Bristol Myers Squibb’s Novel CELMoD Agent Golcadomide Capsules Approved for Clinical Trial in China for Untreated High-Risk Large B-Cell Lymphoma
Bristol-Myers Squibb
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On June 12, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced that Bristol-Myers Squibb'sCelgene's Class 1 New Drug ApplicationgOlcadomide CapsulesApproved for clinical use, intended to be developed forUntreated high-risk large B-cell lymphoma。According to public data from Bristol-Myers Squibb, golcadomide is aNovel E3 Ubiquitin Ligase Cereblon (CELMoD) Molecules, which has already entered Phase 3 clinical trials on an international scale.In the phase 1/2 clinical study targeting B-cell lymphoma,The objective response rate (ORR) of this product reached 91.1%.
Screenshot source: CDE official website
Public information shows that Bristol-Myers Squibb Company's Protein Homeostasis technology platform uses a variety of different methods to achieve the degradation of target proteins, including molecular glue compounds known as CELMoD.They work by binding to the E3 ubiquitin ligase Cereblon, altering its substrate specificity so that it can tag cancer-related proteins, prompting their degradation.Based on this platformMultiple CELMoD products have entered the clinical development stage, including the one approved for clinical use this time.gOlcadomide Capsules (CC-99282),This product is targeted atNon-Hodgkin's Lymphoma (NHL)The characteristics of the disease have been optimized, making it mainly distributed in lymphoid organs.。
▲Golcadomide Capsule Product Features (Image Source: Reference [2])
In December 2023, Bristol-Myers Squibb announced the early study results of golcadomide at the American Society of Hematology (ASH) Annual Meeting. Among themCC-220-DLBCL-001 StudyIs a dose-expansion phase study of a Phase 1b trial, exploring the combination of golcadomide with R-CHOP inPatients with previously untreated aggressive B-cell lymphomaThe activity and safety were evaluated. Patients were randomized 1:1 to receive one of two recommended Phase 2 dose levels plus R-CHOP-21, administered in a fixed regimen of 6 cycles.
According to the public information on the ASH official website, the research results showed that, with a median follow-up time of 4.1 months, among all patients who responded at the end of treatment,21/25 (84%) achievedComplete Metabolic Response Rate (CMR)；Total14/14 (100%) Acceptedgolcadomide Patients treated with a 0.4mg dose achieved CMR at the end of treatment.。In evaluable patients (n=56), the ORR was 91.1%.In addition,In both dose groups, golcadomide at steady-state levels reduced Ikaros by more than 80%, achieving the anticipated optimized tumor cell killing and stimulating T cells and NK cells.
▲Bristol-Myers Squibb CompanyBased onNew molecules developed by the protein homeostasis technology platform(Image source: Reference [2])
According to publicly available information from Bristol-Myers Squibb, golcadomide represents one of the core products of the company's differentiated targeted protein degradation research platform. In addition to this drug,Bristol-Myers Squibb has multiple targeted protein degraders that have entered the clinical research stage in China, such asCC-92480（mezigdomide）、Iberdomide CapsulesHave already initiated Phase 3 clinical trials in China, and the indications they target areMultiple Myeloma. In addition, on an international scale, Bristol-Myers Squibb CompanyMolecular Glue-Type Protein Degrader CC-90009 Targeting GSPT1、MaleHormone Receptor (AR) Degrader AR-LDD, CK1α Degrader for Hematologic MalignanciesIt is also being explored in Phase 1 clinical trials.
[2]Bristol Myers Squibb Investor Event. Retrieved November 19, 2021, from https://s21.q4cdn.com/104148044/files/doc_presentations/2021/2021-BMS-Investor-Event-Presentation.pdf
[3]Golcadomide (GOLCA; CC-99282), a Novel CELMoD Agent, Plus R-CHOP in Patients (pts) with Previously Untreated Aggressive B-Cell Lymphoma (a-BCL): Safety and Efficacy Results from Phase 1b Dose Expansiont. Retrieved November 02, 2023, from https://ashpublications.org/blood/article/142/Supplement%201/4459/500493/Golcadomide-GOLCA-CC-99282-a-Novel-CELMoD-Agent
[4]Bristol-Myers Squibb Pipeline. From https://www.bms.com/researchers-and-partners/in-the-pipeline.html
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