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

34 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination of Durvalumab and Tremelimumab for stomach and esophageal cancer?

Research shows that the combination of Durvalumab and Tremelimumab has been beneficial for patients with various solid tumors, including esophageal cancer, and is generally safe. This suggests potential effectiveness for stomach and esophageal cancer as well. ^{1 2 3 4 5}

Is the combination of Durvalumab and Tremelimumab safe for humans?

The combination of Durvalumab and Tremelimumab has been studied for safety in various cancers, showing a higher rate of serious side effects compared to Durvalumab alone. Common side effects include reduced appetite and diarrhea, with some patients experiencing severe side effects like neutropenia (low white blood cell count). ^{1 3 4 6 7}

How is the drug combination of Durvalumab and Tremelimumab unique for treating stomach and esophageal cancer?

The combination of Durvalumab and Tremelimumab is unique because it uses two immunotherapy drugs that work together to boost the body's immune system to fight cancer, targeting specific pathways that help cancer cells evade immune detection. This approach is different from traditional chemotherapy, which directly attacks cancer cells, and it offers a new option for patients with advanced stages of these cancers. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a proof of principle clinical trial determining efficacy of single dose dualimmune checkpoint inhibitors to increase intra-tumoral T cells in esophageal, gastroesophageal junction, and gastric adenocarcinomas. These are subjects who have not previously been treated for their disease, who are willing to undergo biopsy procedures, who's disease has not spread to other parts of the body, who's tumors have ARID1A mutations.

Research Team

Farshid Dayyani

Principal Investigator

Chao Family Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

References

1. United States 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. [2022]

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

Safety and tolerability of first-line durvalumab with tremelimumab and chemotherapy in esophageal squamous cell carcinoma. [2023]

3. United States 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. [2021]

4. United States 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. [2022]

5. Korea (South) 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. [2020]

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]

7. Switzerland 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. [2023]