NCT06764875

Brief Summary

This is a Phase Ⅲ, randomized, open-label, Sponsor-blinded, 3-arm, global, multicenter study assessing the efficacy and safety of rilvegostomig in combination with fluoropyrimidine and T-DXd (Arm A) compared to trastuzumab, chemotherapy, and pembrolizumab (Arm B) in HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma participants whose tumors express PD L1 CPS ≥ 1. Rilvegostomig in combination with trastuzumab and chemotherapy will be evaluated in a separate arm (Arm C) to assess the contribution of each component in the experimental arm.

Trial Health

88
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
840

participants targeted

Target at P75+ for phase_3

Timeline
56mo left

Started Mar 2025

Longer than P75 for phase_3

Geographic Reach
27 countries

282 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress21%
Mar 2025Dec 2030

First Submitted

Initial submission to the registry

December 12, 2024

Completed
28 days until next milestone

First Posted

Study publicly available on registry

January 9, 2025

Completed
2 months until next milestone

Study Start

First participant enrolled

March 1, 2025

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 27, 2029

Expected
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 9, 2030

Last Updated

April 9, 2026

Status Verified

April 1, 2026

Enrollment Period

4.2 years

First QC Date

December 12, 2024

Last Update Submit

April 8, 2026

Conditions

Outcome Measures

Primary Outcomes (2)

  • Progression free survival (PFS)

    PFS is defined as time from randomization until progression per RECIST v1.1, or death due to any cause.

    Up to approximately 6 years

  • Overall Survival (OS)

    OS is defined as time from randomization until the date of death due to any cause.

    Up to approximately 6 years

Secondary Outcomes (13)

  • Objective Response Rate (ORR)

    Up to approximately 6 years

  • Duration of Response (DoR)

    Up to approximately 6 years

  • Proportion of all randomized participants alive and progression-free at 6 months (PFS6)

    Up to 6 months

  • Proportion of all randomized participants alive and progression-free at 12 months (PFS12)

    Up to 12 months

  • Time to second progression or death (PFS2)

    Up to approximately 6 years

  • +8 more secondary outcomes

Study Arms (3)

Arm A

EXPERIMENTAL

T-DXd + Rilvegostomig + Fluoropyrimidine (Capecitabine OR 5-FU)

Drug: RilvegostomigDrug: Trastuzumab deruxtecanDrug: 5-fluorouracilDrug: Capecitabine

Arm B

ACTIVE COMPARATOR

Pembrolizumab + Trastuzumab + FP (5-FU plus cisplatin) or CAPOX (capecitabine plus oxaliplatin)

Drug: TrastuzumabDrug: PembrolizumabDrug: 5-fluorouracilDrug: CapecitabineDrug: CisplatinDrug: Oxaliplatin

Arm C

ACTIVE COMPARATOR

Rilvegostomig + Trastuzumab + FP (5-FU plus cisplatin) or CAPOX (capecitabine plus oxaliplatin)

Drug: RilvegostomigDrug: TrastuzumabDrug: 5-fluorouracilDrug: CapecitabineDrug: CisplatinDrug: Oxaliplatin

Interventions

Q3W, intravenous infusion

Also known as: AZD2936
Arm AArm C

Q3W, intravenous infusion

Also known as: T-DXd, DS-8201
Arm A

Q3W, intravenous infusion

Arm BArm C

Q3W, intravenous infusion

Arm B

Q3W, intravenous infusion

Also known as: 5-FU
Arm AArm BArm C

BID, oral administration

Arm AArm BArm C

Q3W, intravenous infusion

Arm BArm C

Q3W, intravenous infusion

Arm BArm C

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • HER2 positive for gastric cancer on a tumor biopsy.
  • PD-L1 combined positive score (CPS) ≥ 1.
  • Provision of tumor tissue sample from recent biopsy adequate for HER2 and PD-L1 testing.
  • Previously untreated, unresectable, locally advanced or metastatic gastric or GEJ adenocarcinoma.
  • WHO or Eastern Cooperative Oncology Group performance status of 0 or 1.
  • Have measurable target disease assessed by the Investigator based on RECIST v1.1.
  • Have adequate organ and bone marrow function.
  • LVEF ≥ 50% within 28 days before randomization.
  • Adequate treatment washout period before randomization.

You may not qualify if:

  • Lack of physiological integrity of the upper gastrointestinal tract.
  • Known dihydropyrimidine dehydrogenase enzyme deficiency.
  • Contraindication to pembrolizumab or trastuzumab, contraindications to fluoropyrimidine (5-FU and capecitabine) or platinum (cisplatin and oxaliplatin) treatment as per local label.
  • History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence.
  • Persistent toxicities caused by previous anti-cancer therapy.
  • 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.
  • Uncontrolled infection including tuberculosis and active hepatitis A infection.
  • Uncontrolled infection requiring intravenous (IV) antibiotics, anti-virals, or antifungals.
  • Recent receipt of live, attenuated vaccine.
  • Chronic/active HBV or HCV infection unless controlled.
  • Clinically significant cardiac or psychological conditions.
  • Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
  • History of (non-infectious) ILD/pneumonitis, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
  • Lung-specific intercurrent clinically significant illnesses.
  • Any active non-infectious skin disease requiring systemic treatment.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (286)

Research Site

Anchorage, Alaska, 99508, United States

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Phoenix, Arizona, 85054, United States

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Duarte, California, 91010, United States

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La Jolla, California, 92037, United States

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Los Alamitos, California, 90720, United States

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Los Angeles, California, 90089, United States

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Santa Monica, California, 90404, United States

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Solvang, California, 93463, United States

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Upland, California, 91786, United States

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Walnut Creek, California, 94598, United States

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Aurora, Colorado, 80045, United States

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Newark, Delaware, 19713, United States

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Jacksonville, Florida, 32207, United States

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Jacksonville, Florida, 32224, United States

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Orlando, Florida, 32806, United States

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Marietta, Georgia, 30060, United States

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Chicago, Illinois, 60612, United States

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Chicago, Illinois, 60637, United States

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Evanston, Illinois, 60201, United States

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Hinsdale, Illinois, 60521, United States

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Niles, Illinois, 60714, United States

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Dyer, Indiana, 46311, United States

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Louisville, Kentucky, 40217, United States

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Silver Spring, Maryland, 20904, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02118, United States

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Detroit, Michigan, 48202, United States

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Grand Rapids, Michigan, 49503, United States

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Burnsville, Minnesota, 55337, United States

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Kansas City, Missouri, 64111, United States

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St Louis, Missouri, 63108, United States

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Omaha, Nebraska, 68198-5885, United States

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Reno, Nevada, 89502, United States

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Summit, New Jersey, 07901, United States

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Santa Fe, New Mexico, 87505, United States

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New Hyde Park, New York, 11042, United States

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New York, New York, 10021, United States

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Cincinnati, Ohio, 45220, United States

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Columbus, Ohio, 43210, United States

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Philadelphia, Pennsylvania, 19104, United States

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Knoxville, Tennessee, 37909, United States

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Nashville, Tennessee, 37232, United States

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Dallas, Texas, 75246, United States

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Webster, Texas, 77598, United States

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Charlottesville, Virginia, 22908, United States

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Fairfax, Virginia, 22031, United States

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Fairfax, Virginia, 22031, United States

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Richmond, Virginia, 23235, United States

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Charleston, West Virginia, 25304, United States

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Madison, Wisconsin, 53792, United States

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Buenos Aires, 1264, Argentina

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Ciudad Autónoma Buenos Aires, C1430EFA, Argentina

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Ciudad de Buenos Aires, 1280, Argentina

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Rosario, 2123, Argentina

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Rosario, S2000DEJ, Argentina

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Viedma, R8500ACE, Argentina

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Darlinghurst, 2010, Australia

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Heidelberg, 3084, Australia

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Murdoch, 6150, Australia

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Westmead, 2145, Australia

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Linz, 4010, Austria

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Salzburg, 5020, Austria

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Vienna, 1090, Austria

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Wiener Neustadt, 2700, Austria

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Edegem, 2650, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Barretos, 14784-057, Brazil

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Brasília, 71681-603, Brazil

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Campo Grande, 79020-180, Brazil

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Natal, 59075-740, Brazil

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Porto Alegre, 91350-200, Brazil

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Recife, 50040-000, Brazil

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Salvador, 40170-110, Brazil

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São Paulo, 05652-9000, Brazil

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Vitória, 29043-272, Brazil

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Calgary, Alberta, T2N 5G2, Canada

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Edmonton, Alberta, T6G 1Z2, Canada

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Winnipeg, Manitoba, R3E 0V9, Canada

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Barrie, Ontario, L4M 6M2, Canada

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Brampton, Ontario, L6R 3J9, Canada

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Hamilton, Ontario, L8V 5C2, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Chicoutimi, Quebec, G7H 5H6, Canada

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Montreal, Quebec, H3A 1A1, Canada

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Port Montt, 5480000, Chile

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Rancagua, 2852424, Chile

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Santiago, 7500653, Chile

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Santiago, 7620002, Chile

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Santiago, 8241479, Chile

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Temuco, 4810218, Chile

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Viña del Mar, 2520598, Chile

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Anyang, 455000, China

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Beijing, 100050, China

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Beijing, CN-100730, China

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Bengbu, 233004, China

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Changchun, 130021, China

SUSPENDED

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Changsha, 410013, China

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Chengdu, 610041, China

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Fuzhou, 350001, China

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Fuzhou, 350014, China

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Guangzhou, 510060, China

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Guangzhou, 510655, China

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Guangzhou, 510700, China

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Hangzhou, 310016, China

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Harbin, 150081, China

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Hefei, 230022, China

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Hefei, 230031, China

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Jinan, 250021, China

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Kunming, 650118, China

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Lanzhou, 730000, China

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Linfen, 041099, China

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Linyi, 276001, China

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Nanchang, 330008, China

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Nanjing, 210009, China

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Nanjing, 210029, China

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Shandong, China

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Shanghai, 200025, China

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Shanghai, 200032, China

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Shanghai, 201114, China

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Shenyang, 110004, China

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Shenyang, 110042, China

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Shijiazhuang, 050000, China

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Tianjin, 300060, China

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Wenzhou, 325000, China

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Wuhan, 430030, China

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Xi'an, 710061, China

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Xi'an, 710068, China

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Xining, 810001, China

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Yinchuan, 750004, China

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Zhengzhou, 450008, China

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Bordeaux, 33076, France

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Caen, 14000, France

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Clermont-Ferrand, 63003, France

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Dijon, 21079, France

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Lyon, 69373, France

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Marseille, 13273, France

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Poitiers, 86021, France

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Rennes, 35000, France

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Toulouse, 31059, France

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Villejuif, 94805, France

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Augsburg, 86156, Germany

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Bad Saarow, 15526, Germany

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Berlin, 10249, Germany

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Berlin, 10707, Germany

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Berlin, 13353, Germany

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Braunschweig, 38114, Germany

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Chemnitz, 9116, Germany

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Düsseldorf, 40225, Germany

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Essen, 45122, Germany

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Frankfurt, 60488, Germany

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Göttingen, 37075, Germany

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Hamburg, 20246, Germany

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Leipzig, 04103, Germany

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Ludwigshafen, 67063, Germany

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Mannheim, 68167, Germany

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Ulm, 89081, Germany

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Hong Kong, 150001, Hong Kong

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Hong Kong, 999077, Hong Kong

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Hong Kong, Hong Kong

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Hong Kong, Hong Kong

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Shatin, 00000, Hong Kong

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Budapest, 1083, Hungary

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Budapest, 1122, Hungary

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Budapest, 1145, Hungary

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Gyöngyös, 3200, Hungary

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Győr, 9024, Hungary

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Gyula, 5700, Hungary

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Zalaegerszeg, 8900, Hungary

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Ansārinagar, 110 029, India

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Bangalore, 560027, India

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Delhi, 110029, India

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Delhi, 110085, India

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Hyderabad, 500034, India

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Kolkata, 700094, India

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Mumbai, 400012, India

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Varanasi, 221005, India

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Cagliari, 09124, Italy

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Florence, 50134, Italy

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Milan, 20162, Italy

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Naples, 80131, Italy

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Padova, 35128, Italy

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Rozzano, 20089, Italy

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Torino, 10126, Italy

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Tricase, 73039, Italy

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Akashi-shi, 673-8558, Japan

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Bunkyō City, 113-8677, Japan

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Chūōku, 104-0045, Japan

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Fukuoka, 811-1395, Japan

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Fukuoka, 812-8582, Japan

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Hidaka-shi, 350-1298, Japan

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Hirakata-shi, 573-1191, Japan

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Hiroshima, 730-8518, Japan

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Kasama-shi, 309-1793, Japan

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Kita-gun, 761-0793, Japan

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Kitaadachi-gun, 362-0806, Japan

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Kōtoku, 135-8550, Japan

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Matsuyama, 791-0280, Japan

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Niigata, 951-8566, Japan

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Osaka, 541-8567, Japan

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Osakasayama-shi, 589-8511, Japan

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Ota-shi, 373-8550, Japan

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Sakaishi, 591-8025, Japan

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Sendai, 980-8574, Japan

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Shiwa-gun, 028-3695, Japan

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Suita-shi, 565-0871, Japan

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Sunto-gun, 411-8777, Japan

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Toyoake-shi, 470-1192, Japan

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Yokohama, 232-0024, Japan

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Yokohama, 241-8515, Japan

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George Town, 10450, Malaysia

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Ipoh, 30450, Malaysia

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Kuala Lumpur, 50586, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Sabak Bernam, 88996, Malaysia

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Amsterdam, 1081 HV, Netherlands

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Arnhem, 6815 AD, Netherlands

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Leiden, 2333 ZA, Netherlands

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Arequipa, AREQUIPA54, Peru

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Callao, CALLAO 02, Peru

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Lima, 15036, Peru

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Lima, LIMA 29, Peru

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Lima, Lima 34, Peru

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Lima, Lima39, Peru

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San Isidro, 15073, Peru

NOT YET RECRUITING

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Bialystok, 15-027, Poland

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Gdansk, 80-219, Poland

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Koszalin, 75-581, Poland

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Olsztyn, 10-228, Poland

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Przemyśl, 37-700, Poland

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Warsaw, 02-034, Poland

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Wroclaw, 50-556, Poland

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Rio Piedras, 00935, Puerto Rico

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Daegu, 41404, South Korea

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Goyang-si, 410-769, South Korea

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Gyeonggi-do, 13620, South Korea

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Jeonnam, 519-763, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 06351, South Korea

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Seoul, 06591, South Korea

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Seoul, 5505, South Korea

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Badalona, 08916, Spain

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Barcelona, 08035, Spain

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Madrid, 28034, Spain

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Madrid, 28041, Spain

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Ourense, 32005, Spain

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Santander, 39008, Spain

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Seville, 41013, Spain

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Valencia, 46010, Spain

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Kaohsiung City, 80756, Taiwan

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Kaohsiung City, 824, Taiwan

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Taichung, 40447, Taiwan

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Taichung, 40705, Taiwan

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Tainan, 704, Taiwan

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Tainan, 736, Taiwan

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Taipei, 100, Taiwan

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Taipei, 112, Taiwan

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Taoyuan District, 333, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Banphaeo, 74120, Thailand

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Dusit, 10300, Thailand

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Khon Kaen, 40002, Thailand

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Muang, 22000, Thailand

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Ankara, 06100, Turkey (Türkiye)

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Antalya, 07100, Turkey (Türkiye)

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Diyarbakır, 21280, Turkey (Türkiye)

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Erzurum, 25240, Turkey (Türkiye)

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Istanbul, 34010, Turkey (Türkiye)

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Izmir, 35965, Turkey (Türkiye)

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Mezitli, 33200, Turkey (Türkiye)

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Cambridge, CB2 2QQ, United Kingdom

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Coventry, CV2 2DX, United Kingdom

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Dundee, DD1 9SY, United Kingdom

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London, EC1A 7BE, United Kingdom

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London, W1G 6AD, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Sutton, SM2 5PT, United Kingdom

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Hanoi, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Hồ Chí Minh, 700000, Vietnam

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Việt Trì, 35000, Vietnam

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Vinh, 460000, Vietnam

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MeSH Terms

Interventions

trastuzumab deruxtecanTrastuzumabpembrolizumabFluorouracilCapecitabineCisplatinOxaliplatin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsUracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsCoordination ComplexesOrganic Chemicals

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
The study will be conducted "Sponsor-blinded", such that intervention arm allocation is not known to Sponsor personnel.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 12, 2024

First Posted

January 9, 2025

Study Start

March 1, 2025

Primary Completion (Estimated)

April 27, 2029

Study Completion (Estimated)

December 9, 2030

Last Updated

April 9, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
More information

Locations