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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug atezolizumab, administered via a simple under-the-skin injection, can be safely and effectively given at home to help treat non-small cell lung cancer. Atezolizumab, a type of immunotherapy, boosts the immune system to better attack cancer cells. The trial aims to determine if telemedicine can practically monitor patients at home. Individuals with non-small cell lung cancer who have experienced disease progression on certain treatments and have reliable internet access might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of atezolizumab and recombinant human hyaluronidase, known as Tecentriq Hybreza, is generally safe for patients. This combination offers flexibility while maintaining safety in treating certain types of cancer.

Data collection is ongoing for using this treatment under the skin for non-small cell lung cancer. However, the intravenous (IV) form of atezolizumab has been well-studied and approved by the FDA for similar conditions. Common side effects reported in these studies include fatigue, nausea, and loss of appetite, though serious reactions are rare.

The trial available for participation tests a new method of administering this treatment at home, with close safety monitoring. Existing research suggests that many patients tolerate the treatment well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about atezolizumab combined with recombinant human hyaluronidase for lung cancer because it introduces a new delivery method that enhances treatment convenience. Unlike traditional intravenous treatments, this combination is administered subcutaneously (under the skin) in just 3-8 minutes, potentially improving patient comfort and reducing time spent in clinics. Additionally, atezolizumab is an immune checkpoint inhibitor that helps the immune system attack cancer cells more effectively, offering a promising therapeutic approach for both early and late-stage lung cancer. This unique delivery and mechanism of action make it a standout option compared to the existing standard treatments like chemotherapy and other immunotherapies.

What evidence suggests that atezolizumab might be an effective treatment for lung cancer?

Research has shown that atezolizumab can extend the lives of people with advanced or spreading non-small cell lung cancer (NSCLC). This treatment is effective and has manageable side effects. In this trial, participants will receive atezolizumab as a subcutaneous injection, along with recombinant human hyaluronidase. Studies have found that this method works as well as the traditional IV administration, maintaining the drug's effectiveness. Overall, strong evidence indicates that atezolizumab helps the immune system combat lung cancer cells. ^{3 4 5 6 7}

Who Is on the Research Team?

Jorge J. Nieva

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9716834/

updated long-term efficacy of atezolizumab in a diverse ... In patients with previously treated advanced or metastatic non-small cell lung cancer (NSCLC), atezolizumab therapy improves survival with manageable safety.

2. aetna.com aetna.com/cpb/medical/data/900_999/0909.html

Atezolizumab (Tecentriq) and Atezolizumab and ... Investigators evaluated the efficacy and safety of atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) in adult patients with locally advanced or metastatic ...

3. tecentriq.com tecentriq.com/hybreza/results/how-tecentriq-hybreza-may-help.html

Effectiveness & Safety of TECENTRIQ HYBREZA™ ... TECENTRIQ HYBREZA injections was observed to be similarly effective in fighting cancer as TECENTRIQ infusions.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05340309

NCT05340309 | Subcutaneous Atezolizumab for the ... 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) ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8518371/

Results of a Dose‐Finding Phase 1b Study of Subcutaneous ... A 2-part, open-label, global, multicenter, phase 1b/3 study, is evaluating the pharmacokinetics (PK), safety, and efficacy of SC atezolizumab.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/761347s000lbl.pdf

highlights of prescribing information - accessdata.fda.gov Below is a description of adverse reactions of intravenous atezolizumab in these adequate and well-controlled NSCLC studies. Non-Small Cell Lung Cancer (NSCLC).

7. roche.com roche.com/media/releases/med-cor-2024-09-13

FDA approves Roche's Tecentriq Hybreza, the first and ... Tecentriq Hybreza provides patients and physicians with greater flexibility of treatment options while showing safety and efficacy ...