Atezolizumab for Pulmonary Fibrosis

Overseen By Vivian Hwe

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Cedars-Sinai Medical Center

Must not be taking: Anticoagulants, Bronchodilators, Immunosuppressives, others

Disqualifiers: Asthma, Tuberculosis, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing atezolizumab, a medicine that boosts the immune system, in people aged 50 to 80 with idiopathic pulmonary fibrosis (IPF). IPF is a lung disease with no current treatments to stop its progression. Atezolizumab may help slow down lung damage by helping the immune system fight the disease.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications like cytotoxic or immunosuppressive drugs, cytokine modulating therapies, and some bronchodilators must not be used close to the screening period. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Atezolizumab for pulmonary fibrosis?

Atezolizumab has been shown to improve survival in patients with certain types of lung cancer, like non-small cell lung cancer, by targeting a protein that helps cancer cells hide from the immune system. However, its effectiveness specifically for pulmonary fibrosis is not directly supported by the available research. ^{1 2 3 4 5}

Is atezolizumab generally safe for humans?

Atezolizumab, also known as Tecentriq, has been used in various cancer treatments and generally has an acceptable safety profile, but it can cause side effects like fatigue, decreased appetite, and nausea. Serious side effects, though rare, can include immune-related issues like pneumonitis (lung inflammation), hepatitis (liver inflammation), and thyroid problems. There have been cases of severe reactions, including one fatal case involving pneumonitis and cardiac issues. ^{2 4 6 7 8}

How is the drug atezolizumab unique for treating pulmonary fibrosis?

Atezolizumab is unique because it is a monoclonal antibody that targets a specific protein (PD-L1) involved in the immune system, which is different from traditional treatments for pulmonary fibrosis that may not target the immune system in this way. It has been used in other conditions like lung cancer, showing potential benefits in survival, but its use in pulmonary fibrosis is novel and still under investigation. ^{1 2 5 7 9}

Research Team

Tanzira Zaman, MD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

This trial is for men and women over 50 with a confirmed diagnosis of idiopathic pulmonary fibrosis (IPF), as shown by specific patterns on high-resolution CT scans or lung biopsy. Participants must not have used certain IPF treatments recently, be free from significant other diseases, and agree to contraception if applicable. They cannot join if they've had recent vaccinations, blood clots, severe allergies to similar drugs, or are smokers.

Inclusion Criteria

You tested negative for hepatitis B surface antigen.

My lung biopsy shows UIP but my HRCT does not definitely confirm it.

You must have a specific pattern in your high-resolution CT scan of the lungs that shows a condition called UIP.

Exclusion Criteria

I am currently on medication for hepatitis B.

I had TB but completed treatment successfully.

I have had a blood clot in my leg or lung in the past 6 months or have had them more than once.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab 1200 mg IV every 3 weeks for 24 weeks

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atezolizumab

Trial Overview The study tests the safety and initial effectiveness of Atezolizumab—an immune checkpoint inhibitor already approved for cancer treatment—in patients with IPF. It aims to see how well this drug can work in a different disease by possibly using the body's own immune system to slow down fibrosis.

Participant Groups

Group I: Atezolizumab Experimental Treatment 1 Intervention

Atezolizumab 1200 mg IV every 3 weeks for 24 weeks

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

In a study of 17 patients with non-small cell lung cancer and interstitial pneumonia, atezolizumab showed a 1-year survival rate of 53.3%, indicating potential efficacy despite the high risk of severe side effects.

The incidence of pneumonitis was notably high at 29.4%, with 23.5% of cases being severe (grade ≥3), highlighting a significant safety concern for this treatment in patients with comorbid interstitial pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for Pretreated Non-Small Cell Lung Cancer with Idiopathic Interstitial Pneumonia: Final Analysis of Phase II AMBITIOUS Study. Ikeda, S., Kato, T., Kenmotsu, H., et al.[2022]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

Atezolizumab is the first approved anti-PD-L1 inhibitor for treating squamous cell lung cancer (SqCLC) in patients who have experienced disease progression after initial therapies, highlighting its role in advanced stages of non-small cell lung cancer (NSCLC).

Current research is exploring atezolizumab's effectiveness in various treatment settings for SqCLC, indicating its potential for broader applications in future clinical scenarios, although specific target agents for this cancer subtype remain limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti PD-L1 antibody: is there a histologic-oriented efficacy? Focus on atezolizumab in squamous cell non-small cell lung cancer. Gemelli, M., Bidoli, P., Colonese, F., et al.[2022]

Atezolizumab, an immune checkpoint inhibitor, is being tested in a phase II trial for its safety and efficacy in patients with advanced non-small cell lung cancer (NSCLC) who also have chronic fibrotic interstitial pneumonia, with a focus on a 1-year survival rate among 38 participants.

This study is significant as it aims to establish a treatment option for a patient group that currently lacks standard second-line therapies, potentially improving outcomes for those with both NSCLC and interstitial pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of atezolizumab for pretreated advanced/recurrent non-small cell lung cancer with idiopathic interstitial pneumonias: rationale and design for the TORG1936/AMBITIOUS study. Ikeda, S., Kato, T., Kenmotsu, H., et al.[2022]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

Atezolizumab (Tecentriq) is an FDA-approved treatment for unresectable or metastatic alveolar soft part sarcoma (ASPS), showing a 24% overall response rate in a clinical trial with 49 patients, and a durable response rate of 67% at 6 months and 42% at 12 months.

The treatment has a manageable safety profile, with common severe side effects including musculoskeletal pain (8%) and hypertension (6%), making it a viable option for patients with limited treatment alternatives for this high-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. Bergsma, EJ., Elgawly, M., Mancuso, D., et al.[2023]

Atezolizumab, an anti-PD-L1 antibody used for treating non-small cell lung cancer, can lead to severe immune-related adverse events (irAEs), including life-threatening conditions like pneumonitis, thrombocytopenia, and cardiac dysfunction.

In this case, while pneumonitis resolved with treatment, the other severe irAEs did not improve, ultimately leading to the patient's death, highlighting the critical need for effective management strategies for irAEs in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal outcome of atezolizumab in a patient with immune-mediated pneumonitis, thrombocytopenia, and cardiac dysfunction: A case report . Li, J., Deng, X., Wang, B., et al.[2020]

Atezolizumab monotherapy was associated with a high incidence of pneumonitis in patients with advanced or recurrent NSCLC and comorbid idiopathic interstitial pneumonia, leading to the early termination of the study.

Out of 17 enrolled patients, 29.4% experienced pneumonitis, with a notably higher risk (57.1%) in those with honeycomb lung, indicating that this patient population may be particularly vulnerable to immune checkpoint inhibitor-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Study of Atezolizumab for Pretreated NSCLC With Idiopathic Interstitial Pneumonitis. Ikeda, S., Kato, T., Kenmotsu, H., et al.[2023]

References

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

Atezolizumab for Pretreated Non-Small Cell Lung Cancer with Idiopathic Interstitial Pneumonia: Final Analysis of Phase II AMBITIOUS Study. [2022]

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

3. Singapore pubmed.ncbi.nlm.nih.gov

Anti PD-L1 antibody: is there a histologic-oriented efficacy? Focus on atezolizumab in squamous cell non-small cell lung cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A phase II study of atezolizumab for pretreated advanced/recurrent non-small cell lung cancer with idiopathic interstitial pneumonias: rationale and design for the TORG1936/AMBITIOUS study. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

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

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Fatal outcome of atezolizumab in a patient with immune-mediated pneumonitis, thrombocytopenia, and cardiac dysfunction: A case report . [2020]

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

A Phase 2 Study of Atezolizumab for Pretreated NSCLC With Idiopathic Interstitial Pneumonitis. [2023]