Rilvegostomig Combination for Stomach Cancer

Recruiting at 190 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

Trial Summary

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.

What data supports the effectiveness of the drug Rilvegostomig Combination for Stomach Cancer?

Trastuzumab deruxtecan, a component of the treatment, has shown effectiveness in treating advanced HER2-positive gastric cancer by significantly improving survival and response rates compared to standard chemotherapy, as demonstrated in several clinical trials. ^{1 2 3 4 5}

What safety information is available for Rilvegostomig (Trastuzumab Deruxtecan)?

Trastuzumab deruxtecan has been associated with some safety concerns, including a risk of interstitial lung disease (lung inflammation) and embryo-fetal toxicity (harm to unborn babies). Additionally, nausea and vomiting were reported in up to 78% of patients in clinical trials, with about 8% experiencing severe symptoms. ^{1 2 5 6 7}

What makes the Rilvegostomig combination unique for treating stomach cancer?

The Rilvegostomig combination is unique because it includes trastuzumab deruxtecan, an antibody-drug conjugate that targets HER2 (a protein that can promote cancer growth) and delivers a powerful cancer-killing drug directly to the cancer cells. This approach may offer better outcomes for patients with HER2-positive stomach cancer compared to standard chemotherapy. ^{1 2 3 5 7}

What is the purpose of this trial?

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.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 (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 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 (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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. [2021]

2. United States 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan DESTINY for Some Cancers. [2021]

4. France pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Management of Chemotherapy-Induced Nausea and Vomiting with Trastuzumab Deruxtecan: A Case Series. [2022]

7. England 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. [2018]