Durvalumab Clinical Trials

What Is Durvalumab?

Durvalumab is an FDA-approved medication for lung cancer. It is an immunotherapy drug that works by stimulating the immune system to fight cancer. Specifically, durvalumab is an anti-programmed death-ligand 1 (anti-PD-L1) antibody, which belongs to a class of drugs known as checkpoint inhibitors. These agents help the body's immune cells recognize and attack cancer cells more effectively by blocking signals that cancer cells use to evade the immune system.

While approved for lung cancer, durvalumab is also being investigated for its potential to treat various other advanced solid cancers, either alone or in combination with other therapies. Studies are exploring its use in different cancer types, aiming to improve treatment outcomes and patient survival.

Uses and Conditions Under Study

Durvalumab is being studied across a wide range of cancers, often in combination with other treatments like chemotherapy, radiation, or other immunotherapies. A total of 732 trials have investigated durvalumab, enrolling 112,828 participants since the first trial began in 2010.

• Lung Cancers: Durvalumab is extensively studied for various lung cancers, including Non-small Cell Lung Cancer (NSCLC) in 26 trials, Lung Cancer in 22 trials, and Small Cell Lung Cancer (SCLC). NSCLC is the most common type of lung cancer, and durvalumab, as an immunotherapy, aims to improve outcomes by enhancing the immune response against these tumors, particularly in advanced or unresectable stages.
• Liver Cancers: Hepatocellular Carcinoma (HCC), a common type of liver cancer, is being investigated in 37 trials. Durvalumab, often combined with tremelimumab (known as the STRIDE regimen), is an approved first-line therapy for unresectable HCC, and ongoing studies explore its efficacy with radiation therapy or other agents to improve response rates.
• Gastrointestinal and Biliary Cancers: Durvalumab is studied in Biliary Tract Cancer (15 trials) and Colorectal Cancer (14 trials). These studies often combine durvalumab with chemotherapy or other targeted agents to address these aggressive cancers, which typically have poor prognoses.
• Breast and Bladder Cancers: Breast Cancer is investigated in 22 trials, including triple-negative breast cancer (TNBC) and HER2-positive or HER2-low inflammatory breast cancer. For Bladder Cancer (15 trials), durvalumab is being tested in combination with other drugs, sometimes before surgery for muscle-invasive bladder cancer.
• Other Solid Tumors: Durvalumab is also under investigation for other malignant solid tumors, including sarcomas and glioblastoma multiforme, often as part of combination therapies to explore new treatment strategies and improve patient outcomes.

Dosing

Durvalumab is primarily administered as an intravenous (IV) infusion. The most commonly studied dose is 1,500 mg, typically given once every 4 weeks (Q4W) or once every 3 weeks (Q3W) when combined with platinum doublet chemotherapy. For instance, in some preoperative treatment phases, patients receive 1,500 mg of durvalumab every second two-week cycle (Q4W) alongside chemotherapy.

Other investigational dosing strategies include different milligram-per-kilogram (mg/kg) doses, such as 3 mg/kg, 10 mg/kg, or 20 mg/kg, often in combination with other agents like tremelimumab. Some studies also explore subcutaneous (SC) formulations of durvalumab at various dose levels. While specific pediatric doses are not detailed in the provided data, these trials focus on adult patients with various cancers.

Side Effects

Clinical trials have identified several side effects associated with Durvalumab. The following are some of the most commonly reported adverse events, comparing the rates in patients receiving Durvalumab to those receiving a placebo, based on data from trials involving thousands of participants.

• Anemia (low red blood cell count) occurred in 37.4% of patients taking Durvalumab, compared to 31.9% on placebo.
• Nausea was experienced by 33.1% of patients on Durvalumab, while 31.3% of patients on placebo reported it.
• Neutropenia (low neutrophil count) affected 22.3% of patients receiving Durvalumab, versus 18.4% on placebo.
• Constipation was reported in 18.5% of patients taking Durvalumab, compared to 20.8% on placebo.
• Diarrhea occurred in 18.4% of patients on Durvalumab, versus 19.5% on placebo.
• Fatigue was seen in 16.6% of patients on Durvalumab, compared to 16.9% on placebo.
• Hypothyroidism (underactive thyroid) was observed in 11.2% of patients taking Durvalumab, significantly higher than the 5.4% on placebo.

Clinical Trial Results

The efficacy of Durvalumab has been evaluated in several clinical trials across various cancer types, both as a single agent and in combination with other therapies.

Durvalumab with Tremelimumab (NCT01975831)

• In a Phase 1 study combining Durvalumab and tremelimumab, the median overall survival varied by cancer type and dose. For patients receiving 3 mg/kg Durvalumab and 3 mg/kg tremelimumab, the median overall survival was 664 days.
• In the expansion cohorts, patients with cervical cancer had a median overall survival of 583 days, while those with ovarian cancer and renal cell carcinoma had median overall survival of 460 days and 462 days, respectively.
• For patients with renal cell carcinoma, the median progression-free survival was 326 days based on immune-related response criteria (irRC) and 279 days based on RECIST 1.1 criteria.
• The objective response rate (complete or partial response) in the renal cell carcinoma expansion cohort was 66.7% (10 out of 15 participants) based on RECIST 1.1.

Durvalumab with MEDI0680 (NCT02118337)

• A Phase 1/2 study investigated Durvalumab in combination with MEDI0680 for advanced malignancies. In the dose-expansion phase, the combination of 20 mg/kg MEDI0680 and 750 mg Durvalumab showed an objective response rate (ORR) of 16.7%. This was compared to 23.8% for nivolumab monotherapy.
• The median progression-free survival for the combination was 3.6 months, which was similar to nivolumab monotherapy (3.6 months).
• For patients with PD-L1 positive status, the combination of MEDI0680 and Durvalumab achieved an ORR of 40.0%, compared to 13.5% for PD-L1 negative patients.

Durvalumab with MEDI6469 (NCT02205333)

• In a Phase 1b/2 study, Durvalumab was evaluated in combination with MEDI6469. For patients receiving 2 mg/kg MEDI6469 and 3 mg/kg Durvalumab, the median overall survival was 11.2 months.
• The median progression-free survival for this combination was 5.6 months.
• The objective response rate for this specific combination was 16.7%.

Durvalumab with Oral Azacitidine for Myelodysplastic Syndromes (NCT02281084)

• In a study for myelodysplastic syndromes, the combination of oral azacitidine and Durvalumab was compared to oral azacitidine alone.
• For patients with progressive disease at baseline, the median overall survival was 14.56 months with the combination, significantly longer than 6.28 months with oral azacitidine alone.
• Similarly, for this group, the median progression-free survival was 12.10 months with the combination, compared to 6.28 months with oral azacitidine alone.
• In patients with stable disease at baseline, the combination achieved an overall response rate of 16.7%, compared to 6.3% with oral azacitidine alone. The median time to progression to acute myelogenous leukemia (AML) was 21.47 months for the combination in this cohort.

Currently Recruiting Trials

Where to Participate

• New York, New York (42 sites)
• Houston, Texas (39 sites)
• Atlanta, Georgia (39 sites)
• St Louis, Missouri (36 sites)
• Chicago, Illinois (34 sites)
• Baltimore, Maryland (32 sites)
• Pittsburgh, Pennsylvania (23 sites)
• Portland, Oregon (23 sites)
• Nashville, Tennessee (23 sites)
• Boston, Massachusetts (23 sites)

Development Timeline