Amgen/BeiGene's First-in-Class CD3/STEAP1 Bispecific Antibody AMG 509 Enters Phase I Clinical Trial in China for Metastatic Castration-Resistant Prostate Cancer

Dec 20, 2023 15:13 CST Updated 15:13

BeOne

Developer of Molecular Targeted and Immune Anti-Tumor Drugs

Amgen

Developer of Treatment Drugs for Serious Diseases

Recently, Amgen/BeOne Medicines initiated the Phase I clinical trial of the CD3/STEAP1 bispecific antibody AMG 509 for the first time on the CDE Clinical Trial Registration and Information Disclosure Platform.Metastatic Castration-Resistant Prostate Cancer (mCRPC)。

AMG 509 is the world's first and currently the only CD3/STEAP1 bispecific antibody to enter the clinical stage.

Source: CDE Official Website

AMG 509 Is aCD3/STEAP1 Bispecific Antibody，Can bind to the STEAP1 antigen in humans and primates as well as the CD3 receptor on the surface of T cells.

Prostate Transmembrane Epithelial Antigen 1 (STEAP1) is a cell surface antigen induced by androgens and highly expressed in prostate cancer. STEAP1 is also highly expressed in Ewing's sarcoma (EWS) and forms the EWS/FLI1 fusion, which is the primary oncogenic driver of this malignant tumor.

In terms of structural design, Amgen utilized Xencor's Xmab 2+1 asymmetric technology, which also extended the half-life of this protein.

AMG 509 was approved for clinical trials in China for the first time in June this year and initiated its first clinical trial today.. Overseas,According to the Insight database, Amgen is currently conducting a Phase I clinical trial of AMG 509 for the treatment of castration-resistant prostate cancer (Registration Number: NCT04221542). The trial was initiated in March 2020 and is expected to complete its primary endpoint in June 2026. Interim analysis data presented at the 2023 ESMO conference has already shown positive results, as detailed in the figure below:

NCT04221542 Interim Results

Source: Insight Database Web Version (Same as below)

BeOne Medicines and Amgen reached a global oncology strategic partnership in November 2019, collaborating with Amgen to develop includingTarlatamab20 oncology pipeline drugs, includingAccording to the Insight database, in the bispecific antibody project合作的双抗项目中,BeOne Medicines has advanced 7 bispecific antibodies to the clinical development stage in China.

BeOne Medicines/Amgen Co-develop 7 Bispecific Antibodies Entering Clinical Trials in China

The fastest development progress isBlinatumomab andTarlatamab。

Blinatumomab(Blinatumomab, Blincyto®)It is a bispecific CD19-directed CD3 T-cell engager (BiTE®), with one end binding to CD19 expressed on the surface of B-lineage cells and the other end binding to CD3 expressed on the surface of T cells.

BlinatumomabIn China, it was approved for marketing in December 2020 for the treatment of adult patients with relapsed or refractory (R/R) precursor B-cell acute lymphoblastic leukemia (ALL). Subsequently, in May of last year, the indication population was expanded to include pediatric patients.

DLL3/CD3 Bispecific Antibody Tarlatamab/AMG757 just announced new developments last week, with Tarlatamab's BLA application accepted by the FDA and granted priority review status for advanced NSCLC. The PDUFA decision date is June 12, 2024. It is expected to become the world's first.DLL3/CD3 Bispecific Antibody。For more details, see Insight's previous reports>>>World's First! Amgen's DLL3/CD3 Bispecific Antibody Receives FDA Priority Review

In China, Tarlatamab has entered the Phase III clinical stage in July.LaunchedPhase III DeLLphi-304 Study in China(Registration No.: CTR20232049), aimed to evaluateEfficacy and Safety of Tarlatamab versus Standard Therapy in Subjects with Relapsed Small Cell Lung Cancer after First-Line Platinum-Based Chemotherapy. The planned global number of subjects is 700, with 107 in China, and the enrollment of the first subject in China was completed in September.

Phase I Clinical Trial Results of Tarlatamab for Relapsed or Refractory SCLC Show:In patients who had previously received a median of 2 lines of treatment, including 49.5% of patients who had been treated with anti-PD-1/L1 inhibitors,ORR was 23.4%，mDoR was 12.3 months, DCR was 51.4%, mPFS and mOS were 3.7 months and 13.2 months, respectively. In terms of safety, the incidence of TRAE of any grade was 90.7%, and the incidence of TRAE ≥ grade 3 was 30.8%; the maximum tolerated dose was not reached.

Moreover, the data presented at the 2023 ASCO meeting indicated that Tarlatamab showed encouraging efficacy and safety in ES-SCLC patients, regardless of the presence of BM.

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