What side effects are associated with this type of intervention?

Treatments for Small Cell Lung Cancer (SCLC) using immune checkpoint inhibitors like Durvalumab (PD-L1 inhibitor) and Tremelimumab (CTLA-4 inhibitor) can cause immune-related adverse events (irAEs). Common irAEs include skin reactions (rash, pruritus), gastrointestinal issues (colitis, diarrhea), liver inflammation (hepatitis), endocrine disorders (thyroiditis, adrenal insufficiency), and lung inflammation (pneumonitis). Severe irAEs are less common but may require immunosuppressive therapy. When combined with chemotherapy, these treatments can also lead to increased fatigue, nausea, and hematologic toxicities such as anemia and neutropenia.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of Small Cell Lung Cancer (SCLC). Atezolizumab, a PD-L1 inhibitor, was approved in combination with carboplatin and etoposide for first-line treatment of extensive-stage SCLC. This approval was based on improved overall survival and progression-free survival compared to chemotherapy alone. Similarly, Durvalumab, another PD-L1 inhibitor, has been approved in combination with platinum-etoposide chemotherapy for extensive-stage SCLC, showing improved survival outcomes. These approvals highlight the role of immune checkpoint inhibitors in enhancing the efficacy of traditional chemotherapy in SCLC treatment.

What other types of research exist?

Promising novel alternatives for Small Cell Lung Cancer (SCLC) patients include: 1) Nivolumab (PD-1 inhibitor) combined with Ipilimumab (CTLA-4 inhibitor), which has shown improved overall survival in metastatic settings. 2) Atezolizumab (PD-L1 inhibitor) in combination with chemotherapy, which has been approved for extensive-stage SCLC. 3) Pembrolizumab (PD-1 inhibitor) as monotherapy or in combination with chemotherapy, which has shown efficacy in various solid tumors, including SCLC.

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Immunotherapy for Small Cell Lung Cancer (ADRIATIC Trial)

Phase 3

Waitlist Available

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

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

Must have

Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to randomization and the first dose of IP. Chemotherapy must contain platinum and IV etoposide. Radiotherapy must be either total 60-66 Gy over 6 weeks for the standard QD regimen or total 45 Gy over 3 weeks for hyperfractionated BD schedules

Have not progressed following definitive concurrent chemoradiation

Must not have

Uncontrolled intercurrent illness, including but not limited to interstitial lung disease

Active infection including tuberculosis, HIV, hepatitis B and C

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 6 years

Awards & highlights

Pivotal Trial

Summary

This trial is testing whether Durvalumab alone or with Tremelimumab can help patients with a specific type of lung cancer who have already had initial treatment. The drugs aim to boost the immune system to fight off any remaining cancer cells. Durvalumab and Tremelimumab are being studied together for their potential to improve cancer treatment outcomes.

Who is the study for?

This trial is for patients with limited-stage small cell lung cancer (stages I-III) who haven't worsened after chemoradiation. They must have completed a specific chemotherapy and radiotherapy regimen recently, be expected to live at least 12 weeks, and have an ECOG performance status of 0 or 1.

What is being tested?

The study tests Durvalumab alone or combined with Tremelimumab versus a placebo as additional treatment post-chemoradiation in phase III trials. It's randomized, double-blind, and includes multiple international centers.

What are the potential side effects?

Durvalumab and Tremelimumab can cause immune-related side effects like inflammation in various organs, fatigue, potential infections due to weakened immunity, skin reactions, hormonal changes, and infusion-related reactions.

Eligibility Criteria

Inclusion Criteria

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

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I've completed 4 cycles of specific chemo and radiotherapy recently.

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My condition has not worsened after receiving combined chemotherapy and radiation.

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

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My lung cancer is small cell type and not spread widely (stage I-III).

Exclusion Criteria

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

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I do not have any uncontrolled illnesses like lung disease.

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I do not have an active infection like TB, HIV, or hepatitis.

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I received chemotherapy and radiotherapy one after the other, with no overlap.

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My condition is extensive-stage small cell lung cancer.

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I have or had an autoimmune or inflammatory disorder.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 6 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 6 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 6 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Progression-free survival (PFS)

Secondary study objectives

Overall Survival (OS)

PD-L1 expression in tumor and/or immune cells relative to response/efficacy outcomes (PFS, OS & ORR).

Progression-free survival PFS

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

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Durvalumab + TremelimumabExperimental Treatment2 Interventions

Durvalumab in combination with tremelimumab: Durvalumab (1500 mg IV) q4w in combination with tremelimumab (75 mg IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with tremelimumab.

Group II: Durvalumab + PlaceboExperimental Treatment2 Interventions

Durvalumab monotherapy: Durvalumab (1500 mg intravenous \[IV\]) q4w in combination with placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with placebo saline solution.

Group III: Placebo + PlaceboPlacebo Group1 Intervention

Placebo: Placebo saline solution (IV) q4w in combination with a second placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by a single placebo saline solution q4w. The first placebo saline solution monotherapy dose q4w will be 4 weeks after the final dose of the 2 placebo saline solutions in combination.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Durvalumab

2017

Completed Phase 2

~3750

Tremelimumab

2017

Completed Phase 2

~3070

0 / 9Eligibility 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 Small Cell Lung Cancer (SCLC) include chemotherapy, radiation therapy, and immunotherapy. Chemotherapy works by targeting rapidly dividing cancer cells, while radiation therapy uses high-energy rays to kill cancer cells. Immunotherapy, such as Durvalumab (a PD-L1 inhibitor) and Tremelimumab (a CTLA-4 inhibitor), enhances the body's immune response against cancer cells. Durvalumab blocks the PD-L1 protein, preventing cancer cells from evading immune detection, while Tremelimumab inhibits CTLA-4, enhancing T-cell activation. These mechanisms are crucial for SCLC patients as they offer a targeted approach to boost the immune system's ability to fight cancer, potentially leading to improved survival rates and better management of the disease.

Durvalumab Plus Tremelimumab in Solid Tumors: A Systematic Review.Immunotherapy for LELC: Case Report and a Focused Review.Immunotherapy in extensive small cell lung cancer.