomide cohorts based on CPT dosage in sequence: 5 mg/kg (n = 11), 8 mg/kg (n = 17), and 10 mg/kg (n = 15). CPT was administered via intravenous infusion on days 1–5, and thalidomide was given orally at 100 mg once daily in each 21‐day cycle. The overall response rate (ORR) of 41 efficacy‐evaluable patients was 22.0% (2 complete response, 3 near complete response, and 4 partial response). No significant difference in the ORR was observed among the three dose cohorts; however, the ORR tended to be higher with the higher‐dose regimen. Median progression‐free survival and median duration of response were 6.6 months and 6.1 months, respectively. The most common treatment‐related adverse events (TRAEs) were neutropenia (46.5%), leukopenia (41.9%), fever (37.2%), elevated AST (32.6%), and elevated ALT (20.9%). TRAEs of Grade 3–4 were mainly neutropenia (18.6%), anemia (9.3%), elevated AST (7.0%), and leukopenia (4.7%). No significant differences were found in the incidence and severity of TRAEs among the three cohorts. In conclusion, CPT plus thalidomide was well tolerated with no occurrence of dose‐limiting toxicities and demonstrated promising antitumor activity in RRMM patients. CPT at 10 mg/kg for 5 days in combination with thalidomide and dexamethason will be studied in the next clinical trial. Am. J. Hematol. 89:1037–1042, 2014. © 2014 Wiley Periodicals, Inc.

01 Feb 2011·Journal of Pharmaceutical SciencesQ3 · MEDICINE

Preparation and Characterization of Apo2L/TNF-Related Apoptosis-Inducing Ligand–Loaded Human Serum Albumin Nanoparticles with Improved Stability and Tumor Distribution

Q3 · MEDICINE

Article

Author: Hye Suk Lee ; Yu Seok Youn ; Chan Woong Park ; Tae Hyung Kim ; Sung Mook Lim ; Hai-Hua Jiang ; Kang Choon Lee ; Kyung Kook Tak ; Cheng-Hao Jin

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has received considerable attention as a potential anticancer agent. However, recombinant Apo2L/TRAIL has several limitations, which include a weak pharmacokinetic profile, namely, a short biological half-life and rapid renal clearance, and an inability to form a homotrimeric structure. In this research, we attempted to develop a sustained release nanoparticle (NP) formulation that stabilizes Apo2L/TRAIL and preserves its antitumor activity. Apo2L/TRAIL-loaded human serum albumin (HSA) NPs were prepared using a desolvation technique optimized by particle size, zeta-potential, and entrapment efficiency. Apo2L/TRAIL in HSA-NPs continuously released over 24 h at 37°C in phosphate buffered saline and rat plasma condition, and the biological activity of Apo2L/TRAIL-HSA-NPs was preserved (IC(50) = 67.2 ng/mL versus Apo2L/TRAIL IC(50) = 55.4 ng/mL) with negligible activity loss. Furthermore, in vivo pharmacokinetic profiles and tumor distribution demonstrated the superiority of Apo2L/TRAIL-HSA-NPs over Apo2L/TRAIL. The circulating half-life period was significantly prolonged from 9.8 to 90.7 min (9.2-fold enhancement), and drug bioavailability was clearly enhanced on the basis of area under the curve analysis (2.7-fold). And tumor distribution of Apo2L/TRAIL-HSA-NPs was also increased at 1 h after injection, which was about 14-fold (1-h point) over that of Apo2L/TRAIL. These results show that Apo2L/TRAIL-loaded HSA-NPs should be considered as potential long-acting cancer agents.

15 Mar 2009·Clinical Cancer ResearchQ1 · MEDICINE

Apo2L/TRAIL Inhibits Tumor Growth and Bone Destruction in a Murine Model of Multiple Myeloma

Q1 · MEDICINE

Article

Author: Martin, Sally ; Hay, Shelley ; Zinonos, Irene ; Evdokiou, Andreas ; Diamond, Peter ; Labrinidis, Agatha ; Zannettino, Andrew C.W. ; Atkins, Gerald J. ; Liapis, Vasilios ; Ponomarev, Vladimir ; Sims, Natalie A. ; Findlay, David M. ; Vincent, Cristina

AbstractPurpose: Multiple myeloma is an incurable disease, for which the development of new therapeutic approaches is required. Here, we report on the efficacy of recombinant soluble Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to inhibit tumor progression and bone destruction in a xenogeneic model of human multiple myeloma.Experimental Design: We established a mouse model of myeloma, in which Apo2L/TRAIL-sensitive RPMI-8226 or KMS-11 cells, tagged with a triple reporter gene construct (NES-HSV-TK/GFP/Luc), were transplanted directly into the tibial marrow cavity of nude mice. Tumor burden was monitored progressively by bioluminescence imaging and the development of myeloma-induced osteolysis was measured using high resolution in vivo micro-computed tomography.Results: Tumor burden increased progressively in the tibial marrow cavity of mice transplanted with Apo2L/TRAIL-sensitive RPMI-8226 or KMS-11 cells associated with extensive osteolysis directly in the area of cancer cell transplantation. Treatment of mice with recombinant soluble Apo2L/TRAIL reduced myeloma burden in the bone marrow cavity and significantly protected against myeloma-induced osteolysis. The protective effects of Apo2L/TRAIL treatment on bone were mediated by the direct apoptotic actions of Apo2L/TRAIL on myeloma cells within the bone microenvironment.Conclusions: This is the first in vivo study that investigates the efficacy of recombinant Apo2L/TRAIL on myeloma burden within the bone microenvironment and associated myeloma-induced bone destruction. Our findings that recombinant soluble Apo2L/TRAIL reduces myeloma burden within the bone microenvironment and protects the bone from myeloma-induced bone destruction argue against an inhibitory role of osteoprotegerin in Apo2L/TRAIL-induced apoptosis in vivo and highlight the need to clinically evaluate Apo2L/TRAIL in patients with multiple myeloma.

100 Deals associated with Circularly Permuted TRAIL

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R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Multiple Myeloma	CN	Wuhan Hiteck Biological Pharma Co., Ltd.	01 Nov 2023

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


CTR20140751 (CPT-MM301 , NEWS) Manual	Phase 3	Multiple Myeloma Third line	417	CPT+沙利度胺+地塞米松 (CPT联合TD方案)	(okcqdgcslc) = qecurvrnpm embkjvxhcr (qtxakkfzlm ) View more	Positive	15 Jun 2020
				安慰剂+沙利度胺+地塞米松 (安慰剂联合TD方案)	(okcqdgcslc) = gvlmucbmds embkjvxhcr (qtxakkfzlm ) View more