Atezolizumab for Lung Cancer

Overseen By Sandy Tran

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Southern California

Must not be taking: Antivirals, Immunosuppressants, Immunostimulants

Disqualifiers: Autoimmune disease, Brain metastases, Cardiovascular, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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: 3

Duration: 1-2 years

37 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests whether subcutaneous atezolizumab can be effectively given at home with medical care provided primarily using telemedicine in patients with non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This study may help determine if a telemedicine based approach that gives atezolizumab at home using a version of the drug designed for subcutaneous injection under the skin is safe and feasible.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients on stable pain medication regimens and those on certain immunosuppressive or antiviral therapies may have restrictions. It's best to discuss your specific medications with the trial team.

What data supports the idea that Atezolizumab for Lung Cancer is an effective drug?

The available research does not provide any data on Atezolizumab for Lung Cancer. Instead, it focuses on a different drug, tocilizumab, which is used for treating rheumatoid arthritis. Therefore, there is no information here to support the effectiveness of Atezolizumab for Lung Cancer. ^{1 2 3 4 5}

Is atezolizumab safe for humans?

Atezolizumab, also known as Tecentriq, has been shown to have an acceptable safety profile in clinical trials for lung cancer. Common side effects include fatigue, decreased appetite, and nausea, while more serious side effects can include pneumonia and liver inflammation. It is generally well tolerated, but like all medications, it can cause side effects in some people. ^{5 6 7 8 9}

What makes the drug Atezolizumab with Recombinant Human Hyaluronidase unique for lung cancer treatment?

Atezolizumab combined with Recombinant Human Hyaluronidase is unique because it may allow for subcutaneous (under the skin) administration, which can be more convenient compared to traditional intravenous (into the vein) methods, potentially improving patient comfort and adherence. ^{2 5 10 11 12}

Research Team

Jorge J. Nieva

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for adults with non-small cell lung cancer who can receive atezolizumab, have high PD-L1 expression without certain genetic mutations, and a life expectancy of at least 3 months. They must be able to follow the study plan, use contraception if necessary, and have access to wifi or data for telemedicine. Exclusions include recent significant cardiovascular issues, other cancers within 3 years (with some exceptions), severe infections recently, pregnancy/breastfeeding intentions soon, uncontrolled symptoms related to cancer or autoimmune diseases.

Inclusion Criteria

Your white blood cell count is normal without needing extra medication to support it.

My liver and bone enzymes are within acceptable levels, even with my cancer spread.

Your platelet count is at least 100,000 per microliter without needing a blood transfusion.

Exclusion Criteria

I have a history of lung conditions or signs of lung inflammation.

I haven't had major heart problems in the last 3 months.

I have had cancer spread to the lining of my brain and spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous atezolizumab and recombinant human hyaluronidase every 3 weeks at home, administered by a healthcare provider

1-2 years

Home visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atezolizumab and Recombinant Human Hyaluronidase

Trial Overview The trial tests subcutaneous atezolizumab administered at home with telemedicine support in patients with non-small cell lung cancer. It aims to see if this method is safe and workable. Atezolizumab is an immunotherapy drug that may boost the immune system's ability to fight cancer by interfering with tumor growth.

Participant Groups

Group I: Treatment (atezolizumab and recombinant human hyaluronidase) Experimental Treatment 2 Interventions

Patients receive atezolizumab and recombinant human hyaluronidase SC over 3-8 minutes on day 1. Cycles repeat every 3 weeks for 1 year (early-stage lung cancer) or up to 2 years (late-stage lung cancer) in the absence of disease progression or unacceptable toxicity.

Atezolizumab and Recombinant Human Hyaluronidase is already approved in European Union, United States for the following indications:

Approved in European Union as Tecentriq for:

• Urothelial carcinoma
• Non-small cell lung cancer
• Small cell lung cancer
• Hepatocellular carcinoma
• Alveolar soft part sarcoma

Approved in United States as Tecentriq for:

• Non-small cell lung cancer
• Small cell lung cancer
• Hepatocellular carcinoma
• Melanoma
• Alveolar soft part sarcoma

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 45 rheumatoid arthritis patients who did not respond adequately to TNF inhibitors, switching to tocilizumab (TCZ) significantly improved disease activity scores from 5.87 to 2.94 after 52 weeks (P < 0.0001).

TCZ also reduced joint damage progression, with a mean change in the Sharp score of 1.20 after treatment, and improved the rate of radiographic non-progression to 66.7%, indicating its efficacy in preventing joint destruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of interleukin-6 receptor inhibitor, tocilizumab, in preventing joint destruction in patients with rheumatoid arthritis showing inadequate response to TNF inhibitors. Tanaka, Y., Takeuchi, T., Amano, K., et al.[2016]

In a study of 693 rheumatoid arthritis patients over 3 years, tocilizumab (TCZ) demonstrated significant clinical efficacy, with a decrease in disease activity score (DAS28-ESR) from 5.1 to 2.2, and an increase in remission rates from 0.9% to 32.2%.

TCZ effectively prevented joint damage, with structural remission rates improving from 68.8% in the first year to 88.9% by the third year, indicating its strong protective effect against bone destruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and structural remission rates increased annually and radiographic progression was continuously inhibited during a 3-year administration of tocilizumab in patients with rheumatoid arthritis: A multi-center, prospective cohort study by the Michinoku Tocilizumab Study Group. Hirabayashi, Y., Munakata, Y., Miyata, M., et al.[2018]

In a study of 322 rheumatoid arthritis patients treated with tocilizumab (TCZ), 57.5% achieved low disease activity and 38.1% reached disease remission after 6 months, indicating TCZ's effectiveness in managing RA symptoms.

The safety profile of TCZ was generally good, with 28.6% of patients experiencing drug-related adverse events, primarily mild issues like hypercholesterolemia and leucopenia, and only 7.5% discontinuing treatment due to safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab in the treatment of patients with rheumatoid arthritis in real clinical practice: results of an Italian observational study. Caporali, R., Idolazzi, L., Bombardieri, S., et al.[2018]

Tocilizumab, when combined with disease-modifying anti-rheumatic drugs (DMARDs), significantly improved symptoms of rheumatoid arthritis in patients who had not responded adequately to DMARDs, with higher response rates (ACR20: 69.8% vs 24.6%, ACR50: 38.8% vs 10.1%, ACR70: 12.9% vs 2.9%) compared to placebo over a 24-week period.

The treatment was generally safe, with most adverse events being mild to moderate, although a higher percentage of patients in the tocilizumab group experienced infections and liver enzyme increases; however, serious adverse events were low (0.7% in tocilizumab vs 5.9% in placebo).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy and safety of tocilizumab combined with disease-modifying anti-rheumatoid drugs in the treatment of active rheumatoid arthritis: a multi-center, randomized, double-blinded, placebo-controlled trial]. Shi, Q., Zhao, Y., Bao, CD., et al.[2016]

In a study involving 48 healthy volunteers, the combination of tocilizumab with rHuPH20 slightly increased the drug's exposure levels compared to tocilizumab alone, indicating a potential enhancement in its pharmacokinetics.

The combination treatment was well tolerated, and the pharmacodynamic effects on inflammatory markers were similar whether rHuPH20 was included or not, suggesting that the addition of rHuPH20 does not compromise safety or efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of single subcutaneous doses of tocilizumab administered with or without rHuPH20. Morcos, PN., Zhang, X., McIntyre, C., et al.[2016]

Atezolizumab administered subcutaneously (SC) showed noninferior drug exposure compared to intravenous (IV) administration in patients with non-small-cell lung cancer, indicating that SC could be a viable alternative to IV treatment.

Both SC and IV forms of atezolizumab demonstrated similar efficacy, safety, and immunogenicity profiles, with no new safety concerns identified, supporting the use of SC for improved treatment convenience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications. Burotto, M., Zvirbule, Z., Mochalova, A., et al.[2023]

Subcutaneous (SC) atezolizumab, when administered at doses of 1800 mg every 3 weeks or 1200 mg every 2 weeks, achieved serum levels comparable to the intravenous (IV) formulation, indicating its potential as an effective alternative for patients with non-small cell lung cancer.

The SC formulation was well tolerated and exhibited a safety profile similar to the established IV version, although absorption was slightly lower when injected in the abdomen compared to the thigh, suggesting that injection site may influence drug delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Dose-Finding Phase 1b Study of Subcutaneous Atezolizumab in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer. Felip, E., Burotto, M., Zvirbule, Z., 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, a monoclonal antibody targeting PD-L1, has shown significant improvements in progression-free and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) when combined with chemotherapy, as demonstrated in the IMpower studies.

The safety profile of atezolizumab in combination with chemotherapy is acceptable, with common immune-related adverse events including rash (18-28%), hypothyroidism (8-15%), and hepatitis (5-17%), consistent with its known effects as a single agent, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. Manzo, A., Carillio, G., Montanino, A., et al.[2022]

In a study involving 7901 patients with rheumatoid arthritis, tocilizumab (TCZ) demonstrated a safety profile with a 43.9% rate of total adverse events and a 9.6% rate of serious adverse events, primarily infections (3.8%).

The effectiveness of TCZ was confirmed, with 47.6% of patients achieving remission by Week 28, and factors such as lower disease severity and absence of prior biologic treatments were associated with better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of tocilizumab: postmarketing surveillance of 7901 patients with rheumatoid arthritis in Japan. Koike, T., Harigai, M., Inokuma, S., et al.[2016]

Eculizumab is a humanized monoclonal antibody that inhibits the cleavage of complement component C5, showing potential as a treatment for chronic inflammatory diseases like rheumatoid arthritis and nephritis, with ongoing phase II trials since 2002.

The drug has received Orphan Drug status from the FDA for conditions such as dermatomyositis and membranous nephritis, indicating its promise in treating rare diseases, while analysts predict significant sales growth in the coming years for its various indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eculizumab (Alexion). Kaplan, M.[2005]

In a study involving 4009 patients treated with tocilizumab for an average of 4 years, the overall malignancy rate was found to be stable and consistent with what is expected in patients with rheumatoid arthritis (RA).

The standardized incidence ratios (SIRs) indicated that the risk of developing malignancies, particularly lung, prostate, and non-Hodgkin lymphoma, was higher compared to the general population, but these rates align with the known risks associated with RA itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Malignancy rates in patients with rheumatoid arthritis treated with tocilizumab. Rubbert-Roth, A., Sebba, A., Brockwell, L., et al.[2022]

References

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

Effect of interleukin-6 receptor inhibitor, tocilizumab, in preventing joint destruction in patients with rheumatoid arthritis showing inadequate response to TNF inhibitors. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Clinical and structural remission rates increased annually and radiographic progression was continuously inhibited during a 3-year administration of tocilizumab in patients with rheumatoid arthritis: A multi-center, prospective cohort study by the Michinoku Tocilizumab Study Group. [2018]

3. Italy pubmed.ncbi.nlm.nih.gov

Tocilizumab in the treatment of patients with rheumatoid arthritis in real clinical practice: results of an Italian observational study. [2018]

4. China pubmed.ncbi.nlm.nih.gov

[The efficacy and safety of tocilizumab combined with disease-modifying anti-rheumatoid drugs in the treatment of active rheumatoid arthritis: a multi-center, randomized, double-blinded, placebo-controlled trial]. [2016]

5. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of single subcutaneous doses of tocilizumab administered with or without rHuPH20. [2016]

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

IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications. [2023]

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

Results of a Dose-Finding Phase 1b Study of Subcutaneous Atezolizumab in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer. [2022]

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

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

9. England pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. [2022]

10. Canada pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of tocilizumab: postmarketing surveillance of 7901 patients with rheumatoid arthritis in Japan. [2016]

11. England pubmed.ncbi.nlm.nih.gov

Eculizumab (Alexion). [2005]

12. England pubmed.ncbi.nlm.nih.gov

Malignancy rates in patients with rheumatoid arthritis treated with tocilizumab. [2022]