Atezolizumab Clinical Trials

What Is Atezolizumab?

Atezolizumab is an FDA-approved medication for adult patients with urothelial cancer, non-small cell lung cancer, extensive-stage small cell lung cancer, hepatocellular carcinoma, and triple-negative breast cancer. It is an immune checkpoint inhibitor, specifically a monoclonal antibody. Atezolizumab works by binding to the protein PD-L1 (programmed death-ligand 1) found on the surface of some cancer cells. By blocking PD-L1, atezolizumab prevents cancer cells from suppressing the immune system, allowing the body's immune cells to better recognize and attack the cancer. The U.S. Food and Drug Administration (FDA) granted accelerated approval to Atezolizumab in combination with nab-paclitaxel for unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1. It was also approved by the FDA in May 2016 for locally advanced or metastatic urothelial carcinoma.

Uses and Conditions Under Study

Atezolizumab is extensively studied for various cancer types, often as a monotherapy or in combination with other treatments. Clinical trials aim to understand its safety and effectiveness across different stages of disease and in various patient populations.

• Lung Cancers: Atezolizumab is being investigated for several lung conditions, including Non-Small Cell Lung Cancer (NSCLC), Small Cell Lung Cancer (SCLC), and malignant pleural mesothelioma. NSCLC is a common type of lung cancer, and atezolizumab's mechanism of action helps the immune system target these cells. There are 26 trials for Non-Small Cell Lung Cancer, 22 trials for Non-small Cell Lung Cancer, and 19 trials for Non Small Cell Lung Cancer, along with studies for NSCLC brain metastases.
• Breast Cancers: This drug is studied for breast cancer, particularly Triple Negative Breast Cancer (TNBC), which is often aggressive and lacks common therapeutic targets. Atezolizumab aims to boost the immune response against these tumors. There are 26 trials for Breast Cancer and 19 trials for Triple Negative Breast Cancer.
• Urogenital Cancers: Atezolizumab is a focus of research for cancers affecting the urinary system and reproductive organs. This includes Urothelial Carcinoma and Bladder Cancer, where it may improve outcomes for patients with advanced disease. Endometrial cancer and prostate cancer are also under investigation. There are 26 trials for Urothelial Carcinoma and 21 trials for Bladder Cancer.
• Liver Cancers: For Hepatocellular Carcinoma (HCC), a common type of liver cancer, atezolizumab is being studied alone and in combination with other agents like bevacizumab. This combination has become a standard first-line systemic treatment for unresectable HCC. There are 51 trials for Hepatocellular Carcinoma.
• Other Cancers: Atezolizumab is also being investigated for a range of other advanced cancers, including Colorectal Cancer (21 trials), Melanoma (18 trials), Glioblastoma, bile duct cancer, and Richter's Transformation. These studies explore its potential in different tumor types, sometimes in combination with radiation therapy or other targeted drugs.
• Idiopathic Pulmonary Fibrosis (IPF): Beyond cancer, atezolizumab is being evaluated in patients with IPF, a progressive scarring condition of the lung. This research aims to determine its safety and preliminary efficacy in stopping the progression of fibrosis.

Dosing

Atezolizumab is primarily administered as an intravenous (IV) infusion, meaning it is given directly into a vein. Some studies also explore subcutaneous (SC) administration, where the drug is injected under the skin. The standard fixed dose of 1,200 mg is typically given by intravenous infusion every 21 days for approved indications, following its prescribing information. However, various other dosages and administration schedules are being investigated in clinical trials.

For example, studies have explored different dose levels of atezolizumab ranging from 0.01 mg/kg to 20 mg/kg in dose-escalation phases. In combination therapies, atezolizumab has been studied at doses such as 420 mg or 840 mg when combined with other agents like gilteritinib. Other investigational forms include specific formulations like "Atezolizumab-G-lena 15mg" and "Atezolizumab-G-lena 20mg." The specific dose and schedule depend on the type of cancer, the combination therapy being used, and the stage of the clinical trial.

Side Effects

In clinical trials involving patients treated with Atezolizumab, the most frequently reported side effect was hair loss (alopecia). Across 4 trials with 1,658 patients receiving Atezolizumab, 57.1% experienced alopecia, compared to 59.4% of patients on placebo. Nausea was also common, affecting 42.8% of patients on Atezolizumab in these same 4 trials, similar to 42.9% on placebo.

Other common side effects reported in larger patient populations across multiple trials include:

• Anemia: 36.7% of 5,196 patients on Atezolizumab experienced anemia across 22 trials, which was the same rate as patients on placebo (36.7%).
• Diarrhea: 28.8% of 5,196 patients on Atezolizumab reported diarrhea across 22 trials, compared to 25.8% on placebo.
• Fatigue: 28.3% of 3,538 patients on Atezolizumab experienced fatigue across 18 trials, compared to 25.0% on placebo.
• Decreased appetite: 21.1% of 3,265 patients on Atezolizumab reported decreased appetite across 15 trials, compared to 17.7% on placebo.
• Vomiting: 19.9% of 3,288 patients on Atezolizumab experienced vomiting across 17 trials, compared to 19.0% on placebo.

Clinical Trial Results

Non-Small Cell Lung Cancer (NSCLC)

In two studies comparing Atezolizumab to docetaxel in patients with locally advanced or metastatic NSCLC who had previously failed platinum therapy, Atezolizumab demonstrated improved overall survival and duration of response.

In a randomized Phase 2 study (NCT01903993), patients treated with Atezolizumab had a median overall survival of 12.6 months, compared to 9.7 months for those on docetaxel. The median duration of response was also longer with Atezolizumab at 18.6 months, versus 7.2 months for docetaxel. The objective response rate was 15.3% for Atezolizumab and 14.7% for docetaxel.

Another study (NCT02008227) showed similar results. The median overall survival for patients on Atezolizumab was 13.8 months, compared to 9.6 months for docetaxel. The median duration of response was 16.3 months for Atezolizumab, versus 6.2 months for docetaxel. Additionally, 63.8% of patients on Atezolizumab died during the study period, compared to 70.1% on docetaxel.

In studies of Atezolizumab monotherapy for PD-L1 positive locally advanced or metastatic NSCLC:

A study (NCT01846416) involving first-line (1L) participants showed a median overall survival of 14.4 months. For participants who had received two or more prior lines of therapy (2L+), the median duration of objective response was 17.0 months. The objective response rate for 1L participants was 29%.

Another study (NCT02031458) in first-line patients reported a median overall survival of 14.0 months. The duration of response, as assessed by an independent review facility, was 8.5 months. The objective response rate in this first-line cohort was 21.1%.

Renal Cell Carcinoma (RCC)

In a study (NCT01984242) of untreated advanced RCC, Atezolizumab was evaluated alone or in combination with bevacizumab, compared to sunitinib.

In a specific patient population (IC1/2/3), the median overall survival was 30.2 months for Atezolizumab alone and 27.3 months for Atezolizumab combined with bevacizumab. The duration of response for the combination of Atezolizumab and bevacizumab was 22.4 months, compared to 14.1 months for sunitinib in this population.

The objective response rate in the IC1/2/3 population was 25.9% for Atezolizumab, 48.0% for Atezolizumab with bevacizumab, and 28.3% for sunitinib. Progression-free survival (PFS) in the overall study population was 6.1 months for Atezolizumab, 11.7 months for Atezolizumab with bevacizumab, and 8.4 months for sunitinib.

Currently Recruiting Trials

Atezolizumab is currently being investigated in numerous clinical trials to explore its potential in treating a wide range of cancers, often in combination with other therapies. These studies aim to improve outcomes for patients with various advanced or recurrent conditions.

• A Phase 4 trial sponsored by the Icahn School of Medicine at Mount Sinai (NCT07059494) is evaluating atezolizumab and bevacizumab in combination with Y^90 radioembolization for hepatocellular carcinoma (HCC) in patients considered for liver transplant. This feasibility study aims to enroll **40 participants**, including those beyond or within Milan Criteria with high AFP levels.
• Boehringer Ingelheim is sponsoring a large Phase 3 study (NCT07472517) called DAREON ® -Lung-1. This trial compares obrixtamig plus atezolizumab, carboplatin, and etoposide to standard chemotherapy in adults with advanced small cell lung cancer (SCLC), targeting an enrollment of **670 participants**.
• For patients with relapsed osteosarcoma, Emory University is conducting a Phase 1 dose escalation study (NCT06492954) to determine the safety and tolerability of atezolizumab combined with stereotactic body radiation therapy (SBRT) and surgery. This trial plans to enroll **12 participants**.
• MediLink Therapeutics (Suzhou) Co., Ltd. is exploring YL201 in combination with atezolizumab in a Phase 1/2 study (NCT07407933) for patients with advanced solid tumors, including extensive-stage SCLC. The study aims to enroll **118 participants** to assess safety and tolerability at different dosages.
• A Phase 2 study (NCT07235293) sponsored by Kahr Bio Australia Pty Ltd is comparing DSP107 in combination with atezolizumab against fruquintinib for advanced colorectal cancer. This trial seeks to enroll **90 participants**.
• The European Institute of Oncology is conducting a Phase 2 trial (NCT06690840) to evaluate atezolizumab and chemotherapy (cyclophosphamide and vinorelbine) as T-cell activators in metastatic triple negative breast cancer patients, with an enrollment target of **45 participants**.
• A Phase 1 study by the National Cancer Institute (NCI) (NCT06066138) is investigating therapeutic drug monitoring-based atezolizumab dosing in various locally advanced or metastatic cancers, including alveolar soft part sarcoma, non-small cell lung cancer, SCLC, HCC, and melanoma. This study aims to enroll **30 participants**.
• Cancer Research UK is sponsoring the DETERMINE Trial Treatment Arm 02 (NCT05770102), a Phase 2/3 study of atezolizumab monotherapy in adult, pediatric, and teenage/young adult patients with cancers characterized by high tumor mutational burden or microsatellite instability-high status. This arm plans to enroll **30 participants**.
• UNC Lineberger Comprehensive Cancer Center is conducting a Phase 1 study (NCT05542407) of ONC201 and atezolizumab in obesity-driven endometrial cancer, with an enrollment target of **58 participants**.

Where to Participate

Clinical trials for Atezolizumab are actively recruiting across a broad geographic area, offering opportunities for participation in many regions. Studies are currently underway in over **746 cities** across **51 states**, with a total of **1565 sites** globally. The leading locations for these trials include Houston, New York, Chicago, Pittsburgh, St Louis, Atlanta, and Boston.

Eligibility for these trials is inclusive, welcoming participants aged **6 to 120 years**, of all genders. Depending on the specific study, both healthy volunteers and children may be eligible to participate, contributing to the diverse research efforts for Atezolizumab.

Development Timeline

The clinical development of Atezolizumab began with its first trial on **October 29, 2008**, marking the start of an extensive research journey. Since then, a total of **746 trials** have been initiated, enrolling over **150,374 participants** worldwide.

Hoffmann-La Roche has been a primary driver of this development, sponsoring **163 trials**, with significant contributions also coming from the National Cancer Institute (NCI) and Genentech, Inc. The research pipeline has seen substantial activity across all phases, with **323 Phase 2 trials** and **138 Phase 1 trials** exploring new indications and combinations. There are also **106 Phase 3 trials** underway, aiming to confirm efficacy and safety on a larger scale.

Initially investigated for conditions like IBS-C and hyperphosphatemia, the focus quickly expanded to a wide array of cancers. Atezolizumab is now being studied for its potential in treating various solid tumors, including breast cancer, urothelial carcinoma, non-small cell lung cancer, colorectal cancer, bladder cancer, triple negative breast cancer, melanoma, renal cell carcinoma, hepatocellular carcinoma, and small cell lung cancer, among many others. This broad exploration highlights the ongoing commitment to understanding and expanding the therapeutic benefits of Atezolizumab for patients with diverse cancer types.