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A Phase Ⅲ Study of Rilvegostomig in Combination With Fluoropyrimidine and Trastuzumab Deruxtecan as the First-line Treatment for HER2-positive Gastric Cancer

PHASE3RECRUITING

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.

Study details:

The purpose of this study is to assess 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. This study will be conducted at up to 200-250 sites globally in approximately 25 countries.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  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 RECIST v1.1.
  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

  1. Lack of physiological integrity of the upper gastrointestinal tract.
  2. Known dihydropyrimidine dehydrogenase enzyme deficiency.
  3. Contraindication to pembrolizumab or trastuzumab, contraindications to fluoropyrimidine (5-FU and capecitabine) or platinum (cisplatin and oxaliplatin) treatment as per local label.
  4. 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.
  5. Persistent toxicities caused by previous anti-cancer therapy.
  6. 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.
  7. Uncontrolled infection including tuberculosis and active hepatitis A infection.
  8. Uncontrolled infection requiring intravenous (IV) antibiotics, anti-virals, or antifungals.
  9. Recent receipt of live, attenuated vaccine.
  10. Chronic/active HBV or HCV infection unless controlled.
  11. Clinically significant cardiac or psychological conditions.
  12. Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
  13. History of (non-infectious) ILD/pneumonitis, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
  14. Lung-specific intercurrent clinically significant illnesses.
  15. Any active non-infectious skin disease requiring systemic treatment.
  16. A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART).
  17. History of any of the following: drug-induced severe cutaneous adverse reaction.
  18. Any concurrent antic-ancer treatment with the exception of receptor activator of nuclear factor kappa-B ligand inhibitors.
  19. 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.
  20. Current or prior use of immunosuppressive medication within 14 days before study intervention.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE3

trial

Study ID

NCT06764875

Intervention or treatment

DRUG: Rilvegostomig

DRUG: Trastuzumab deruxtecan

DRUG: Trastuzumab

DRUG: Pembrolizumab

DRUG: 5-fluorouracil

DRUG: Capecitabine

DRUG: Cisplatin

DRUG: Oxaliplatin

Conditions

  • HER2-positive Gastric Cancer
  • Gastroesophageal Junction Adenocarcinoma

  • Condition: HER2-positive Gastric Cancer, Gastroesophageal Junction Adenocarcinoma

  • DRUG: Rilvegostomig and other drugs

  • Darlinghurst, Australia and more

  • Sponsor: AstraZeneca

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Research Site

Select from list below to view details:

  • Research Site

    Darlinghurst, Australia

  • Research Site

    Heidelberg, Australia

  • Research Site

    Murdoch, Australia

  • Research Site

    Westmead, Australia

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Who is running the clinical trial?

A

AstraZeneca

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Arm A
  • T-DXd + Rilvegostomig + Fluoropyrimidine (Capecitabine OR 5-FU)
Drug: Rilvegostomig, Drug: Trastuzumab deruxtecan, Drug: 5-fluorouracil, Drug: Capecitabine
    ACTIVE_COMPARATOR: Arm B
    • Pembrolizumab + Trastuzumab + FP (5-FU plus cisplatin) or CAPOX (capecitabine plus oxaliplatin)
    Drug: Trastuzumab, Drug: Pembrolizumab, Drug: 5-fluorouracil, Drug: Capecitabine, Drug: Cisplatin, Drug: Oxaliplatin
      ACTIVE_COMPARATOR: Arm C
      • Rilvegostomig + Trastuzumab + FP (5-FU plus cisplatin) or CAPOX (capecitabine plus oxaliplatin)
      Drug: Rilvegostomig, Drug: Trastuzumab, Drug: 5-fluorouracil, Drug: Capecitabine, Drug: Cisplatin, Drug: Oxaliplatin

        What is the study measuring?

        Primary Outcome

        MeasureDescriptionTime Frame
        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 Outcome

        MeasureDescriptionTime Frame
        Objective Response Rate (ORR)ORR according to RECIST v1.1. ORR is defined as the proportion of participants who have a complete response (CR) or partial response (PR).Up to approximately 6 years
        Duration of Response (DoR)DoR according to RECIST v1.1. DoR will be defined as the time from the date of first documented response until date of documented progression per RECIST v1.1 or death due to any cause.Up to approximately 6 years
        Proportion of all randomized participants alive and progression-free at 6 months (PFS6)Proportion of all randomized participants alive and progression-free at 6 months calculated for progression.Up to 6 months
        Proportion of all randomized participants alive and progression-free at 12 months (PFS12)Proportion of all randomized participants alive and progression-free at 12 months calculated for progression.Up to 12 months
        Time to second progression or death (PFS2)PFS2 is defined as the time from randomization to the earliest of the progression event (following the initial progression), after the first subsequent therapy, or death, where the first objective progression includes progression occurring after 2 missed visits.Up to approximately 6 years
        Occurrence of adverse events (AEs) and serious adverse events (SAEs)Occurrence of AEs and SAEs will be graded according to the revised NCI CTCAE v5.0.Up to approximately 6 years
        Pharmacokinetics (PK) of rilvegostomig, T-DXd, total anti-HER2 antibody, DXd, 5-FU, and capecitabine in serumConcentration of rilvegostomig, T-DXd, total anti-HER2 antibody, DXd, fluoropyrimidine, and capecitabine in serum or plasma.Up to approximately 6 years
        Immunogenicity of rilvegostomig and T-DXd assessed by the presence of antidrug antibodies (ADAs) for rilvegostomig and T-DXdPresence of antidrug antibodies (ADAs) for rilvegostomig and T-DXd (confirmatory results: titers and neutralizing antibodies for confirmed positive samples).Up to approximately 6 years
        Increase in enteral feeding assistance and eating difficultiesTime to first-confirmed worsening of eating symptoms or initiation of feeding assistance among all participants, as randomized.Up to approximately 6 years
        Proportion of time on study intervention with high side-effect botherProportion of time on study intervention with high side-effect bother relative to low side-effect burden as measured by the Patient Global Impression of Treatment Tolerability (PGI-TT).Up to approximately 6 years
        Overall Survival at 12 months (OS12)Proportion of all randomized participants alive at 12 months.Up to 12 months
        Overall Survival at 24 months (OS24)Proportion of all randomized participants alive at 24 months.Up to 24 months
        Pharmacokinetics (PK) of rilvegostomig, T-DXd, total anti-HER2 antibody, DXd, 5-FU, and capecitabine in serumPK parameters (peak and trough concentrations).Up to approximately 6 years
        Are you running this trial?If you're a clinic or sponsor, you can claim this study.
        Claim this trial

        References

        Clinical Trials Gov: A Phase Ⅲ Study of Rilvegostomig in Combination With Fluoropyrimidine and Trastuzumab Deruxtecan as the First-line Treatment for HER2-positive Gastric Cancer

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