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PD-1/CTLA-4 dual checkpoint inhibitor bispecific mAb

CompoundVolrustomig

Area under investigation

Advanced solid tumors, BTCs, Cervical cancer, Gastric/GEJ cancer, HCC, HNSCC, Mesothelioma, NSCLC, mCRC

Scientific PillarImmuno-Oncology

Target Overview

Programmed cell death-1 (PD-1) is a cell surface receptor that interacts with 2 ligands, programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2), to deliver inhibitory signals to T cells, limiting their function.1

Cytotoxic T–lymphocyte-associated protein 4 (CTLA-4) is expressed exclusively on the surface of effector T cells (Teff) and regulatory T cells (Tregs).1 CTLA-4 serves to inhibit T-cell activation through ligand competition with the costimulatory receptor, CD28.1

PD-1 and CTLA-4 blockade has been shown to potentiate anti-tumor immunity across a number of tumor types.2

Compound Overview

Volrustomig (formerly MEDI5752) is an innovative, investigational, bispecific dual checkpoint inhibitor targeting both CTLA-4 and PD-1. It is designed to deliver coordinated and targeted blockade of PD-1 and CTLA-4 on the same T cell, potentially enhancing immune activation compared to co-administration.3

Volrustomig’s bispecific modality enables:

  • Preferential binding to CTLA‑4 on PD-1-positive T cells, enhancing productive T cell activity3
  • Dose-dependent increase in T cell proliferation that exceeds that of PD-L1 + CTLA-4 inhibitor co-administration4
  • Antitumor immune response that surpasses the outcomes that are achievable with current immunotherapy combinations4,5

Volrustomig is currently being clinically evaluated in the treatment of advanced solid tumors, including Mesothelioma, mNSCLC, HNSCC, Cervical cancer, Gastric/GEJ cancer, advanced solid tumors, BTCs, HCC, mCRC, RCC

Mechanism of Action

  • Mechanism of Action
  • Mechanism of Action

References

1. Pardoll DM. Nat Rev Cancer. 2012;12(4):252-264. 2. Roy D, Gilmour C, Patnaik S, Wang LL. Front Immunol. 2023;14:1264327. 3. Dovedi SJ, Elder MJ, Yang C, et al. Cancer Discov. 2021;11(5):1100-1117. 4. Tran B, Viskoboynik M, Kim S-W, Lemech C. Cancer Res. 2022;82(suppl 12):CT016-CT016. 5. Achour I, Kuziora M, Song F, et al. Presented at: American Association for Cancer Research (AACR) Meeting; April 5–10, 2024; San Diego, CA. Poster 3627)

Target Overview

Programmed cell death-1 (PD-1) is a cell surface receptor that interacts with 2 ligands, programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2), to deliver inhibitory signals to T cells, limiting their function.1

Cytotoxic T–lymphocyte-associated protein 4 (CTLA-4) is expressed exclusively on the surface of effector T cells (Teff) and regulatory T cells (Tregs).1 CTLA-4 serves to inhibit T-cell activation through ligand competition with the costimulatory receptor, CD28.1

PD-1 and CTLA-4 blockade has been shown to potentiate anti-tumor immunity across a number of tumor types.2

Compound Overview

Volrustomig (formerly MEDI5752) is an innovative, investigational, bispecific dual checkpoint inhibitor targeting both CTLA-4 and PD-1. It is designed to deliver coordinated and targeted blockade of PD-1 and CTLA-4 on the same T cell, potentially enhancing immune activation compared to co-administration.3

Volrustomig’s bispecific modality enables:

  • Preferential binding to CTLA‑4 on PD-1-positive T cells, enhancing productive T cell activity3
  • Dose-dependent increase in T cell proliferation that exceeds that of PD-L1 + CTLA-4 inhibitor co-administration4
  • Antitumor immune response that surpasses the outcomes that are achievable with current immunotherapy combinations4,5

Volrustomig is currently being clinically evaluated in the treatment of advanced solid tumors, including Mesothelioma, mNSCLC, HNSCC, Cervical cancer, Gastric/GEJ cancer, advanced solid tumors, BTCs, HCC, mCRC, RCC

Mechanism of Action

  • Mechanism of Action
  • Mechanism of Action

References

1. Pardoll DM. Nat Rev Cancer. 2012;12(4):252-264. 2. Roy D, Gilmour C, Patnaik S, Wang LL. Front Immunol. 2023;14:1264327. 3. Dovedi SJ, Elder MJ, Yang C, et al. Cancer Discov. 2021;11(5):1100-1117. 4. Tran B, Viskoboynik M, Kim S-W, Lemech C. Cancer Res. 2022;82(suppl 12):CT016-CT016. 5. Achour I, Kuziora M, Song F, et al. Presented at: American Association for Cancer Research (AACR) Meeting; April 5–10, 2024; San Diego, CA. Poster 3627)

Clinical trial information


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Area under investigation=true,Advanced solid tumors,BTCs,Cervical cancer,Gastric/GEJ cancer,HCC,HNSCC,Mesothelioma,NSCLC,mCRC

CANTOR trial overview

Tumor

pMMR/MSS mCRC in the absence of liver metastases

Trial Identifier

NCT06792695

Phase

II

Stage

IV, mCRC in the absence of liver metastases

Regimen

Volrustomig + FOLFIRI+ bevacizumab; FOLFIRI + bevacizumab

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DESTINY-Gastric03 trial overview

Tumor

HER2-expressing advanced/metastatic gastric/GEJ and esophageal adenocarcinoma

Trial Identifier

NCT04379596

Phase

Ib/II

Stage

Advanced

Regimen

T-DXd ± (chemotherapy or durvalumab or pembrolizumab); T-DXd + chemotherapy + (durvalumab or pembrolizumab); T-DXd + volrustomig + chemotherapy; T-DXd + rilvegostomig + chemotherapy

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fam-trastuzumab deruxtecan-nxki in US only; trastuzumab deruxtecan in other regions of world.

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DESTINY-Lung03 trial overview

Tumor

Unresectable locally advanced/metastatic non-squamous HER2 overexpressing NSCLC

Trial Identifier

NCT04686305

Phase

Ib

Stage

Metastatic, ≥1L

Regimen

T-DXd + durvalumab + (cisplatin/carboplatin/pemetrexed); T-DXd; T-DXd + volrustomig ± carboplatin; T-DXd + rilvegostomig ± carboplatin

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fam-trastuzumab deruxtecan-nxki in US only; trastuzumab deruxtecan in other regions of world.

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eVOLVE-Cervical trial overview

Tumor

High-risk locally advanced cervical cancer (FIGO 2018 Stage IIIA to IVA)

Trial Identifier

NCT06079671

Phase

III

Regimen

Volrustomig; placebo

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eVOLVE-01 trial overview

Tumor

NSCLC

Trial Identifier

NCT06448754

Phase

II

Regimen

Volrustomig (different doses) + chemotherapy; volrustomig + ramucirumab + chemotherapy

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eVOLVE-02 trial overview

Tumor

Advanced or metastatic tumors (Cervical, HNSCC, pleural mesothelioma, and ESCC)

Trial Identifier

NCT06535607

Phase

II

Regimen

Volrustomig monotherapy; volrustomig + chemotherapy

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eVOLVE-HNSCC trial overview

Tumor

Unresected locally advanced HNSCC not progressed on definitive concurrent chemoradiotherapy

Trial Identifier

NCT06129864

Phase

III

Regimen

Volrustomig; observational arm

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eVOLVE-Meso trial overview

Tumor

Advanced unresectable pleural mesothelioma

Trial Identifier

NCT06097728

Phase

III

Regimen

Volrustomig + carboplatin + pemetrexed; investigator's choice of standard care

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GEMINI-GC trial overview

Tumor

Locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma

Trial Identifier

NCT05702229

Phase

II

Regimen

Volrustomig + (XELOX or FOLFOX); rilvegostomig + (XELOX or FOLFOX); volrustomig + sonesitatug vedotin + (5-FU or capecitabine); sonesitatug vedotin + 5-FU or capecitabine ± rilvegostomig

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GEMINI-HPB trial overview

Tumor

Advanced hepatobiliary cancers (HCC, BTCs)

Trial Identifier

NCT05775159

Phase

II

Stage

Unresectable, advanced or metastatic

Regimen

In HCC - volrustomig monotherapy; volrustomig + bevacizumab or lenvatinib or rilvegostomig + bevacizumab; rilvegostomig + bevacizumab. In BTCs - volrustomig + gemcitabine and cisplatin; rilvegostomig + gemcitabine and cisplatin

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NCT04522323 trial overview

Tumor

Advanced RCC

Trial Identifier

NCT04522323

Phase

Ib

Stage

Advanced RCC

Regimen

Volrustomig + axitinib; volrustomig + lenvatinib

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NeoCOAST-2 trial overview

Tumor

Resectable stage IIA to IIIB NSCLC (EGFR/ALK wild-type)

Trial Identifier

NCT05061550

Phase

II

Stage

Resectable disease (IIA to IIIB)

Regimen

Oleclumab + durvalumab + PtCh; monalizumab + durvalumab + PtCh; volrustomig (dose exploration) + PtCh; Dato-DXd + durvalumab + single agent platinum; AZD0171 + durvalumab + PtCh; rilvegostomig + PtCh; Dato-DXd + rilvegostomig + single agent platinum

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TROPION-Lung04 trial overview

Tumor

Advanced/metastatic NSCLC without actionable genomic alterations and with/without previous treatment

Trial Identifier

NCT04612751

Phase

Ib

Stage

Advanced/metastatic NSCLC

Regimen

Dato-DXd + durvalumab ± carboplatin; Dato-DXd + rilvegostomig ± carboplatin; Dato-DXd + sabestomig

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TROPION-PanTumor03 trial overview

Tumor

Advanced solid tumors (endometrial, gastric, mCRPC, ovarian, colorectal, metastatic urothelial carcinoma, BTCs)

Trial Identifier

NCT05489211

Phase

II

Regimen

Dato-DXd; Dato-DXd + capecitabine or 5-FU; Dato-DXd + prednisone or prednisolone; Dato-DXd + carboplatin + bevacizumab followed by Dato-DXd + bevacizumab; Dato-DXd + bevacizumab + (5-FU + leucovorin or capecitabine); Dato-DXd+ 5-FU/leucovorin or capecitabine + bevacizumab; Dato-DXd + rilvegostomig or carboplatin/cisplatin

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Abbreviations

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  • 1L

    first line

  • ADA

    anti-drug antibody

  • AJCC

    American Joint Committee on Cancer

  • ALK

    anaplastic lymphoma kinase

  • BICR

    blinded independent central review

  • cCRT

    concurrent chemoradiation therapy

  • CD28

    cluster of differentiation 28

  • CD80

    cluster of differentiation 80

  • CD86

    cluster of differentiation 86

  • CNS

    central nervous system

  • COPD

    chronic obstructive pulmonary disease

  • CRC

    colorectal cancer

  • CT

    chemotherapy

  • CT

    computed tomography

  • CTLA-4

    cytotoxic T–lymphocyte-associated antigen 4

  • DoR

    duration of response

  • ECOG

    Eastern Cooperative Oncology Group

  • ECOG PS

    Eastern Cooperative Oncology Group Performance Score

  • EGFR

    epidermal growth factor receptor

  • FOLFIRI

    irinotecan, 5-FU, leucovorin

  • FOLFOX

    folinic acid (leucovorin), fluorouracil (5-FU), oxaliplatin

  • GHS

    global health status

  • HER2

    human epidermal growth factor receptor 2

  • HIV

    human immunodeficiency virus

  • HNSCC

    head and neck squamous cell carcinoma

  • IASLC

    International Association For The Study Of Lung Cancer

  • IV

    intravenous

  • mAb

    monoclonal antibody

  • mCRC

    metastatic CRC

  • MHC

    major histocompatibility complex

  • mNSCLC

    metastatic NSCLC

  • mRECIST

    modified Response Evaluation Criteria in Solid Tumors

  • MRI

    magnetic resonance imaging

  • MSS

    microsatellite-stable

  • NSCLC

    non-small cell lung cancer

  • ORR

    overall or objective response rate

  • OS

    overall survival

  • PD-1

    programmed cell death-1

  • PD-L1

    programmed cell death ligand-1

  • PD-L2

    programmed cell death ligand-2

  • PDC

    platinum doublet chemotherapy

  • PFS

    progression-free survival

  • PFS2

    time to second progression or death

  • PK

    pharmacokinetics

  • pMMR

    mismatch repair proficient

  • PS

    phosphatidylserine

  • PtCh

    platinum-based chemotherapy

  • Q*W

    every * weeks

  • QoL

    quality of life

  • R

    randomization

  • RCC

    renal cell carcinoma

  • RECIST v1.1

    Response Evaluation Criteria in Solid Tumors version 1.1

  • ROS1

    ROS proto-oncogene 1

  • RT

    radiotherapy

  • SCLC

    small cell lung cancer

  • SoC

    standard of care

  • TCR

    T-cell receptor

  • Teff

    effector T cells

  • TNM

    tumor node metastasis staging

  • Treg

    regulatory T cell

  • TROP2

    trophoblast cell-surface antigen 2

  • WHO

    World Health Organization

  • XELOX

    capecitabine, oxaliplatin

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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