Durvalumab + Tremelimumab for Stomach and Esophageal Cancer

Overseen By University of California Irvine Medical

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, Irvine

Disqualifiers: Metastatic disease, Prior treatment, Autoimmune, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of two drugs, Durvalumab and Tremelimumab, can enhance the immune response in individuals with certain types of stomach and esophageal cancer. It targets those who have not yet received treatment for their cancer, possess a specific gene mutation (ARID1A), and whose cancer has not spread. Participants must agree to undergo biopsy procedures to help researchers assess the drugs' effects. As an Early Phase 1 trial, this research focuses on understanding the treatment's mechanism in people, providing participants an opportunity to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that using Durvalumab and Tremelimumab together appears safe. Earlier studies found the doses of these drugs to be safe and well-tolerated. For example, one study confirmed that a specific dose was safe for further testing. Another study demonstrated that this combination was safe and effective in patients with certain types of stomach cancer.

While these results are promising, it's important to remember that this trial remains in its early stages. The treatment is being tested in humans for the first time, and researchers are still collecting safety information. So far, the data suggest that the treatment is generally safe, but more research is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Durvalumab and Tremelimumab for stomach and esophageal cancer because these treatments work differently from traditional chemotherapy. Unlike standard treatments that attack cancer cells directly, these drugs are immune checkpoint inhibitors. They help unleash the body's immune system to recognize and destroy cancer cells. Specifically, Durvalumab targets the PD-L1 protein, while Tremelimumab inhibits CTLA-4, both of which can block cancer-fighting immune responses. This approach has the potential to offer a more targeted attack on cancer with possibly fewer side effects than conventional therapies.

What evidence suggests that Durvalumab and Tremelimumab might be effective for stomach and esophageal cancer?

Research has shown that using durvalumab and tremelimumab together holds promise for treating certain cancers. In one study, over half of the patients experienced a reduction or disappearance of their cancer. Another study found that these drugs helped some patients avoid surgery, with 76% showing a complete response. Additionally, a treatment plan including durvalumab reduced the risk of death by 22% in early stomach cancer compared to chemotherapy alone. In this trial, participants will receive a combination of durvalumab and tremelimumab to evaluate its effectiveness in targeting and shrinking stomach and esophageal tumors, particularly those with ARID1A mutations. ^{1 2 3 4 6}

Who Is on the Research Team?

Farshid Dayyani

Principal Investigator

Chao Family Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with untreated esophageal, gastroesophageal junction, or gastric adenocarcinomas that haven't spread elsewhere and have ARID1A mutations. Participants must be willing to undergo biopsy procedures.

Inclusion Criteria

My cancer is not MSI-High.

No clinically significant autoimmune disease

My cancer in the esophagus or stomach has a specific genetic change.

Exclusion Criteria

Patients with uncontrolled autoimmune disease per investigator discretion

My cancer has spread to other parts of my body.

I have had treatment for cancer in my esophagus, GEJ, or stomach.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of Tremelimumab 300 mg IV and Durvalumab 1500 mg IV on day 1

1 day

1 visit (in-person)

Post-Treatment Biopsy

Participants undergo a biopsy to assess T-cell infiltration and tumor microenvironment composition

2-6 weeks post-treatment

Follow-up

Participants are monitored for safety, adverse events, and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Tremelimumab

Trial Overview

The trial tests the effectiveness of a single dose of two immune checkpoint inhibitors, Durvalumab and Tremelimumab, in increasing T cells within tumors for certain stomach cancers.

How Is the Trial Designed?

Group I: Tremelimumab and Durvalumab Experimental Treatment 2 Interventions

Tremelimumab 300 mg IV, single-dose, day 1 Durvalumab 1500mg IV, single-dose, day 1

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

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]

Durvalumab monotherapy and the combination of durvalumab with tremelimumab showed acceptable safety profiles, with grade ≥3 treatment-related adverse events occurring in 19.0% of patients with biliary tract cancer (BTC) and 25.0% with head and neck squamous cell carcinoma (HNSCC).

The combination therapy demonstrated a higher objective response rate (ORR) of 10.8% in BTC and 20.3% in esophageal squamous cell carcinoma (ESCC), indicating potential clinical benefit for patients with advanced cancers who had disease progression after prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and efficacy of durvalumab, either as monotherapy or in combination with tremelimumab, in patients from Asia with advanced biliary tract, esophageal, or head-and-neck cancer. Doki, Y., Ueno, M., Hsu, CH., et al.[2022]

In a study of 113 patients with chemotherapy-refractory gastric or gastroesophageal junction cancer, the combination of durvalumab and tremelimumab showed low overall response rates, with the highest at 15.8% for the combination therapy in the third-line treatment group.

Despite the low efficacy, the study did not identify any new safety concerns, and it suggests that using a tumor-based IFNγ gene signature could be a promising approach to enhance treatment responses in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Durvalumab and Tremelimumab Alone or in Combination in Patients with Advanced Gastric and Gastroesophageal Junction Adenocarcinoma. Kelly, RJ., Lee, J., Bang, YJ., et al.[2021]

This phase II study aims to evaluate the effectiveness of combining durvalumab and tremelimumab with neoadjuvant chemotherapy in improving progression-free survival (PFS) in patients with advanced-stage ovarian cancer, specifically those with stage IIIC/IV epithelial ovarian cancer.

The study will involve 24 patients and will assess immune biomarkers and changes in the tumor microenvironment through serial biopsies, with the primary goal of achieving a 12-month PFS rate, while also monitoring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of neoadjuvant chemotherapy plus durvalumab and tremelimumab in advanced-stage ovarian cancer: a Korean Gynecologic Oncology Group Study (KGOG 3046), TRU-D. Lee, JY., Kim, JW., Lim, MC., et al.[2020]

The combination of durvalumab and tremelimumab showed improved disease control rates in patients with head and neck squamous cell carcinoma compared to tremelimumab alone, indicating its potential efficacy in this cancer type.

The combination therapy had a tolerable safety profile, with no significant increase in treatment-related adverse events compared to monotherapy, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. Wang, BC., Li, PC., Fan, JQ., et al.[2022]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7748730/

Safety and Efficacy of Durvalumab and Tremelimumab ...

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annalsofoncology.org/article/S0923-7534%2824%2904953-6/fulltext

Tremelimumab and durvalumab as neoadjuvant or non- ...

In cohort 2, 76% patients achieved complete clinical response and started NOM, with gastrectomy-free survival of 64.2%. Abstract. Background. In ...

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Results: Forty-eight pts were enrolled. Overall response rate (ORR) was 52.1% with complete response in 4 (8.3%) pts, partial response in 21 ( ...

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IMFINZI® (durvalumab)-based regimen reduced the risk of death by 22% in early gastric cancer vs. chemotherapy alone in MATTERHORN Phase III ...

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In cohort 2, 76% patients achieved complete clinical response and started NOM, with gastrectomy-free survival of 64.2%. Background. In resectable gastric/ ...

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cancernetwork.com

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Tremelimumab/Durvalumab Demonstrates Safety, Activity ...

Pre-operative tremelimumab plus durvalumab elicited encouraging safety and activity in patients with microsatellite instability–high resectable ...