Durvalumab + FLOT for Gastric Cancer

Not currently recruiting at 176 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants

Disqualifiers: Metastasis, Adenosquamous carcinoma, Transplant, others

Stay on Your Current Meds You can continue your current medications while participating

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with resectable gastric or gastroesophageal cancer. The researchers aim to determine if adding durvalumab, an immunotherapy drug, to the standard FLOT chemotherapy improves outcomes. Participants are divided into two groups: one receives durvalumab with FLOT, and the other receives a placebo with FLOT. The trial seeks participants with gastric or gastroesophageal cancer that can be surgically removed and who have not undergone previous cancer treatments. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial requires that you stop using immunosuppressive medications at least 14 days before starting durvalumab. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

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

Research has shown that durvalumab, when combined with FLOT chemotherapy, is generally well-tolerated. Patients using this combination experienced a 22% lower risk of death compared to those who received only chemotherapy. This suggests the treatment is safe and may help extend life. However, like any medication, side effects may occur. Discussing potential risks and benefits with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Durvalumab combined with FLOT chemotherapy for gastric cancer because it introduces a novel approach to treatment. Unlike standard chemotherapy that attacks cancer cells directly, Durvalumab is an immunotherapy that works by targeting and blocking the PD-L1 protein, which helps the immune system recognize and attack cancer cells more effectively. This combination aims to enhance the body's natural defenses while utilizing the established effectiveness of FLOT chemotherapy, potentially leading to better outcomes for patients. This innovative mechanism of action distinguishes it from traditional treatments, offering hope for improved survival rates and quality of life for those battling gastric cancer.

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

Research has shown that combining durvalumab with FLOT chemotherapy holds promise for treating stomach and gastroesophageal cancers. In this trial, participants in Arm A will receive durvalumab plus FLOT chemotherapy, while those in Arm B will receive a placebo with FLOT chemotherapy. Studies have found that the combination of durvalumab and FLOT reduces the risk of death by 22% compared to FLOT chemotherapy alone. Specifically, participants receiving durvalumab plus FLOT lived longer without their disease worsening. After three years, 69% of patients on this treatment remained alive, marking a significant improvement. These findings suggest that adding durvalumab to FLOT chemotherapy can make a real difference in fighting these types of cancers. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for patients with resectable gastric or gastroesophageal junction adenocarcinoma, who haven't had cancer treatment before. They must be in good physical condition (WHO/ECOG status 0 or 1), have a life expectancy of at least 24 weeks, and adequate organ function. Those on recent immunosuppressants, with certain contraindications, metastasis, non-adenocarcinoma cancers, or an organ transplant history can't join.

Inclusion Criteria

You are expected to live for at least 24 weeks.

My organs and bone marrow are working well.

I will have a major surgery to remove my cancer.

Exclusion Criteria

My cancer is either adenosquamous, squamous cell, or a GI stromal tumor.

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

I have received an organ transplant from another person.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive durvalumab or placebo combined with FLOT chemotherapy before surgery

8-12 weeks

Surgery

Participants undergo surgery to remove the tumor

Adjuvant Treatment

Participants receive durvalumab or placebo combined with FLOT chemotherapy after surgery

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• FLOT chemotherapy

Trial Overview The study tests Durvalumab (an immunotherapy drug) combined with FLOT chemotherapy against a placebo plus FLOT chemotherapy in patients undergoing surgery for their cancer. It's designed to see if adding Durvalumab before and after surgery can improve outcomes.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 2 Interventions

Durvalumab and FLOT chemotherapy

Group II: Arm B Placebo Group 1 Intervention

placebo product and FLOT chemotherapy

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

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 safety run-in phase of the DURIGAST PRODIGE 59 study involving 11 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma, 63.6% experienced significant adverse events, primarily neutropenia, indicating a notable safety concern with the treatment combination.

The combination of FOLFIRI with Durvalumab and/or Tremelimumab showed an expected safety profile, allowing progression to the randomized phase II study, although careful monitoring for serious adverse events is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of FOLFIRI + Durvalumab +/- Tremelimumab in Second Line of Patients with Advanced Gastric Cancer: A Safety Run-In from the Randomized Phase II Study DURIGAST PRODIGE 59. Evrard, C., Aparicio, T., Soularue, E., et al.[2022]

The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

Citations

1. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/IMFINZI-durvalumab-based-regimen-reduced-the-risk-of-death-by-22-percent-in-early-gastric-cancer-vs-chemotherapy-alone-in-MATTERHORN-Phase-III-trial.html

IMFINZI® (durvalumab)-based regimen reduced the risk of ... In the final OS analysis, results showed the IMFINZI and FLOT perioperative regimen reduced the risk of death by 22% compared with chemotherapy ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40454643/

Perioperative Durvalumab in Gastric and ... Conclusions: Perioperative durvalumab plus FLOT led to significantly better event-free survival outcomes than FLOT alone among participants ...

3. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/imfinzi-flot-significantly-improves-overall-survival-gastric-gastroesophageal-cancer

Imfinzi Plus FLOT Significantly Improves Overall Survival in ... Imfinzi plus FLOT reduced the risk of death by 22% versus chemotherapy alone (HR 0.78; P=0.021). Three-year overall survival reached 69% ...

4. targetedonc.com targetedonc.com/view/durvalumab-plus-flot-improves-os-in-g-gej-adenocarcinoma

Durvalumab Plus FLOT Improves OS in G/GEJ ... Durvalumab combined with FLOT chemotherapy significantly improved overall survival in resectable gastric/gastroesophageal junction ...

5. asco.org asco.org/about-asco/press-center/news-releases/perioperative-treatment-with-durvalumab-FLOT-chemotherapy

Perioperative Treatment With Durvalumab and FLOT ... The MATTERHORN trial shows that perioperative treatment with FLOT plus durvalumab is better than FLOT alone in reducing the risk of recurrence.

6. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/imfinzi-regimen-reduced-risk-of-progression-recurrence-or-death-by-29-in-early-stage-gastric-cancer-vs-chemotherapy-alone-in-matterhorn-phase-iii-trial.html

Imfinzi regimen reduced risk of progression, recurrence or ... Patients treated with the Imfinzi-based perioperative regimen showed a 29% reduction in the risk of disease progression, recurrence or death versus ...