A trial to learn how well sonesitatug vedotin and capecitabine with or without rilvegostomig work and how safe they are in adults with cancers of the stomach and esophagus.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-06-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacoeconomic, Pharmacogenomic, Efficacy, Pharmacokinetic

Cohort 1: To demonstrate the superiority of sonesitatug vedotin + rilvegostomig + capecitabine relative to SoC by assessment of PFS and OS.
Cohort 2: To demonstrate the superiority of sonesitatug vedotin + capecitabine relative to SoC by assessment of PFS

Secondary objectives 13

1. To demonstrate the superiority of sonesitatug vedotin + capecitabine relative to SoC by assessment of OS (cohort 2)
2. To demonstrate the effectiveness of sonesitatug vedotin + nivolumab + capecitabine relative to SoC by assessment of PFS (cohort 1)
3. To demonstrate the effectiveness of sonesitatug vedotin + nivolumab + capecitabine relative to SoC by assessment of OS (cohort 1)
4. To demonstrate the effectiveness of sonesitatug vedotin + rilvegostomig + capecitabine relative to SoC by assessment of ORR (cohort 1)
5. To demonstrate the effectiveness of sonesitatug vedotin + capecitabine relative to SoC by assessment of ORR (cohort 2)
6. To demonstrate the effectiveness of sonesitatug vedotin + rilvegostomig + capecitabine relative to SoC by assessment of DoR (cohort 1)
7. To demonstrate the effectiveness of sonesitatug vedotin + nivolumab + capecitabine relative to SoC by assessment of ORR and DoR (cohort 1).
8. To demonstrate the effectiveness of sonesitatug vedotin + capecitabine relative to SoC by assessment of DoR (cohort 2)
9. To assess the PK and immunogenicity of sonesitatug vedotin (cohort 1 and 2)
10. To assess the PK and immunogenicity of rilvegostomig (cohort 1)
11. To assess the safety and tolerability of sonesitatug vedotin + rilvegostomig + capecitabine as compared with SoC (cohort 1)
12. To assess the safety and tolerability of sonesitatug vedotin + nivolumab + capecitabine as compared with SoC (cohort 1)
13. To assess the safety and tolerability of sonesitatug vedotin + capecitabine as compared with SoC (cohort 2)

Conditions and MedDRA coding

Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Esophageal Cancer Expressing Claudin18.2

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Capable of giving signed informed consent
2. 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.
3. Previously untreated histologically documented unresectable, locally advanced, or metastatic gastric, GEJ, or distal esophagus (distal third of the esophagus) adenocarcinoma
4. Positive CLDN18.2 expression
5. Confirmed PD-L1 CPS status by central IHC testing and ICI eligibility per investigator judgement is required to determine cohort eligibility: a) Cohort 1: PD-L1 CPS ≥ 1 as determined by central IHC testing and the participant is deemed ICI eligible per investigator judgement. b) Cohort 2: PD-L1 CPS < 1 as determined by central IHC testing OR the participant is ICI ineligible
6. 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.
7. Minimum life expectancy of ≥ 12 weeks.
8. At least one lesion (measurable and/or non-measurable) that can be accurately assessed by the investigator based on B6RECIST 1.1.
9. Adequate organ and bone marrow function as specified in the protocol
10. Body weight ≥ 35 kg.
11. Sex and contraceptive requirements

Exclusion criteria 12

1. Known HER2-positive status
2. Significant or unstable gastric bleeding and/or untreated gastric ulcers.
3. 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.
4. CNS pathology
5. Clinically significant pleural effusions or ascites and/or pleural effusions or ascites that require drainage, peritoneal shunt, or indwelling catheter/drain.
6. Require parenteral nutrition support due to gastric or gastrointestinal obstruction.
7. Peripheral neuropathy, sensory or motor, ≥ CTCAE Grade 2 at screening.
8. Persistent toxicities caused by previous anticancer therapy excluding alopecia, not yet improved to Grade ≤ 1 or baseline.
9. Cardiac abnormalities as outlined in the protocol
10. Uncontrolled diabetes or diabetic neuropathy within 3 months prior to randomisation.
11. 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
12. Known partial or total DPD enzyme deficiency

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Progression Free Survival (PFS) per RECIST 1.1 (Cohort 1 and Cohort 2)
2. Overall Survival (OS) (Cohort 1 )

Secondary endpoints 10

1. Overall Survival (OS) (Cohort 2)
2. Overall Survival (OS) (Cohort 1 Arm B and C)
3. Progression Free Survival (PFS) per RECIST 1.1 (Cohort 1 Arm B and C)
4. Objective Response Rate (ORR) per RECIST 1.1 (Cohort 1 and Cohort 2)
5. Duration of Response (DoR) per RECIST 1.1 (Cohort 1 and Cohort 2)
6. Concentration of sonesitatug vedotin, total antibody and MMAE in serum and PK parameters (Cohort 1 and Cohort 2)
7. Concentration of rilvegostomig in serum and PK parameters (Cohort 1)
8. Presence of ADAs for sonesitatug vedotin (Cohort 1 and Cohort 2)
9. Presence of ADAs for rilvegostomig (Cohort 1)
10. Incidence of AEs and SAEs, changes from baseline in vital signs, clinical laboratory results, and ECGs (Cohort 1 and Cohort 2)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 4

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

8 EU/EEA countries · 56 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 80 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications