Delving into the Latest Updates on LP-118 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Bcl-2 x Bcl-xl

Mechanism

Bcl-2 inhibitors(Apoptosis regulator Bcl-2 inhibitors), Bcl-xl inhibitors(Apoptosis regulator Bcl-X inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesNervous System Diseases+ [4]

Active Indication

Non-Hodgkin LymphomaSolid tumorAdvanced cancer+ [13]

Inactive Indication-

Originator Organization

Guangzhou Lupeng Pharmaceutical Co., Ltd.

Active Organization

Newave Pharmaceutical Inc.

Guangzhou Lupeng Pharmaceutical Co., Ltd.

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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The purpose of this study is to learn more about LP-118 (an experimental drug) and its side effects and decide on acceptable doses. The purpose of this study is to determine if LP-118 can be given safely with another medicine called ponatinib, that is FDA-approved for the treatment of acute lymphoblastic leukemia.

Start Date13 Sep 2024

Sponsor / Collaborator

The University of Chicago

NCT05025358

/ Active, not recruitingPhase 1

A Phase I Study on Safety, Tolerance, Pharmacokinetics and Preliminary Efficacy of LP-118 in Patients with Advanced Malignancies

This is a phase I, multi-center, open-label, dose escalation study to evaluate the safety, tolerability, pharmacokinetics and clinical activity of LP-118 in patients with advanced malignancies, including solid tumors and lymphomas. LP-118 is a BCL-2/BCL-XL small molecule inhibitor.

Start Date14 Sep 2021

Sponsor / Collaborator

Guangzhou Lupeng Pharmaceutical Co., Ltd.

CTR20211648

/ RecruitingPhase 1

评估口服BCL-2/BCL-XL抑制剂LP-118在中国晚期恶性肿瘤患者的安全性、耐受性、药代动力学特征以及初步疗效的I期临床研究

[Translation] A Phase I clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of LP-118, an oral BCL-2/BCL-XL inhibitor, in Chinese patients with advanced malignancies

1. 评估LP-118在中国晚期恶性肿瘤患者中的安全性和耐受性，评估剂量限制性毒性（DLT）和最大耐受剂量（MTD），并推荐II期临床研究的剂量和给药方式（RP2D）。 2. 评价单剂量和多剂量口服LP-118在中国晚期恶性肿瘤患者中的人体药代动力学（PK）特征和食物影响。 3. 初步评估LP-118单药治疗晚期恶性肿瘤的客观缓解率（ORR）、疾病控制率（DCR）、缓解持续时间（DOR）、无进展生存期（PFS）以及总生存期（OS）。

[Translation]

1. To evaluate the safety and tolerability of LP-118 in Chinese patients with advanced malignancies, assess the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), and recommend the dose and administration method (RP2D) for Phase II clinical studies. 2. To evaluate the human pharmacokinetic (PK) characteristics and food effects of single-dose and multiple-dose oral LP-118 in Chinese patients with advanced malignancies. 3. To preliminarily evaluate the objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) of LP-118 monotherapy for advanced malignancies.

Start Date08 Sep 2021

Sponsor / Collaborator

Guangzhou Lupeng Pharmaceutical Co., Ltd.

100 Clinical Results associated with LP-118

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100 Translational Medicine associated with LP-118

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100 Patents (Medical) associated with LP-118

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1

Literatures (Medical) associated with LP-118

Haematologica

LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor that demonstrates efficacy in models of venetoclax-resistant chronic lymphocytic leukemia

Article

Author: Perry, Elizabeth ; Shen, Yue ; Diaz-Rohena, Daisy Y ; Ravikrishnan, Janani ; Bhat, Seema A ; Anthony, Stephen P ; Chen, Yi ; Chen, Yu ; Wierda, William G ; Satpati, Suresh ; Lapalombella, Rosa ; Misra, Shrilekha ; Mitchell, Andrew ; Woyach, Jennifer A ; Davids, Matthew S ; Sampath, Deepa ; Mo, Xiaokui ; Lozanski, Arletta ; Rogers, KerryA ; Sanchez, John ; Lai, Tzung-Huei ; Kittai, Adam S ; Kaufman, Tierney ; Lozanski, Gerard ; Williams, Charmelle D ; Collins, Mary C ; Jain, Nitin ; Byrd, John C ; Liu, Chaomei ; Tan, Fenlai ; Muhowski, Elizabeth

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the Bcell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis in both venetoclax naïve and resistant CLL cells. Significantly, LP-118 is effective in cell lines expressing the BCL2 G101V mutation and in cells expressing BCLXL but lacking BCL2 dependence. Using an immunocompetent mouse model, Eμ-TCL1, LP-118 demonstrates low platelet toxicity, which hampered earlier BCLXL inhibitors. Finally, LP-118 in the RS4;11 and OSU-CLL xenograft models results in decreases in tumor burden and survival advantage, respectively. These results provide a mechanistic rationale for the evaluation of LP-118 for the treatment of venetoclax responsive and relapsed CLL.

100 Deals associated with LP-118

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Phase 1	US	Newave Pharmaceutical Inc.	23 Aug 2021
Chronic lymphocytic leukaemia refractory	Phase 1	US	Newave Pharmaceutical Inc.	23 Aug 2021
Chronic Myelomonocytic Leukemia	Phase 1	US	Newave Pharmaceutical Inc.	23 Aug 2021
Multiple Myeloma	Phase 1	US	Newave Pharmaceutical Inc.	23 Aug 2021
Myelodysplastic Syndromes	Phase 1	US	Newave Pharmaceutical Inc.	23 Aug 2021
Myelofibrosis	Phase 1	US	Newave Pharmaceutical Inc.	23 Aug 2021
Myeloproliferative Disorders	Phase 1	US	Newave Pharmaceutical Inc.	23 Aug 2021
Refractory Adult Acute Lymphoblastic Leukemia	Phase 1	US	Newave Pharmaceutical Inc.	23 Aug 2021
Small Lymphocytic Lymphoma	Phase 1	US	Newave Pharmaceutical Inc.	23 Aug 2021
T-Cell Prolymphocytic Leukemia	Phase 1	US	Newave Pharmaceutical Inc.	23 Aug 2021