Durvalumab + FLOT for Gastric Cancer

Recruiting at 143 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

957 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether adding durvalumab to a standard chemotherapy mix around the time of surgery can help patients with stomach or gastroesophageal cancer. Durvalumab helps the immune system fight cancer, while the chemotherapy drugs kill cancer cells.

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.

What data supports the effectiveness of the drug Durvalumab in combination with FLOT chemotherapy for gastric cancer?

Early-phase clinical studies suggest that combining Durvalumab, an immune checkpoint inhibitor, with FLOT chemotherapy may improve outcomes for patients with advanced or metastatic gastric cancer. Additionally, Durvalumab has shown effectiveness in other cancers, such as non-small-cell lung cancer, when used with chemotherapy and other treatments. ^{1 2 3 4 5}

Is the combination of Durvalumab and FLOT chemotherapy safe for treating gastric cancer?

Durvalumab has been studied in various cancers and generally shows a manageable safety profile. In a study combining Durvalumab with chemotherapy for advanced gastric cancer, 63.6% of patients experienced serious side effects, mainly neutropenia (low white blood cell count), but these were mostly related to the chemotherapy. Only one immune-related side effect was reported, indicating that the combination has an expected safety profile. ^{2 3 4 5 6}

What makes the drug Durvalumab + FLOT unique for treating gastric cancer?

Durvalumab + FLOT is unique because it combines an immune checkpoint inhibitor (durvalumab) with a standard chemotherapy regimen (FLOT) to potentially improve outcomes in gastric cancer. Durvalumab works by enhancing the body's immune response against cancer cells, which is different from traditional chemotherapy that directly targets and kills cancer cells. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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, 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

MATTERHORN: phase III study of durvalumab plus FLOT chemotherapy in resectable gastric/gastroesophageal junction cancer. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

3. United States 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

6. Switzerland 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. [2022]