AbbVie Launches Phase 3 Trial in China for Monthly-Dosed Bispecific Antibody ABBV-383 in Relapsed/Refractory Multiple Myeloma

▎Edited by the WuXi AppTec content team

Screenshot Source：China Drug Clinical Trial Registration and Information Disclosure Platform Official Website

Multiple Myeloma (MM) is an incurable blood cancer, and almost all patients will experience recurrence, requiring subsequent treatment. As the disease progresses, each recurrence becomes more aggressive, and the remission periods achieved by new therapies gradually shorten.B-Cell Maturation Antigen（BCMA) is a member of the TNF receptor superfamily, mainly expressed in MM cell lines and cells of MM patients, with expression increasing as the disease progresses, making it an ideal therapeutic target for MM.

ABBV-383 is an investigational BCMA x CD3 bispecific antibody T-cell engager developed by AbbVie,Composed of a bivalent high-affinity BCMA binding domain and a low-affinity CD3 binding domain, aimed at reducing the risk of cytokine release syndrome (CRS). It also includes a silent Fc tail designed to extend half-life, supporting once every 4 weeks (Q4W) dosing., thereby improving patient convenience and reducing the treatment burden on patients.

According to previously published data, ABBV-383 yielded safety and efficacy results in the first-in-human Phase 1 study in patients with relapsed/refractory multiple myeloma. The data showed,At doses of 40mg and 60mg,ABBV-383 monotherapy induced deep and durable responses, with median progression-free survival (mPFS) of 13.7 months and 11.2 months, and 12-month duration of response (DOR) rates of 70% and 66%, respectively.. In addition60mg Q4W GroupPatient'sObjective Response Rate (ORR)For65%。The phase 1 clinical study results of ABBV-383 were successively published at the 2023 American Society of Hematology (ASH) Annual Meeting and the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

In June 2024, AbbVie announced the first patient dosing in the Phase 3 clinical study of ABBV-383. The Phase 3 trial, named CERVINO, will evaluate ABBV-383.Single-agent monthly administrationEfficacy, safety, and tolerability of standard available therapies (SATs) in RRMM patients who have received at least two prior treatments. The two primary endpoints are progression-free survival and overall response rate.According to the results of the Phase 1 study,The researchers will select60mg Q4W of ABBV-383 monotherapy as the optimal dose in Phase 3 clinical study。

In addition to targeting multiple myeloma,ABBV-383 is also expected to be used for the treatmentImmunoglobulin Light Chain Amyloidosis,It is currently in Phase 1 clinical trials for this indication.

Public information shows that, in addition to AbbVie'sABBV-383，Globally, multiple BCMA/CD3 bispecific antibody therapies have been approved for marketing or have entered the late-stage research phase. Among them, Johnson & Johnson's subcutaneous injectionTelituximab InjectionHas been approved for marketing in China, the productSupplemental Biologics License Application Also Received FDA ApprovalApproval，For reducing the dosing frequency to once every two weeks in RRMM patients; Pfizer's subcutaneous injection BCMA×CD3 bispecific antibody elranatamab has been approved for marketing by the U.S. FDA, and an application for marketing has also been submitted in China and included.Priority Review; Regeneron's linvoseltamab marketing application has been granted by the FDAPriority Review Status；Bristol-Myers Squibb's Alnuctamab has also initiated Phase 3 clinical research in May this year.

[1] Official Website of China Drug Clinical Trial Registration and Information Disclosure Platform. From http://www.chinadrugtrials.org.cn/index.html

[2]AbbVie Advances Oncology Pipeline With Start of Multiple Myeloma Phase 3 Clinical Trial for Investigational Asset ABBV-383.Retrieved Jun 05，2024, From https://news.abbvie.com/2024-06-05-AbbVie-Advances-Oncology-Pipeline-With-Start-of-Multiple-Myeloma-Phase-3-Clinical-Trial-for-Investigational-Asset-ABBV-383

[3]Updated Safety and Efficacy Results of Abbv-383, a BCMA x CD3 Bispecific T-Cell Redirecting Antibody, in a First-in-Human Phase 1 Study in Patients with Relapsed/Refractory Multiple Myeloma.Retrieved Nov 2，2023, From https://ashpublications.org/blood/article/142/Supplement%201/3378/503592/Updated-Safety-and-Efficacy-Results-of-Abbv-383-a

[4]Efficacy, safety, and determination of RP2D of ABBV-383, a BCMA bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). Retrieved May 29，2024, From https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7531