A trial comparing the treatment of rilvegostomig with fluoropyrimidine and trastuzumab deruxtecan to the standard treatment in patients with HER2-positive gastric cancer.

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]

Trial duration

30 Jul 2025 → ongoing

Decision date (initial)

2025-06-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-512583-57-00

ClinicalTrials.gov

NCT06764875

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacoeconomic, Pharmacogenetic, Safety

To evaluate the efficacy of rilvegostomig in combination with fluoropyrimidine and T-DXd compared to trastuzumab, chemotherapy, and pembrolizumab, as measured by Progression-free Survival (PFS) per Blinded Independent Central Review and Overall Survival (OS).

Secondary objectives 6

1. To further evaluate the efficacy of rilvegostomig incombination with fluoropyrimidine and T-DXd compared totrastuzumab, chemotherapy, and pembrolizumab.
2. To evaluate the efficacy of rilvegostomig in combinationwith trastuzumab and chemotherapy compared totrastuzumab, chemotherapy, and pembrolizumab.
3. To evaluate the efficacy of of rilvegostomig in combination with fluoropyrimidine and T-DXd compared torilvegostomig in combination with trastuzumab andchemotherapy.
4. To evaluate the efficacy and assess the safety and tolerability of rilvegostomig in combination with fluoropyrimidine and T-DXd, and rilvegostomig in combination with trastuzumab and chemotherapy compared to trastuzumab, chemotherapy, and pembrolizumab.
5. To assess the PK of rilvegostomig, T-DXd, total anti-HER2antibody, DXd in serum, 5-FU and capecitabine in plasma.
6. To investigate the immunogenicity of rilvegostomig and T-DXd.

Conditions and MedDRA coding

HER2-positive locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000018-PIP17-78

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 9

1. HER2 positive for gastric cancer on a tumor biopsy.
2. PD-L1 combined positive score (CPS) ≥ 1.
3. Provision of tumor tissue sample from recent biopsy adequate for HER2 and PD-L1 testing.
4. Previously untreated, unresectable, locally advanced or metastatic gastric or GEJ adenocarcinoma.
5. WHO or Eastern Cooperative Oncology Group performance status of 0 or 1.
6. Have measurable target disease assessed by the Investigator based on RECISTv1.1.
7. Have adequate organ and bone marrow function within 14 days before randomization.
8. LVEF ≥ 55% within 28 days before randomization.
9. Adequate treatment washout period before randomization.

Exclusion criteria 20

1. Lack of physiological integrity of the upper gastrointestinal tract.
2. Chronic/active HBV or HCV infection unless controlled.
3. Clinically significant cardiac or psychological conditions.
4. Active or prior documented autoimmune or inflammatory disorders requiringchronic treatment with steroids or other immunosuppressive treatment.
5. History of (non-infectious) ILD/pneumonitis, has current ILD/pneumonitis, or wheresuspected ILD/pneumonitis cannot be ruled out by imaging at screening.
6. Lung-specific intercurrent clinically significant illnesses.
7. Any active non-infectious skin disease requiring systemic treatment.
8. A pleural effusion, ascites or pericardial effusion that requires drainage, peritonealshunt, or cell-free and concentrated ascites reinfusion therapy (CART).
9. History of any of the following: drug-induced severecutaneous adverse reaction.
10. Any concurrent anti-cancer treatment with the exception of receptor activator ofnuclear factor kappa-B ligand inhibitors.
11. Have had major surgical procedure recently (excluding placement of vascular access) or recent significant traumatic injury or an anticipated need for major surgery during the study.
12. Known dihydropyrimidine dehydrogenase enzyme deficiency.
13. Current or prior use of immunosuppressive medication within 14 days before study intervention.
14. Contraindication to pembrolizumab or trastuzumab, contraindications tofluoropyrimidine (5-FU and capecitabine) or platinum (cisplatin and oxaliplatin) treatment as per local label.
15. History of another primary malignancy except for malignancy treated with curativeintent with no known active disease within 3 years before the first dose of studyintervention and of low potential risk for recurrence.
16. Persistent toxicities caused by previous anti-cancer therapy.
17. Has spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring corticosteroid or anticonvulsant may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
18. Uncontrolled infection including tuberculosis and active hepatitis A infection.
19. Uncontrolled infection requiring intravenous (IV) antibiotics, anti-virals, or antifungals.
20. Recent receipt of live, attenuated vaccine.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Progression-free Survival (PFS) per RECIST v1.1
2. Overall Survival (OS)

Secondary endpoints 13

1. PFS based on RECIST v1.1.
2. Objective Response Rate (ORR) according to RECIST v1.1.
3. Duration of Response (DoR) according to RECIST v1.1.
4. Time to second progression or death.
5. Progression-free Survival (PFS) at 6 and 12 months (PFS6 and PFS12).
6. Overall Survival (OS) at 12 and 24 months (OS12 andOS24).
7. Occurrence of AEs, SAEs, AESIs.
8. Changes from baseline in laboratory parameters, vitalsigns, electrocardiogram data, and results ofechocardiogram/multiple gated acquisition.
9. Serum concentration of rilvegostomig, T-DXd, total anti-HER2 antibody, T-DXd, plasma concentration of 5-FU andcapecitabine.
10. Presence of anti-drug antibodies for rilvegostomig and T-DXd.
11. Time to increase in enteral feeding assistance and/or eating difficulties.
12. The proportion of time on study intervention with highside-effect bother.
13. The proportion of participants with stable or improvedphysical function while on treatment.

Investigational products

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

Test 7

Comparator 2

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

9 EU/EEA countries · 65 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 124 files

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

Application history

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