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CD19 inhibition

CompoundSurovatamig (AZD0486)

Area under investigation

B-ALL, B-Cell non-Hodgkin lymphoma, FL, CLL, DLBCL/LBCL, MCL

Scientific PillarT-Cell Engager

Target Overview

CD19 is a pan B-cell marker which is recognized as an immunotherapy target for multiple B cell malignancies and autoimmune diseases.1,2 CD19 targeted agents, including antibodies, ADCs and CARTs are approved for multiple B cell cancers.3

Compound Overview

Surovatamig (formerly TNB-486 and AZD0486) is a potent, bispecific T-cell engager (TCE) that binds to CD19 preferentially and engages the T cells through CD3 moiety (CD19xCD3).4 

High-affinity CD19 domain of Surovatamig binds the tumor cells, while the low-affinity CD3 binding recruits T cells resulting in target cell lysis.4

Mechanism of Action

  • Mechanism of Action

MoA image adapted from Malik-Chaudhry et al MAbs (2021).

References

1. Hammer O. MAbs. 2012;4(5):571-577. 2. Gambella M, Carlomagno S, Raiola AM, et al. Front Immunol. 2022;13:837457. 3. Viardot A, Locatelli F, Stieglmaier J, et al. Ann Hematol. 2020;99(10):2215-2229. 4. Malik-Chaudhry HK, Prabhakar K, Ugamraj HS, et al. MAbs. 2021;13(1):1890411.

Target Overview

CD19 is a pan B-cell marker which is recognized as an immunotherapy target for multiple B cell malignancies and autoimmune diseases.1,2 CD19 targeted agents, including antibodies, ADCs and CARTs are approved for multiple B cell cancers.3

Compound Overview

Surovatamig (formerly TNB-486 and AZD0486) is a potent, bispecific T-cell engager (TCE) that binds to CD19 preferentially and engages the T cells through CD3 moiety (CD19xCD3).4 

High-affinity CD19 domain of Surovatamig binds the tumor cells, while the low-affinity CD3 binding recruits T cells resulting in target cell lysis.4

Mechanism of Action

  • Mechanism of Action

MoA image adapted from Malik-Chaudhry et al MAbs (2021).

References

1. Hammer O. MAbs. 2012;4(5):571-577. 2. Gambella M, Carlomagno S, Raiola AM, et al. Front Immunol. 2022;13:837457. 3. Viardot A, Locatelli F, Stieglmaier J, et al. Ann Hematol. 2020;99(10):2215-2229. 4. Malik-Chaudhry HK, Prabhakar K, Ugamraj HS, et al. MAbs. 2021;13(1):1890411.

Clinical trial information


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Area under investigation=true,B-ALL,B-Cell non-Hodgkin lymphoma,FL,CLL,DLBCL/LBCL,MCL

NCT04594642 trial overview

Tumor

R/R B-NHL

Trial Identifier

NCT04594642

Phase

I

Regimen

Surovatamig

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SOUNDTRACK-B trial overview

Tumor

Relapsed/refractory B-cell NHL or FL and LBCL

Trial Identifier

NCT06526793

Phase

II

Regimen

Surovatamig monotherapy

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SOUNDTRACK-C1 trial overview

Tumor

CLL/SLL with uIGHV

Trial Identifier

NCT07509151

Phase

III

Regimen

Surovatamig consolidation therapy

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SOUNDTRACK-D2 trial overview

Tumor

Newly diagnosed LBCL

Trial Identifier

NCT07215585

Phase

III

Regimen

Surovatamig; R-mini-CHOP

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SOUNDTRACK-E trial overview

Tumor

R/R CLL/SLL, MCL, and LBCL

Trial Identifier

NCT06564038

Phase

I/II

Regimen

Sub-study 1 (RR CLL/SLL): surovatamig IV or SC; sub-study 2 (RR MCL): surovatamig IV or SC; sub-study 3 (RR LBCL): surovatamig IV + R-CHOP

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SOUNDTRACK-F1 trial overview

Tumor

Previously untreated follicular lymphoma

Trial Identifier

NCT06549595

Phase

III

Regimen

Surovatamig + rituximab; SoC Immunochemotherapy

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SYRUS trial overview

Tumor

Relapsed/refractory B-cell acute lymphoblastic leukemia

Trial Identifier

NCT06137118

Phase

I/II

Regimen

Surovatamig monotherapy

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Abbreviations

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  • B-ALL

    B-cell acute lymphoblastic leukemia

  • BR

    bendamustine/rituximab

  • CAR-T

    chimeric antigen receptor T cell (therapy)

  • CD19

    cluster of differentiation 19

  • CD3

    cluster of differentiation 3

  • CLL

    chronic lymphocytic leukemia

  • CNS

    central nervous system

  • CR

    complete response

  • CRR

    complete response rate

  • DLBCL

    diffuse large B-cell lymphoma

  • DoCR

    duration of complete response

  • DoR

    duration of response

  • DOSRI

    Dose Optimisation and Safety run-in

  • EBV

    Epstein-Barr virus

  • ECOG

    Eastern Cooperative Oncology Group

  • ECOG-PS

    Eastern Cooperative Oncology Group performance status

  • Fc

    fragment crystallizable region

  • FDG

    fluorodeoxyglucose

  • FL

    Follicular lymphoma

  • GELF

    Groupe d'Étude des Lymphomes Folliculaires

  • HBV

    Hepatitis B Virus

  • HCV

    Hepatitis C Virus

  • HGBL

    High grade B-cell lymphoma

  • HIV

    Human Immunodeficiency Virus

  • HLH

    Heamophagocytic lymphohistiocytosis

  • ICF

    informed consent form

  • IGHV

    immunoglobulin heavy chain variable region

  • IV

    intravenous

  • LBCL

    large b-cell lymphoma

  • MCL

    mantle cell lymphoma

  • MDS

    myelodysplastic syndrome

  • MM

    multiple myeloma

  • MOA

    mechanism of action

  • NHL

    Non-Hodgkin Lymphoma

  • ORR

    overall or objective response rate

  • OS

    overall survival

  • PFS

    progression-free survival

  • PFS2

    time from randomization to second progression or death

  • ph3

    Phase 3

  • PK

    pharmacokinetics

  • R-CHOP

    rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone

  • RCVP

    rituximab + cyclophosphamide + vincristine + prednisone

  • RP3D

    recommended phase 3 dose

  • R/R

    relapsed/refractory

  • SC

    subcutaneous

  • SLL

    Small Lymphocytic Lymphoma

  • SoC

    standard of care

  • TCE

    T-cell engager

  • TFST

    time to first subsequent therapy or death

  • WHO

    World Health Organization

Some compounds herein refer to selected AstraZeneca pipeline products still under development. AstraZeneca pipeline products are investigational products and, as such, are not approved by the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory agency for the uses under investigation. Information regarding these investigational products should, under no circumstances, be regarded as a recommendation for their use or of their safety or efficacy.

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Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
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