Atezolizumab + Radiation Therapy for Lung Cancer

Not currently recruiting at 459 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding atezolizumab, an immunotherapy drug, to radiation therapy improves treatment for early-stage non-small cell lung cancer compared to radiation alone. Atezolizumab boosts the immune system to fight cancer cells, while radiation precisely targets and destroys tumors. The trial includes individuals with stage I-IIA non-small cell lung cancer who have not received other treatments for this cancer and have specific tumor characteristics, such as a tumor size of 2 cm or more. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking advancements in cancer treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining atezolizumab with stereotactic body radiation therapy (SBRT) is generally safe for patients. In one study, this combination treatment proved practical and showed promising results. Most side effects were mild, though some patients experienced more serious reactions. Specifically, three patients had severe side effects, which were serious but not life-threatening. Common issues included a drop in white blood cells and nausea.

Overall, the treatment appears well-tolerated, with manageable side effects. Patients should discuss any concerns with a doctor, who can provide advice tailored to their health condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Researchers are excited about these treatments because they offer a potential new approach to treating lung cancer by combining immunotherapy and radiation. Atezolizumab is an immunotherapy drug that helps the immune system recognize and attack cancer cells, unlike traditional chemotherapy that directly targets and kills cancer cells. When paired with Stereotactic Body Radiation Therapy (SBRT), which precisely targets tumors with high doses of radiation, the combination could enhance the overall effectiveness and reduce damage to healthy tissue. This dual approach aims to improve patient outcomes and may offer a more targeted and potentially less toxic alternative to existing treatments like chemotherapy and conventional radiotherapy.

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

Research shows that combining atezolizumab with stereotactic body radiation therapy (SBRT) may help treat early-stage non-small cell lung cancer (NSCLC). In this trial, one group of participants will receive both atezolizumab, which boosts the immune system to fight cancer, and SBRT. Studies have found that combining atezolizumab with SBRT is safe and may be more effective than radiation alone. Another group of participants will receive only SBRT. This combination has been tested in patients who cannot undergo surgery, and results suggest it could be better than using only radiation. Overall, this treatment approach is feasible and may improve outcomes for patients with early-stage lung cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Megan E Daly

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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

My liver tests are within the normal range.

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

You need to have a lung function test done within the last 90 days before joining the study.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02599454

NCT02599454 | Atezolizumab and Stereotactic Body ... This phase I trial studies the side effects and best dose of atezolizumab that can be given together with stereotactic body radiation therapy (SBRT) in ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37658083/

Atezolizumab plus stereotactic ablative radiotherapy for ... Stereotactic ablative radiotherapy (SABR) is a standard-of-care for medically-inoperable-early-stage non-small cell lung cancer (NSCLC).

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.9011

Atezolizumab plus stereotactic ablative therapy for ... Atezolizumab plus SABR is feasible, safe and shows an efficacy signal in medically inoperable early stage NSCLC.

4. nature.com nature.com/articles/s41467-023-40813-w

Atezolizumab plus stereotactic ablative radiotherapy for ... Stereotactic ablative radiotherapy (SABR) is a standard-of-care for medically-inoperable-early-stage non-small cell lung cancer (NSCLC).

5. febs.onlinelibrary.wiley.com febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13330

Atezolizumab and stereotactic body radiotherapy in patients ... In this clinical trial, we investigated the tolerability, efficacy and circulating tumour DNA responses in patients with metastatic lung cancer ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301625004468

Atezolizumab and Stereotactic Body Radiation in ... The most common grade ≥2 toxicities at least possibly attributed to study therapy included lymphopenia (n = 6; 29%), nausea/vomiting (n = 3; 14 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9980306/

safety, clinical activity and ctDNA responses—the ComIT‐1 ... We found the combined treatment to be safe with grade 3 toxicity reported in three patients. As the best overall response, four patients had a partial response.