Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in Participants With Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma Expressing Claudin18.2

NCT07431281
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Phase
Phase 3
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Recruitment status
Recruiting
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Participants
2,130
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Lead sponsor
AstraZeneca
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Start date
2026-02-03
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Number of sites
286
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Summary
The purpose of this study is to evaluate the efficacy and safety of sonesitatug vedotin in combination with capecitabine with or without rilvegostomig in first-line (1L) Claudin18.2 (CLDN18.2)-positive, human epidermal growth factor receptor 2 (HER2)-negative, gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.
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Short title
Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in Participants With Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma Expressing Claudin18.2
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Official title
A Phase III, Multicentre, Randomised Controlled Study of Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in First-Line Claudin18.2-Positive, HER2-Negative, Advanced/Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (CLARITY-Gastric 02)
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2031-10-27
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First posted
2026-02-24
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Registry last updated
2026-07-01
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Primary completion date
2029-08-16
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Start date
2026-02-03
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Participants
2,130
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Participant count basis
Estimated
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Planned participants
2,130
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Protocol amendments
0
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Number of sites
286
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
AstraZeneca
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Source registry
ClinicalTrials.gov
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Registry ID
NCT07431281
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ClinicalTrials.gov ID
NCT07431281
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Single masking
Masking description
This is an open-label study; however, it will be conducted 'sponsor blind' and the specific treatment to be taken by a participant will be assigned using an IRT/RTSM. To maintain the integrity of the study, sponsor access to treatment records will be restricted, unless a positive result is observed at an interim analysis and access is required as per protocol-defined procedures
Masked roles
Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Progression Free Survival (PFS) (Cohort 1 and Cohort 2)

    Timeframe: Up to approximately 5 years

    PFS is defined as time from randomisation until progression per RECIST 1.1, or death due to any cause, whichever occurs first.

  2. Overall Survival (OS) (Cohort 1)

    Timeframe: Up to approximately 5 years

    OS is defined as the time from randomisation until the date of death due to any cause.

  1. Overall Survival (OS) (Cohort 2)

    Timeframe: Up to approximately 5 years

    OS is defined as the time from randomisation until the date of death due to any cause.

  2. Overall Survival (OS) (Cohort 1)

    Timeframe: Up to approximately 5 years

    OS is defined as time from randomisation until date of death due to any cause. Arm B versus C.

  3. Progression Free Survival (PFS) (Cohort 1)

    Timeframe: Up to approximately 5 years

    PFS is defined as time from randomisation until progression per RECIST 1.1 or death due to any cause, whichever occurs first. Arms B versus C.

  4. Objective Response Rate (ORR) (Cohort 1 and Cohort 2)

    Timeframe: Up to approximately 5 years

    ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, per RECIST 1.1.

  5. Duration of Response (DoR) (Cohort 1 and Cohort 2)

    Timeframe: Up to approximately 5 years

    DoR (per RECIST 1.1) is derived for confirmed objective responses (CR or PR) only and is defined as the time from the date of first documented response (which is subsequently confirmed) until date of documented progression or death in the absence of disease progression (ie, date of PFS event - date of first response + 1).

  6. Pharmacokinetics of sonesitatug vedotin (Cohort 1 and Cohort 2)

    Timeframe: Up to approximately 5 years

    Pharmacokinetic parameters of sonesitatug vedotin (peak plasma concentration (Cmax))

  7. Pharmacokinetics of sonesitatug vedotin (Cohort 1 and Cohort 2)

    Timeframe: Up to approximately 5 years

    Pharmacokinetic parameters of sonesitatug vedotin (trough plasma concentration (Cmin))

  8. Immunogenicity of sonesitatug vedotin (Cohort 1 and Cohort 2)

    Timeframe: Up to approximately 5 years

    Presence of ADAs for sonesitatug vedotin in serum (confirmatory results: positive or negative, titres).

  9. Pharmacokinetics of rilvegostomig (Cohort 1)

    Timeframe: Up to approximately 5 years

    Pharmacokinetic parameters of rilvegostomig (peak plasma concentration (Cmax))

  10. Pharmacokinetics of rilvegostomig (Cohort 1)

    Timeframe: Up to approximately 5 years

    Pharmacokinetic parameters of rilvegostomig (trough plasma concentration (Cmin))

  11. Immunogenicity of rilvegostomig (Cohort 1)

    Timeframe: Up to approximately 5 years

    Presence of ADAs for rilvegostomig in serum (confirmatory results: positive or negative, titres).

  12. Safety and tolerability (Cohort 1 and Cohort 2)

    Timeframe: Up to approximately 5 years

    Safety and tolerability as evaluated in terms of incidence of AEs and SAEs

Sources for outcomes
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Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • Capable of giving signed informed consent

  • Participant must be 18 years or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent.

  • Previously untreated histologically documented unresectable, locally advanced, or metastatic gastric, GEJ, or distal esophagus (distal third of the esophagus) adenocarcinoma

  • Positive CLDN18.2 expression, as determined prospectively by central IHC testing

  • Confirmed PD-L1 CPS status by central IHC testing and ICI eligibility per investigator judgement is required to determine cohort eligibility as described below:

    1. Cohort 1: PD-L1 positive as determined by central IHC testing and the participant is deemed ICI eligible per investigator judgement.
    2. Cohort 2: PD-L1 negative as determined by central IHC testing OR the participant is ICI ineligible

  • ECOG performance status of 0 or 1 with no deterioration to > 1 over the previous 2 weeks prior to baseline at screening and prior to randomisation.

  • Minimum life expectancy of ≥ 12 weeks.

  • At least one lesion (measurable and/or non-measurable) that can be accurately assessed by the investigator based on RECIST 1.1.

  • Adequate organ and bone marrow function as specified in the protocol

  • Body weight ≥ 35 kg.

  • Sex and contraceptive requirements

  • Known HER2-positive status
  • Significant or unstable gastric bleeding and/or untreated gastric ulcers.
  • Active or history of autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment or assessed by investigator as not appropriate to participate due to undue risk are excluded.
  • CNS pathology
  • Clinically significant pleural effusions or ascites and/or pleural effusions or ascites that require drainage, peritoneal shunt, or indwelling catheter/drain.
  • Require parenteral nutrition support due to gastric or gastrointestinal obstruction.
  • Peripheral neuropathy, sensory or motor, ≥ CTCAE Grade 2 at screening.
  • Persistent toxicities caused by previous anticancer therapy excluding alopecia, not yet improved to Grade ≤ 1 or baseline.
  • Cardiac abnormalities as outlined in the protocol
  • Uncontrolled diabetes or diabetic neuropathy within 3 months prior to randomisation.
  • Infectious disease including active hepatitis A infection; uncontrolled hepatitis B and/or chronic or active hepatitis B with HBV DNA ≥ 100 IU/mL; Known chronic, active, or uncontrolled hepatitis C; HIV infection that is not well controlled
  • Known partial or total DPD enzyme deficiency
Sources for eligibility
clinicaltrials.gov

  • Research SiteMobile, United StatesNot yet recruiting
  • Research SiteAnchorage, United StatesNot yet recruiting
  • Research SitePhoenix, United StatesNot yet recruiting
  • Research SiteSpringdale, United StatesNot yet recruiting
  • Research SiteDuarte, United StatesNot yet recruiting
  • Research SiteFullerton, United StatesNot yet recruiting
  • Research SiteLa Jolla, United StatesNot yet recruiting
  • Research SiteLos Alamitos, United StatesNot yet recruiting
  • Research SiteOrange, United StatesNot yet recruiting
  • Research SiteWalnut Creek, United StatesNot yet recruiting
  • Research SiteDenver, United StatesNot yet recruiting
  • Research SiteLone Tree, United StatesNot yet recruiting
  • Research SiteNew Haven, United StatesWithdrawn
  • Research SiteNewark, United StatesNot yet recruiting
  • Research SiteWashington D.C., United StatesWithdrawn
  • Research SiteFort Myers, United StatesWithdrawn
  • Research SiteJacksonville, United StatesNot yet recruiting
  • Research SiteOrlando, United StatesNot yet recruiting
  • Research SiteSt. Petersburg, United StatesWithdrawn
  • Research SiteWest Palm Beach, United StatesWithdrawn
  • Research SiteAtlanta, United StatesNot yet recruiting
  • Research SiteAtlanta, United StatesNot yet recruiting
  • Research SiteAtlanta, United StatesWithdrawn
  • Research SiteMacon, United StatesNot yet recruiting
  • Research SiteNewnan, United StatesNot yet recruiting

And 261 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2024-519787-40-00
Sources for references
clinicaltrials.gov

Related records

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Lead sponsors (1)

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Targets (3)