Print

Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Cohort 1 (3-arm design) will evaluate sonesitatug vedotin in combination with rilvegostomig and capecitabine (Arm A) or sonesitatug vedotin in combination with nivolumab and capecitabine (Arm B), versus SoC nivolumab plus capecitabine plus oxaliplatin (CAPOX) or folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) (Arm C) in PD-L1 positive participants. Participants will be randomized 1:1:1 to Arms A, B, or C. Cohort 2 (2-arm design) will evaluate sonesitatug vedotin in combination with capecitabine (Arm D) versus SoC (Arm E) in participants who are PD-L1 negative or ICI-ineligible. Participants will be randomised 1:1. SoC is CAPOX or FOLFOX alone or in combination with zolbetuximab.
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)
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

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A 		Sonesitatug vedotin + Rilvegostomig + Capecitabine
  • Drug: Sonesitatug vedotin
    Intravenous
    Other names:
    • AZD0901
  • Drug: Rilvegostomig
    Intravenous
    Other names:
    • AZD2936
  • Drug: Capecitabine
    Oral
Experimental
Arm B 		Sonesitatug vedotin + Nivolumab + Capecitabine
  • Drug: Sonesitatug vedotin
    Intravenous
    Other names:
    • AZD0901
  • Drug: Nivolumab
    Intravenous
  • Drug: Capecitabine
    Oral
Active Comparator
Arm C 		Nivolumab + CAPOX OR Nivolumab + FOLFOX - nivolumab, capecitabine, oxaliplatin - nivolumab, 5-Fluorouracil, leucovorin, oxaliplatin
  • Drug: Nivolumab
    Intravenous
  • Drug: Capecitabine
    Oral
  • Drug: 5-Fluorouracil
    Intravenous
  • Drug: Oxaliplatin
    Intravenous
  • Drug: Leucovorin
    Intravenous
Experimental
Arm D 		Sonesitatug vedotin + Capecitabine
  • Drug: Sonesitatug vedotin
    Intravenous
    Other names:
    • AZD0901
  • Drug: Capecitabine
    Oral
Active Comparator
Arm E 		Zolbetuximab + CAPOX or Zolbetuximab + FOLFOX: - zolbetuximab, capecitabine, oxaliplatin - zolbetuximab, 5-Fluorouracil, leucovorin, oxaliplatin CAPOX or FOLFOX: - oxaliplatin, capecitabine, - 5-Fluorouracil, leucovorin, oxaliplatin
  • Drug: Capecitabine
    Oral
  • Drug: 5-Fluorouracil
    Intravenous
  • Drug: Oxaliplatin
    Intravenous
  • Drug: Zolbetuximab
    Intravenous
  • Drug: Leucovorin
    Intravenous

Recruiting Locations

Research Site
Grand Rapids, Michigan 49503

Research Site
St Louis, Missouri 63110

Research Site
East Brunswick, New Jersey 08816

Research Site
Nashville, Tennessee 37203

More Details

Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

Detailed Description

The purpose of this Phase III study is to evaluate the efficacy and safety of sonesitatug vedotin in combination with capecitabine with or without rilvegostomig in 1L CLDN18.2-positive, HER2-negative gastric, GEJ, and esophageal adenocarcinoma, and the clinical performance of the investigation in vitro diagnostics (IVDs). The study will include 2 cohorts to provide a treatment option for all participants that are HER2-negative and CLDN18.2-positive. Cohort 1 will evaluate sonesitatug vedotin in combination with rilvegostomig with capecitabine in participants who are CLDN18.2-positive and programmed death-ligand 1 (PD-L1) positive. Cohort 2 will evaluate sonesitatug vedotin in combination with capecitabine in participants who are CLDN18.2-positive and PD-L1 negative or immune checkpoint inhibitor (ICI) ineligible.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.