Recruiting NCT07431281

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

Phase III Interventional Gastric Cancer Gastroesophageal Junction Adenocarcinoma Esophageal Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Sonesitatug vedotin, Rilvegostomig, Nivolumab, Capecitabine.
Who it may be relevant to: Registry conditions: Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Esophageal Cancer. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, Austria, Belgium, Brazil +17
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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)

Overview

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.

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.

Interventions

Drug Sonesitatug vedotin
Intravenous
Drug Rilvegostomig
Intravenous
Drug Nivolumab
Intravenous
Drug Capecitabine
Oral
Drug 5-Fluorouracil
Intravenous
Drug Oxaliplatin
Intravenous
Drug Zolbetuximab
Intravenous
Drug Leucovorin
Intravenous

Primary outcome measures

Progression Free Survival (PFS) (Cohort 1 and Cohort 2) [Time frame: Up to approximately 5 years]
Overall Survival (OS) (Cohort 1) [Time frame: Up to approximately 5 years]

Secondary outcome measures (12)

Overall Survival (OS) (Cohort 2) [Time frame: Up to approximately 5 years]
Overall Survival (OS) (Cohort 1) [Time frame: Up to approximately 5 years]
Progression Free Survival (PFS) (Cohort 1) [Time frame: Up to approximately 5 years]
Objective Response Rate (ORR) (Cohort 1 and Cohort 2) [Time frame: Up to approximately 5 years]
Duration of Response (DoR) (Cohort 1 and Cohort 2) [Time frame: Up to approximately 5 years]
Pharmacokinetics of sonesitatug vedotin (Cohort 1 and Cohort 2) [Time frame: Up to approximately 5 years]
Pharmacokinetics of sonesitatug vedotin (Cohort 1 and Cohort 2) [Time frame: Up to approximately 5 years]
Immunogenicity of sonesitatug vedotin (Cohort 1 and Cohort 2) [Time frame: Up to approximately 5 years]
Pharmacokinetics of rilvegostomig (Cohort 1) [Time frame: Up to approximately 5 years]
Pharmacokinetics of rilvegostomig (Cohort 1) [Time frame: Up to approximately 5 years]
Immunogenicity of rilvegostomig (Cohort 1) [Time frame: Up to approximately 5 years]
Safety and tolerability (Cohort 1 and Cohort 2) [Time frame: Up to approximately 5 years]

Eligibility criteria

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:

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Single blind
Primary purpose: Treatment