Durvalumab + Chemoradiation for Esophageal Cancer

(KUNLUN Trial)

Recruiting at 120 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

640 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if adding durvalumab to standard cancer treatments helps patients with advanced esophageal cancer that can't be surgically removed. Durvalumab boosts the immune system's ability to attack cancer cells.

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 Durvalumab when used with chemoradiation for esophageal cancer?

Research shows that adding Durvalumab, an immune checkpoint inhibitor, to chemoradiotherapy (a combination of chemotherapy and radiation) may provide clinical benefits for patients with locally advanced esophageal cancer. This is based on its effectiveness in other cancers like non-small cell lung cancer, where it has been shown to improve outcomes when used after chemoradiotherapy. ^{1 2 3 4 5}

Is the combination of Durvalumab and chemoradiation generally safe for humans?

Durvalumab, when used with chemotherapy and radiotherapy, has shown a manageable safety profile in various cancers, including lung cancer. However, some patients experience serious side effects, such as neutropenia (low white blood cell count) and other adverse events, which are often related to the chemotherapy component. ^{1 3 4 6 7}

What makes the treatment with Durvalumab and chemoradiation unique for esophageal cancer?

This treatment combines Durvalumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with chemoradiation, which is the standard care for esophageal cancer. The addition of Durvalumab is expected to enhance the effectiveness of the standard treatment by providing a new systemic strategy to improve patient outcomes. ^{1 2 3 4 8}

Research Team

Nabil Saba, MD

Principal Investigator

Department of Hematology and Medical Oncology, Emory University

Luhua Wang, MD

Principal Investigator

Cancer Hospital of Chinese Academy of Medical Science

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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, 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 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]

References

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

Adjuvant durvalumab for esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy: a placebo-controlled, randomized, double-blind, phase II study. [2023]

2. Ireland 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. [2022]

3. England 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. [2023]

4. United States 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. [2023]

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

Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. [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]

7. England pubmed.ncbi.nlm.nih.gov

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

8. China 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. [2022]