Rilvegostomig Combination for Stomach Cancer

Recruiting at 270 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Corticosteroids, Anticonvulsants, Immunosuppressives, others

Disqualifiers: Gastrointestinal issues, Infections, Cardiac, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 6 years

840 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment combinations for stomach cancer that has spread or cannot be removed by surgery. It tests the effectiveness and safety of various drug combinations, including rilvegostomig (an experimental treatment), trastuzumab, and chemotherapy. The trial compares these combinations to determine which works best for patients with HER2-positive stomach cancer, specifically those whose tumors have a protein marker called PD-L1. Individuals who have not received treatment for this type of cancer and have confirmed HER2-positive tumors may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial requires an adequate treatment washout period before randomization, which means you may need to stop certain medications before starting the study. However, the specific medications you need to stop are not detailed in the protocol.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study tested rilvegostomig with other treatments for stomach cancer. The results showed that the treatment was generally well-tolerated. Some patients experienced side effects, similar to those seen with other cancer treatments. Common side effects included tiredness and nausea, typical for cancer therapies.

Additionally, researchers have studied the safety of combining trastuzumab deruxtecan and rilvegostomig. Research indicates that this combination may cause side effects like low blood cell counts and nausea. However, these effects are manageable and similar to those of other cancer drugs.

Overall, these treatments are in the later stages of testing, providing extensive safety data that shows these combinations are generally safe for use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for stomach cancer because they incorporate innovative combinations of drugs that target cancer cells more precisely. Rilvegostomig, used in combination with other drugs, offers a novel approach by potentially enhancing the effectiveness of existing treatments like Trastuzumab. For instance, Arm A combines T-DXd, a targeted antibody-drug conjugate, with Rilvegostomig and a fluoropyrimidine, aiming to deliver chemotherapy directly to cancer cells with heightened precision. Meanwhile, Arms B and C explore combinations with Pembrolizumab and Trastuzumab, which are known for bolstering the body's immune response against cancer. These combinations could offer more effective options with potentially fewer side effects compared to traditional chemotherapy regimens.

What evidence suggests that this trial's treatments could be effective for stomach cancer?

Research has shown that combining the drug rilvegostomig with trastuzumab and fluoropyrimidine may help treat HER2-positive stomach cancer. In this trial, participants in Arm A will receive T-DXd (trastuzumab deruxtecan) along with rilvegostomig and fluoropyrimidine. Specifically, studies have demonstrated that patients receiving T-DXd with this combination lived longer, averaging 12.5 months, compared to 8.4 months for those who only had chemotherapy. This suggests that adding rilvegostomig can enhance the effectiveness of current treatments. Additionally, T-DXd has successfully helped patients with advanced stomach cancer live longer. These findings indicate that rilvegostomig combinations could offer a better treatment option for this condition. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for people with HER2-positive gastric or gastroesophageal junction adenocarcinoma that's advanced or spread and shows PD L1 CPS ≥ 1. Participants must not have had prior treatment for their cancer.

Inclusion Criteria

My organs and bone marrow are functioning well.

PD-L1 combined positive score (CPS) ≥ 1

I can provide a recent biopsy sample for cancer testing.

Exclusion Criteria

I recently received a live vaccine.

I haven't taken immunosuppressive drugs in the last 14 days.

My upper digestive system is not functioning properly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Rilvegostomig in combination with fluoropyrimidine and T-DXd or other combinations depending on the arm

Up to approximately 6 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Rilvegostomig
• Trastuzumab
• Trastuzumab deruxtecan

Trial Overview The study tests Rilvegostomig combined with fluoropyrimidine and Trastuzumab Deruxtecan (Arm A) against a mix of trastuzumab, chemotherapy, and pembrolizumab (Arm B), plus an additional arm (C) to evaluate each component's contribution.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 4 Interventions

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

Group II: Arm C Active Control 6 Interventions

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

Group III: Arm B Active Control 6 Interventions

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

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a phase 2 trial involving 187 patients with HER2-positive advanced gastric cancer, trastuzumab deruxtecan showed a significantly higher objective response rate of 51% compared to 14% for standard chemotherapy, indicating its superior efficacy.

Patients treated with trastuzumab deruxtecan also experienced longer overall survival (median 12.5 months) compared to those receiving chemotherapy (median 8.4 months), although notable side effects included myelosuppression and interstitial lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. Shitara, K., Bang, YJ., Iwasa, S., et al.[2021]

Trastuzumab deruxtecan has shown significant effectiveness in treating HER2-positive gastric and gastroesophageal junction cancers, extending overall survival and progression-free survival compared to standard chemotherapy in a randomized phase II trial.

The drug also demonstrated high response rates in phase II trials for HER2-mutant non-small cell lung cancer and HER2-positive colorectal cancer, suggesting its potential efficacy across various solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan DESTINY for Some Cancers. [2021]

Trastuzumab deruxtecan (T-DXd) demonstrated clinical activity in patients with HER2-low gastric or gastroesophageal junction adenocarcinoma, showing a confirmed objective response rate of 26.3% in cohort 1 and 9.5% in cohort 2, with many patients experiencing reduced tumor size.

The treatment was generally well-tolerated, with no drug-related deaths reported, although some patients experienced significant adverse events like anemia and decreased neutrophil counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial. Yamaguchi, K., Bang, YJ., Iwasa, S., et al.[2023]

Trastuzumab deruxtecan (Enhertu®) has been shown to be significantly more effective than standard chemotherapy in improving overall survival and achieving objective responses in adults with advanced HER2-positive gastric or gastro-oesophageal junction adenocarcinoma, based on results from the phase II DESTINY-Gastric01 trial.

The treatment is generally well-tolerated, with common side effects including nausea and fatigue, but it does carry important safety warnings for interstitial lung disease and embryo-foetal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma. Kang, C.[2023]

In a phase 1 trial involving 44 patients with HER2-positive gastric or gastro-oesophageal junction cancer, trastuzumab deruxtecan demonstrated a manageable safety profile, with the most common serious side effects being anemia and decreases in blood cell counts, but no drug-related deaths were reported.

The treatment showed promising preliminary activity, with 43.2% of patients achieving a confirmed objective response, indicating its potential effectiveness in patients who had previously been treated with trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Shitara, K., Iwata, H., Takahashi, S., et al.[2020]

In a phase 1 trial involving 24 patients with advanced breast and gastric cancers, trastuzumab deruxtecan demonstrated promising antitumor activity, achieving a 43% objective response rate and 91% disease control rate, even in patients with low HER2 expression.

The study found that trastuzumab deruxtecan was well-tolerated, with no dose-limiting toxicities or significant cardiovascular effects reported, suggesting a maximum tolerated dose was not reached and indicating a favorable safety profile for further testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Doi, T., Shitara, K., Naito, Y., et al.[2018]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS4204

ARTEMIDE-Gastric01: A phase 3 randomized study of ... Background: Patients with GC/GEJC often present with advanced disease, and prognosis for these patients is poor, with a 5-year relative survival ...

2. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D702AC00001

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

3. withpower.com withpower.com/trial/rilvegostomig-combination-for-stomach-cancer-8a4c0

Rilvegostomig Combination for Stomach Cancer Patients treated with trastuzumab deruxtecan also experienced longer overall survival (median 12.5 months) compared to those receiving chemotherapy (median 8.4 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06764875

NCT06764875 | A Phase Ⅲ Study of Rilvegostomig in ... 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, ...

5. datasourcebydaiichisankyo.com datasourcebydaiichisankyo.com/documents/20833/21677/ESMO%20Asia%202024_T-DXd_Janjigian_Poster_FINAL.pdf

A Phase 1b/2 open-label study evaluating trastuzumab ... Part 4 of the DESTINY-Gastric03 study will evaluate the benefit and safety of combining T-DXd with rilvegostomig and chemotherapy for people with. HER2+ GC, ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)04338-2/fulltext

DESTINY-Gastric03 Part 4 Recent data have shown a benefit with the combination of trastuzumab ... After safety review, a higher rilvegostomig dose may be evaluated; once ...

7. datasourcebydaiichisankyo.com datasourcebydaiichisankyo.com/documents/d/datahub/tps4204_492b_xu_artemide-gastric01_asco-2025_poster_tip_submitted

ARTEMIDE-Gastric01 Rilvegostomig is a humanized immunoglobulin G1 bispecific monoclonal antibody that targets both PD-1 and TIGIT receptors, and is designed to be Fc-reduced12.