Novel Agents for Stomach Cancer

Recruiting at 53 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disorders, CNS pathology, others

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

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

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new drug combinations to determine their safety and effectiveness in treating stomach and esophagus cancers before and after surgery. It includes different treatment arms using various chemotherapy drugs like 5-Fluorouracil and Capecitabine, along with newer agents such as AZD0901, Rilvegostomig, and Trastuzumab Deruxtecan. The goal is to find better ways to shrink tumors and prevent cancer recurrence. Individuals with surgically removable stomach, gastroesophageal junction, or esophageal adenocarcinoma, who have not yet received treatment, might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop taking my current medications for the trial?

The trial requires that you have not used immunosuppressive medication within 14 days before starting the study. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

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

Previous studies have shown that combining AZD0901 with rilvegostomig and chemotherapy drugs like 5-FU or capecitabine is generally well-tolerated. Most side effects were manageable and similar to those seen with standard chemotherapy treatments. Research on T-DXd combined with rilvegostomig and chemotherapy also indicates it is usually well-tolerated, with common side effects like nausea and fatigue, typical for these treatments.

Studies have found that rilvegostomig plus FLOT chemotherapy can lower the risk of death compared to chemotherapy alone, with side effects similar to those usually experienced with chemotherapy. Overall, these treatments have demonstrated a safety profile in other trials similar to standard cancer treatments, suggesting that while side effects can occur, they are typically manageable. ^{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 combine innovative agents with traditional chemotherapy, potentially enhancing effectiveness. Unlike standard treatments which typically involve single-agent or combination chemotherapy, these investigational therapies integrate AZD0901 and T-DXd, which are novel agents with unique mechanisms of action. AZD0901 and T-DXd, combined with rilvegostomig and traditional drugs like 5-FU or capecitabine, offer a new approach by targeting cancer cells more precisely. This combination aims to enhance the effectiveness of treatment in both the pre- and post-surgery phases, offering a comprehensive approach that could potentially improve patient outcomes.

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

Research has shown promising results for the treatments studied in this trial. In Sub-study 1, the combination of AZD0901 and rilvegostomig, with 5-FU or capecitabine, has the potential to improve outcomes for patients with certain types of stomach cancer. In Sub-study 2, studies have indicated that T-DXd, when used with rilvegostomig and 5-FU or capecitabine, shows early signs of fighting tumors in similar cancers. Additionally, Sub-study 3 involves FLOT chemotherapy combined with rilvegostomig, which has been associated with better treatment completion rates and outcomes compared to standard treatments alone. Each of these treatments shows early promise in treating stomach and related cancers, with ongoing research to confirm their effectiveness. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals with locally advanced, resectable gastroesophageal adenocarcinoma who haven't been treated before. It's focused on those who can undergo surgery and chemotherapy.

Inclusion Criteria

My cancer in the stomach or esophagus is confirmed and can be surgically removed.

I am fully active or can carry out light work.

My cancer is CLDN18.2-positive and HER2-negative for Sub-study 1, or HER2-positive for Sub-study 2.

Exclusion Criteria

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

I have had another type of cancer in the past.

I have or had an autoimmune disease treated with steroids or immunosuppressants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant combination therapy with novel agents or combinations before surgery

8-12 weeks

Surgery

Participants undergo planned gastrectomy or gastroesophagectomy

1 week

Adjuvant Treatment

Participants receive adjuvant combination therapy with novel agents or combinations after surgery

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

38 months

Adjuvant Monotherapy (optional)

Participants may receive Rilvegostomig as adjuvant monotherapy

What Are the Treatments Tested in This Trial?

Interventions

• 5-Fluorouracil (5-FU)
• AZD0901
• Capecitabine
• FLOT Chemotherapy
• Rilvegostomig
• Trastuzumab Deruxtecan (T-DXd)

Trial Overview The study tests new treatments or combinations around surgery time in stomach cancer patients. These include Rilvegostomig, Trastuzumab Deruxtecan (T-DXd), FLOT Chemotherapy, Capecitabine, 5-FU, and AZD0901.

How Is the Trial Designed?

Group I: Sub-study 3: Rilvegostomig plus FLOT chemotherapy Experimental Treatment 2 Interventions

Participants will receive Rilvegostomig plus FLOT chemotherapy as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).

Group II: Sub-study 2: T-DXd plus rilvegostomig and 5-FU or capecitabine Experimental Treatment 4 Interventions

Participants will receive T-DXd plus rilvegostomig and 5-FU or capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).

Group III: Sub-study 1: AZD0901 plus rilvegostomig and 5-FU or capecitabine Experimental Treatment 4 Interventions

Participants will receive AZD0901 plus rilvegostomig and 5-FU or capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant combination therapy (post-surgery period) and later will receive Rilvegostomig as adjuvant monotherapy (as optional).

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

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05702229

Study Details | NCT05702229 | Novel Combinations in ... This is a Phase II, open-label, multi-drug, multi-centre study designed to assess the efficacy, safety, tolerability, pharmacokinetics, and immunogenicity ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS4182

GEMINI-Gastric: A phase 2 study of novel treatment ... GEMINI-Gastric: A phase 2 study of novel treatment combinations in patients with locally advanced unresectable or metastatic gastric cancers.

3. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/imfinzi-improved-efs-in-early-stage-gastric-cancer.html

Imfinzi-based regimen demonstrated statistically significant ... These exciting data from MATTERHORN show that a durvalumab-based perioperative regimen resulted in a clinically meaningful improvement in ...

4. mskcc.org mskcc.org/cancer-care/clinical-trials/25-113

A Phase 2 Study of AZD0901 and Rilvegostomig Plus ... Researchers want to see if combining AZD0901 and rilvegostomig with standard chemotherapy works well in people with gastric or gastroesophageal junction (GEJ) ...

5. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/IMFINZI-durvalumab-based-regimen-demonstrated-statistically-significant-and-clinically-meaningful-improvement-in-event-free-survival-in-resectable-early-stage-gastric-and-gastroesophageal-junction-cancers.html

IMFINZI® (durvalumab)-based regimen demonstrated ... A durvalumab-based perioperative regimen resulted in a clinically meaningful improvement in patient outcomes, including decreasing the risk of the cancer ...

6. clinicaltrials.eu clinicaltrials.eu/inn/azd0901/

Azd0901 – Application in Therapy and Current ... AZD0901 is an innovative drug currently being studied in clinical trials for the treatment of advanced gastric and gastroesophageal junction cancers.