Durvalumab + Chemoradiation for Esophageal Cancer

(KUNLUN Trial)

Not currently recruiting at 164 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Disqualifiers: Small cell carcinoma, Adenocarcinoma, Autoimmune disorders, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Concurrent with chemoradiation therapy

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment plan for individuals with a type of esophageal cancer that cannot be surgically removed. It combines durvalumab (an immunotherapy) with chemotherapy and radiation to determine if it is more effective than a placebo with the same treatments. The goal is to assess whether adding durvalumab helps manage cancer more effectively. Individuals diagnosed with advanced esophageal squamous cell carcinoma who are not undergoing surgery may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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 trial's treatments are likely to be safe?

Research shows that durvalumab, when combined with chemotherapy, is generally safe for patients with esophageal squamous cell carcinoma (ESCC). In previous studies, most patients tolerated durvalumab well, and it showed promising results in reducing tumors. This indicates that side effects were not too severe for most participants.

Chemotherapy combinations, such as cisplatin with capecitabine or cisplatin with fluorouracil, are common treatments and are generally considered safe, with known side effects. Patients often experience nausea, fatigue, and a decrease in blood cell counts, but these are usually manageable with proper care.

Overall, the treatments in this trial have undergone prior testing, and their safety is well understood. While side effects can occur, they are usually controllable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using Durvalumab with chemoradiation for esophageal cancer because it offers a new way to boost the body's immune response against cancer cells. Unlike traditional chemotherapy, which directly attacks cancer cells, Durvalumab is an immunotherapy drug that works by blocking the PD-L1 protein, helping the immune system recognize and destroy cancer cells more effectively. This approach could potentially enhance the effectiveness of standard treatments like cisplatin and capecitabine or fluorouracil, making it a promising addition to current therapy options.

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

This trial will compare the effects of adding durvalumab to chemoradiation versus a placebo in treating esophageal cancer. Research has shown that adding durvalumab to chemoradiation might lead to better outcomes. One study found that patients receiving durvalumab experienced a greater decrease in tumor size compared to those who did not. Another study found that durvalumab, when combined with chemotherapy, was manageable and showed activity against tumors in esophageal cancer. These findings suggest that durvalumab could be a beneficial addition to treatment for locally advanced esophageal squamous cell carcinoma (ESCC). ^{1 2 6 7 8}

Who Is on the Research Team?

Luhua Wang, MD

Principal Investigator

Cancer Hospital of Chinese Academy of Medical Science

Nabil Saba, MD

Principal Investigator

Department of Hematology and Medical Oncology, Emory University

Are You a Good Fit for This Trial?

This trial is for adults with advanced esophageal squamous cell carcinoma who can't have surgery or choose not to. They should be fit enough for chemoradiation, have a lesion that can be measured, and expect to live more than 3 months. They must not have other cancers, serious infections like HIV or hepatitis, known allergies to the drugs used in the study, autoimmune diseases, or conditions that could lead to esophagus perforation.

Inclusion Criteria

Patients with at least an evaluable lesion per RECIST 1.1

You are expected to live for at least 3 more months.

My cancer cannot be removed by surgery or I chose not to have surgery, and I am eligible for chemoradiation.

Exclusion Criteria

I have had another type of cancer.

My esophageal cancer has been confirmed by lab tests.

Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab or placebo concurrently with definitive chemoradiation therapy

Concurrent with chemoradiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to approximately 72 months

What Are the Treatments Tested in This Trial?

Interventions

• cisplatin + capecitabine
• cisplatin + fluorouracil
• Durvalumab
• Placebo
• Radiation

Trial Overview The study is testing Durvalumab (a type of immunotherapy) against a placebo. Both are given alongside standard chemotherapy (cisplatin with fluorouracil or capecitabine) and radiation therapy. The goal is to see if adding Durvalumab improves treatment outcomes compared to just chemo and radiation alone.

How Is the Trial Designed?

Group I: Arm 1: Durvalumab + definitive CRT Experimental Treatment 4 Interventions

Durvalumab + concurrent chemoradiation

Group II: Arm 2: Placebo + definitive CRT Placebo Group 4 Interventions

Placebo + concurrent chemoradiation

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 phase II study involving 86 patients with esophageal squamous cell carcinoma, adjuvant durvalumab did not show a significant improvement in disease-free survival or overall survival compared to placebo after neoadjuvant chemoradiotherapy.

However, in patients with positive PD-L1 expression, durvalumab was associated with a higher overall survival rate, suggesting that PD-L1 status may help predict the effectiveness of durvalumab in this treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant durvalumab for esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy: a placebo-controlled, randomized, double-blind, phase II study. Park, S., Sun, JM., Choi, YL., 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]

In a Phase II trial involving 74 patients with unresectable, locally advanced non-small cell lung cancer (NSCLC), durvalumab immunotherapy combined with radiotherapy resulted in a promising 12-month progression-free survival (PFS) rate of 72.1%, indicating its efficacy as a treatment option.

The treatment was generally well-tolerated, with a high objective response rate of 90.9%, although 52.9% of patients experienced severe adverse events (grade 3 or 4), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial. Tachihara, M., Tsujino, K., Ishihara, T., et al.[2023]

In a study of 107 patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT) and intensity-modulated radiotherapy (IMRT), the median progression-free survival (PFS) was 20.7 months, indicating effective treatment outcomes.

Factors associated with longer PFS included a favorable response to CCRT, a radiation dose of 62 Gy or more, and having stage IIIA NSCLC, while shorter durations of durvalumab treatment and lower radiation doses were linked to increased mortality risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study. Takeda, Y., Kusaba, Y., Tsukita, Y., et al.[2022]

In a study of 121 patients with stage III non-small cell lung cancer treated with durvalumab, those with over 50% PD-L1 expression had significantly better outcomes, with a 1-year survival rate of 97% compared to 73% and 78% for lower expression groups.

Higher PD-L1 expression (>50%) was strongly associated with improved progression-free survival and overall survival, indicating that PD-L1 levels could be a key factor in predicting the effectiveness of durvalumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. Jazieh, K., Gad, M., Saad, A., 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]

In a phase 3 study of 713 patients with stage III non-small-cell lung cancer, durvalumab significantly improved progression-free survival compared to placebo, with a median of 16.8 months versus 5.6 months, respectively.

Durvalumab also showed a higher response rate (28.4% vs. 16.0%) and longer median time to death or distant metastasis (23.2 months vs. 14.6 months), while safety profiles were similar between durvalumab and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. Antonia, SJ., Villegas, A., Daniel, D., et al.[2022]

The ARION trial is investigating the efficacy of the anti-PD-L1 drug durvalumab combined with standard chemoradiotherapy (CRT) in patients with locally advanced unresectable esophageal cancer, aiming to improve progression-free survival from 50% to 68% at 12 months.

This multicenter phase II trial will also explore potential biomarkers, such as PD-L1 expression and gut microbiota, to better understand the immune response and treatment outcomes, highlighting the importance of combining immunotherapy with traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Radiochemotherapy to Immunotherapy in unresectable locally advanced Oesophageal carciNoma-randomized phase 2 trial ARION UCGI 33/PRODIGE 67: the study protocol. Modesto, A., Tougeron, D., Tremolières, P., et al.[2023]

Citations

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2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS4172

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7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8484871/

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8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.6260

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