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Anti-CLDN18.2 ADC

CompoundSonesitatug vedotin (AZD0901)

Area under investigation

Advanced solid tumors, Gastric/GEJ cancer, Pancreatic cancer

Scientific PillarAntibody-Drug Conjugates

Target Overview

Claudin 18 is a trans-membrane protein and is an important component of the tight junction complexes that regulate cell-cell adhesion, cell permeability, and cell polarity. Alternative splicing of Claudin 18 transcripts results in 2 isoforms: CLDN18.1, which is expressed in the lung and CLDN18.2, which is restricted to the gastric epithelium. In normal tissues, CLDN18.2 expression is restricted to the gastric mucosa. In tumor tissues, CLDN18.2 is widely overexpressed in a variety of cancers such as gastric cancer (GC), gastroesophageal junction cancer (GEJC), pancreatic ductal adenocarcinoma (PDAC), and adenocarcinoma of esophagus.1

Compound Overview

Sonesitatug vedotin (AZD0901) is an ADC that consists of a humanized monoclonal antibody against CLDN18.2, conjugated to a potent microtubule inhibitor, monomethyl auristatin E (MMAE) via a protease cleavable linker.

Sonesitatug vedotin is designed to target and deliver the cytotoxic agent, MMAE, inside cancer cells that express CLDN18.2 and reduce systemic exposure to the cytotoxic payload compared to the way chemotherapy is commonly delivered.

The released MMAE payload also exerts bystander antitumor activity through cytotoxic activity in both the target cells and neighboring tumor cells, owing to its high cell membrane permeability.

Mechanism of Action

  • Mechanism of Action

References

1. Sahin U, Koslowski M, Dhaene K, et al. Clin Cancer Res. 2008;14(23):7624-7634.

Clinical trial information


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Area under investigation=true,Advanced solid tumors,Gastric/GEJ cancer,Pancreatic cancer

CLARITY-Gastric01 trial overview

Tumor

Advanced or metastatic gastric or GEJ adenocarcinoma expressing Claudin18.2, ≥2L

Trial Identifier

NCT06346392

Phase

III

Regimen

Sonesitatug vedotin (different doses); investigator's choice of chemotherapy

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CLARITY-Gastric02 trial overview

Tumor

1L advanced or metastatic GC, GEJ or esophageal adenocarcinoma expressing Claudin18.2

Trial Identifier

NCT07431281

Phase

III

Stage

1L advanced or metastatic GC, GEJ or esophageal adenocarcinoma expressing Claudin18.2

Regimen

Cohort 1: sonesitatug vedotin + rilvegostomig + capecitabine; sonesitatug vedotin + nivolumab + capecitabine; nivolumab + CAPOX or FOLFOX. Cohort 2: Sonesitatug vedotin + capecitabine; CAPOX or FOLFOX ± zolbetuximab

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CLARITY-PanTumor01 trial overview

Tumor

Claudin 18.2-positive advanced solid tumors (gastric/GEJ cancer, pancreatic adenocarcinoma, BTCs)

Trial Identifier

NCT06219941

Phase

II

Regimen

Sonesitatug vedotin; sonesitatug vedotin + chemotherapy

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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-PeriOp Gastric trial overview

Tumor

Locally advanced resectable GEJ adenocarcinoma

Trial Identifier

NCT07069712

Phase

II

Stage

Locally advanced resectable gastric, GEJ, or esophageal adenocarcinoma

Regimen

Sonesitatug vedotin + rilvegostomig and 5-FU or capecitabine; T-DXd + rilvegostomig and 5-FU or capecitabine; rilvegostomig + FLOT chemotherapy

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fam-trastuzumab deruxtecan-nxki in US only; trastuzumab deruxtecan in other regions of world. This study is sponsored by Daiichi Sankyo, Inc.

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Abbreviations

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  • 1L

    first line

  • 5-FU

    5-fluorouracil

  • ADA

    anti-drug antibodies

  • ADC

    antibody drug conjugate

  • CAPOX

    capecitabine and oxaliplatin

  • CLDN18.1

    Claudin 18.1 isoform

  • CLDN18.2

    Claudin 18.2

  • CPS

    combined positive score

  • CNS

    central nervous system

  • CTCAE

    Common Terminology Criteria for Adverse Events

  • DoR

    duration of response

  • DNA

    deoxyribonucleic acid

  • DPD

    dihydropyrimidine dehydrogenase

  • ECOG

    eastern cooperative oncology group

  • EAC

    esophageal adenocarcinoma

  • FLOT

    docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil

  • FOLFOX

    5-fluorouracil, leucovorin, and oxaliplatin

  • GC

    gastric cancer

  • GEJ

    gastroesophageal junction

  • GEJC

    gastroesophageal junction cancer

  • GI

    gastrointestional

  • HBV

    Hepatitis B Virus

  • HER2

    human epidermal growth factor receptor 2

  • HIV

    human immunodeficiency virus

  • ICF

    informed consent form

  • ICI

    immune checkpoint inhibitor

  • IHC

    immunohistochemistry

  • MMAE

    monomethyl auristatin E

  • ORR

    objective response rate

  • OS

    overall survival

  • PD-L1

    programmed death-ligand 1

  • PFS

    progression-free survival

  • PK

    pharmacokinetic

  • PO

    per oral (by mouth)

  • PROs

    patient-reported outcomes

  • RECIST

    Response Evaluation Criteria in Solid Tumors

  • T-DXd

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

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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