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

AstraZeneca

Status and phase

Enrolling

Phase 3

Conditions

Esophageal Cancer

Gastric Cancer

Gastroesophageal Junction Adenocarcinoma

Treatments

Drug: Sonesitatug vedotin

Drug: Nivolumab

Drug: Rilvegostomig

Drug: Leucovorin

Drug: Zolbetuximab

Drug: Oxaliplatin

Drug: Capecitabine

Drug: 5-Fluorouracil

Study type

Interventional

Funder types

Industry

Identifiers

NCT07431281

2024-519787-40-00 (Registry Identifier)

D9803C00001

Details and patient eligibility

About

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.

Full 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.

Enrollment

2,130 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Single Blind

2,130 participants in 5 patient groups

Arm A

Experimental group

Description:

Sonesitatug vedotin + Rilvegostomig + Capecitabine

Treatment:

Drug: Capecitabine

Drug: Rilvegostomig

Drug: Sonesitatug vedotin

Arm B

Experimental group

Description:

Sonesitatug vedotin + Nivolumab + Capecitabine

Treatment:

Drug: Capecitabine

Drug: Nivolumab

Drug: Sonesitatug vedotin

Arm C

Active Comparator group

Description:

Nivolumab + CAPOX OR Nivolumab + FOLFOX * nivolumab, capecitabine, oxaliplatin * nivolumab, 5-Fluorouracil, leucovorin, oxaliplatin

Treatment:

Drug: 5-Fluorouracil

Drug: Capecitabine

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Nivolumab

Arm D

Experimental group

Description:

Sonesitatug vedotin + Capecitabine

Treatment:

Drug: Capecitabine

Drug: Sonesitatug vedotin

Arm E

Active Comparator group

Description:

Zolbetuximab + CAPOX or Zolbetuximab + FOLFOX: * zolbetuximab, capecitabine, oxaliplatin * zolbetuximab, 5-Fluorouracil, leucovorin, oxaliplatin CAPOX or FOLFOX: * oxaliplatin, capecitabine, * 5-Fluorouracil, leucovorin, oxaliplatin

Treatment:

Drug: 5-Fluorouracil

Drug: Capecitabine

Drug: Oxaliplatin

Drug: Zolbetuximab

Drug: Leucovorin