Atezolizumab + Radiation Therapy for Lung Cancer

Recruiting at 450 trial locations

Overseen By Luis Mariscal

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Immunosuppressive agents

Disqualifiers: Cardiovascular disease, Autoimmune disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 24 weeks

480 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial studies how well atezolizumab added to the usual radiation therapy works in treating patients with stage I-IIA 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. Radiation therapy, such as stereotactic body radiation therapy, uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving atezolizumab and radiation therapy may work better than radiation therapy alone in treating patients with early non-small cell lung cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not have received treatment with systemic immunostimulatory or immunosuppressive agents, including corticosteroids, within 14 days before joining the trial.

What data supports the effectiveness of the treatment Atezolizumab + Radiation Therapy for Lung Cancer?

Research shows that combining atezolizumab (an immune therapy drug) with stereotactic ablative radiotherapy (SABR) can lead to early positive responses in some lung cancer patients, and SABR using the CyberKnife system is effective for controlling lung tumors with minimal side effects. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Radiation Therapy safe for treating lung cancer?

The combination of Atezolizumab and stereotactic ablative radiotherapy (SABR) for lung cancer has been studied, and the treatment is generally well tolerated with the full dose of Atezolizumab being safe. SABR using CyberKnife has shown acceptable safety with manageable side effects in treating lung tumors. ^{2 3 4 6 7}

How does the treatment Atezolizumab + Radiation Therapy differ from other treatments for lung cancer?

This treatment combines atezolizumab, an immune-boosting drug, with stereotactic body radiation therapy (SABR), which precisely targets tumors with high doses of radiation. This combination aims to enhance the body's immune response against cancer cells, potentially improving outcomes for patients with early-stage non-small cell lung cancer who cannot undergo surgery. ^{2 5 8 9 10}

Research Team

Megan E Daly

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with early-stage non-small cell lung cancer (NSCLC) who haven't had previous treatment. Participants must be medically inoperable or unwilling to undergo surgery, have no significant heart disease, active hepatitis B/C or tuberculosis, and not be pregnant. They should not have received recent immunosuppressive treatments and must agree to use effective contraception.

Inclusion Criteria

I am 18 years old or older.

My liver tests are within the normal range.

I had my thyroid function tested within the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive atezolizumab IV every 21 days for 8 cycles and undergo SBRT for 3-8 treatments over 1-3 weeks

24 weeks

8 visits (in-person) for atezolizumab, multiple visits for SBRT

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Regular visits (in-person) for monitoring

Treatment Details

Interventions

• Atezolizumab
• Stereotactic Body Radiation Therapy

Trial Overview The study tests adding Atezolizumab, an immune system-boosting drug, to standard radiation therapy compared to radiation alone. The goal is to see if combining these treatments improves outcomes for patients with stage I-IIA NSCLC by helping the body's own immune system fight cancer more effectively.

Participant Groups

Group I: Arm A (atezolizumab, SBRT) Experimental Treatment 8 Interventions

Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Starting on day 1 cycle 3, patients also undergo SBRT for 3-8 treatments every 2 days or QD over 1-3 weeks. Patients undergo FDG-PET/CT during screening. Patients undergo blood sample collection and CT scans throughout the trial.

Group II: Arm B (SBRT) Active Control 7 Interventions

Beginning 21 days after randomization, patients undergo SBRT for 3-8 treatments every 2 days or QD over 1-3 weeks. Patients undergo FDG-PET/CT during screening. Patients undergo blood sample collection and CT scans throughout the trial.

Stereotactic Body Radiation Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Stereotactic Body Radiation Therapy for:

• Non-small cell lung cancer (NSCLC)
• Melanoma
• Renal cell carcinoma (RCC)
• Prostate cancer
• Oligoprogressive cancers

Approved in European Union as Stereotactic Body Radiation Therapy for:

• Non-small cell lung cancer (NSCLC)
• Melanoma
• Renal cell carcinoma (RCC)
• Prostate cancer
• Oligoprogressive cancers

Approved in Canada as Stereotactic Body Radiation Therapy for:

• Non-small cell lung cancer (NSCLC)
• Melanoma
• Renal cell carcinoma (RCC)
• Prostate cancer
• Oligoprogressive cancers

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 100 patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative body radiotherapy (SABR), the 1-, 2-, and 3-year local control rates were 100%, 93.55%, and 84.33%, respectively, indicating high efficacy in tumor control.

The treatment was associated with low toxicity, with only 2% of patients experiencing Grade-3 side effects, suggesting that SABR is a safe option for patients who are inoperable or refuse surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting. Heal, C., Ding, W., Lamond, J., et al.[2020]

In a phase I study involving 20 patients with early-stage non-small cell lung cancer, the combination of stereotactic ablative radiotherapy (SABR) and the immune-checkpoint inhibitor atezolizumab was well tolerated, with the maximum tolerated dose established at 1200 mg.

Early efficacy signals were observed, with 17% of patients showing responses after two cycles of atezolizumab before starting SABR, and specific biomarkers indicating T cell activation were found to be predictive of treatment benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. Monjazeb, AM., Daly, ME., Luxardi, G., et al.[2023]

Stereotactic ablative radiotherapy (SABR) using Cyberknife demonstrated high effectiveness in treating stage I non-small-cell lung cancer, with 2-year local control, progression-free, and overall survival rates of 91.9%, 61.7%, and 84.8%, respectively, based on a study of 153 patients.

The treatment was generally safe, with only 8.1% of patients experiencing severe toxicities, including one case of grade 5 radiation pneumonitis, indicating that while SABR is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. Hayashi, K., Suzuki, O., Shiomi, H., et al.[2022]

Stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage non-small cell lung cancer, especially for patients who cannot undergo surgery, showing high local tumor control rates with manageable side effects.

The CyberKnife system is particularly advantageous for SABR in lung tumors due to its ability to accurately target moving tumors during breathing, enhancing treatment precision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CyberKnife stereotactic ablative radiotherapy for lung tumors. Gibbs, IC., Loo, BW.[2022]

In a pilot study involving 12 patients with metastatic non-small cell lung cancer, the combination of hypofractionated image-guided radiation therapy (HIGRT) and atezolizumab achieved a disease control rate of 50%, with a partial response in 3 patients.

The treatment was associated with a median overall survival of 6.9 months and a median progression-free survival of 2.3 months, with the incidence of grade 3 adverse events being similar to that of atezolizumab alone, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of Atezolizumab Plus Hypofractionated Image Guided Radiation Therapy for the Treatment of Advanced Non-Small Cell Lung Cancer. Qin, A., Rengan, R., Lee, S., et al.[2021]

In a study of 106 patients with early-stage non-small cell lung cancer treated with CyberKnife® SBRT, the treatment demonstrated an 88% local control rate at 2 years, indicating its efficacy in managing this type of cancer.

The treatment was associated with low toxicity, with only 20% of patients experiencing mild fatigue and 17% mild dyspnea, and only 4% experiencing significant late effects, suggesting it is a safe option for medically inoperable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer. Temming, S., Kocher, M., Stoelben, E., et al.[2022]

Stereotactic ablative radiation therapy (SABR) for lung oligometastases shows promising safety and efficacy, with a 24-month overall survival rate of 74.6% and minimal toxicity, as only one significant adverse event was reported among 77 patients studied over an average follow-up of 22 months.

Colorectal metastases exhibited a notably higher local failure rate compared to other types of tumors, suggesting they may be more resistant to SABR, indicating a need for potential dose escalation strategies for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy. Binkley, MS., Trakul, N., Jacobs, LR., et al.[2022]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

Atezolizumab, a PD-L1 blocking antibody, shows higher rates of objective response, progression-free survival, and overall survival when used as a first-line therapy in chemotherapy-naïve patients with metastatic non-small cell lung cancer (NSCLC), compared to its use in later treatment lines.

The review included 15 ongoing studies, with 5 reporting results, indicating that atezolizumab is being explored in various treatment combinations and settings, suggesting its potential as a versatile first-line treatment option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. Ryu, R., Ward, KE.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting. [2020]

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

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. [2023]

3. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [2022]

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

CyberKnife stereotactic ablative radiotherapy for lung tumors. [2022]

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

A Pilot Study of Atezolizumab Plus Hypofractionated Image Guided Radiation Therapy for the Treatment of Advanced Non-Small Cell Lung Cancer. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer. [2022]

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

Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]

9. Spain pubmed.ncbi.nlm.nih.gov

Immune mediated colitis caused by lung cancer treatment with atezolizumab. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. [2023]