What side effects are associated with this type of intervention?

Common treatments for esophageal cancer, particularly those involving immune checkpoint inhibitors like Durvalumab (PD-L1 inhibition), can lead to a range of side effects. These include immune-related toxicities such as pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. When combined with chemoradiation therapy, additional side effects may include esophagitis, mucositis, nausea, vomiting, and hematologic toxicities like neutropenia and anemia. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of esophageal cancer. Pembrolizumab, an anti-PD-1 monoclonal antibody, has been approved for use in patients with advanced or metastatic esophageal cancer, particularly those with PD-L1-positive tumors. Nivolumab, another anti-PD-1 antibody, has also been approved for esophageal squamous cell carcinoma (ESCC) after prior chemotherapy. These treatments, like Durvalumab, target the PD-1/PD-L1 pathway to enhance the immune system's ability to fight cancer.

What other types of research exist?

Promising alternatives to Durvalumab for esophageal cancer patients include Pembrolizumab and Nivolumab. Pembrolizumab has shown efficacy in PD-L1-positive tumors in the KEYNOTE-181 and KEYNOTE-059 trials. Nivolumab has demonstrated benefits in both squamous cell carcinoma and adenocarcinoma of the esophagus, as seen in the ATTRACTION-3 and ATTRACTION-2 trials. Combination therapies involving these agents may also be considered.

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Durvalumab + Chemoradiation for Esophageal Cancer (KUNLUN Trial)

Phase 3

Waitlist Available

Led By Luhua Wang, MD

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Unresectable or refusing surgery, and has been deemed suitable for definitive chemoradiation therapy

18 years or older at the time of signing the ICF

Must not have

History of another primary malignancy

Histologically or cytologically confirmed small cell esophageal carcinoma, esophageal adenocarcinoma or other mixed carcinoma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 72 months

Awards & highlights

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Durvalumab may cause immune-related side effects such as inflammation in various organs including lungs and intestines, skin reactions, hormone gland problems like thyroid disorders; also possible are infusion reactions along with typical chemotherapy side effects like nausea, fatigue, blood count changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am 18 years old or older.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My esophageal cancer is confirmed and is at an advanced stage, but not the most severe.

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I can provide a sample of my tumor for PD-L1 testing.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had another type of cancer.

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My esophageal cancer has been confirmed by lab tests.

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I do not have active infections like TB, hepatitis B, C, or HIV.

Select...

I have or had an autoimmune or inflammatory disorder.

Select...

I am at high risk of severe bleeding or organ rupture.

Select...

I do not have any uncontrolled illnesses.

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I have received treatment for esophageal cancer before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 72 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 72 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 72 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Overall survival (OS)

Progression free survival (PFS) per RECIST 1.1 as assessed by BICR

Other study objectives

Adverse events (AEs)

Side effects data

From 2022 Phase 2 trial • 80 Patients • NCT03015129

65%

Fatigue

63%

Abdominal pain

55%

Diarrhea

43%

Pain

40%

Weight loss

35%

Hypertension

30%

Anorexia

30%

Constipation

28%

Nausea

28%

Pruritus

25%

Vomiting

20%

Dyspnea

20%

Urinary tract infection

18%

Rash maculo-papular

15%

Cough

15%

Abdominal Pain

15%

Back pain

15%

Increased Urinary Frequency

15%

Weight gain

13%

Arthralgia

10%

Dizziness

10%

Anxiety

10%

Bladder infection

10%

Nasal congestion

10%

Vaginal discharge

Colitis

Dry mouth

Dry skin

Fever

Anal pain

Edema limbs

Flatulence

Headache

Hot flashes

Myalgia

Small intestinal obstruction

Thromboembolic event

Urinary frequency

Urinary tract pain

Confusion

Renal and urinary disorders - Other, specify

Adrenal insufficiency

Anemia

Ascites

Gastroesophageal reflux disease

Hypomagnesemia

Lymphedema

Memory impairment

Mucositis oral

Pneumonitis

Rash acneiform

Sinus bradycardia

Upper respiratory infection

Urinary urgency

Vaginal hemorrhage

Alanine aminotransferase increased

Aspartate aminotransferase increased

Alkaline phosphatase increased

Colonic perforation

Dysarthria

Blood bilirubin increased

CPK increased

Creatinine increased

Myositis

Rectal hemorrhage

Hypothyroidism

Left ventricular systolic dysfunction

Lethargy

Muscle weakness left-sided

Myocarditis

Rectal pain

Weight Loss

Fall

Generalized muscle weakness

Hyperglycemia

Hyperkalemia

Pain in extremity

Peripheral sensory neuropathy

Pleural effusion

Skin infection

100%

80%

60%

40%

20%

Study treatment Arm

Durvalubmab

Durvalubmab + Tremelimumab

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Arm 1: Durvalumab + definitive CRTExperimental Treatment4 Interventions

Durvalumab + concurrent chemoradiation

Group II: Arm 2: Placebo + definitive CRTPlacebo Group4 Interventions

Placebo + concurrent chemoradiation

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Radiation

2003

Completed Phase 2

~780

Durvalumab

2017

Completed Phase 2

~3750

cisplatin + capecitabine

2014

Completed Phase 1

~40

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for esophageal cancer include immune checkpoint inhibitors, chemotherapy, and radiation therapy. Immune checkpoint inhibitors, such as Durvalumab (a PD-L1 inhibitor), work by blocking the interaction between PD-1 on T-cells and PD-L1 on tumor cells, thereby enhancing the immune system's ability to attack cancer cells. This is particularly important for esophageal cancer patients as it can lead to improved survival rates and potentially fewer side effects compared to traditional therapies. Chemotherapy works by targeting rapidly dividing cells, including cancer cells, but can also affect normal cells, leading to significant side effects. Radiation therapy uses high-energy rays to kill cancer cells and shrink tumors. Combining these treatments can enhance their effectiveness, offering a comprehensive approach to managing esophageal cancer.