Atezolizumab + Radiation + Surgery for Osteosarcoma

(AflacST2301 Trial)

Overseen By Chloe Edgerton

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must not be taking: Immunosuppressants, others

Disqualifiers: Pregnancy, Extrapulmonary metastases, Autoimmune disorders, 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: Unknown

Duration: 2 cycles of Atezolizumab, followed by surgery and resumption of Atezolizumab 14-28 days post-op

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to determine the safety and tolerability of combined Atezolizumab, stereotactic body radiation therapy (SBRT), and surgical resection of pulmonary metastases in patients with pulmonary recurrence of osteosarcoma

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there are specific time requirements for stopping certain treatments like chemotherapy, growth factors, and other therapies before joining. It's best to discuss your current medications with the trial team to get a clear answer.

What data supports the effectiveness of the drug Atezolizumab in combination with radiation and surgery for osteosarcoma?

Atezolizumab, when used for bladder cancer, has shown significant tumor responses and improved survival rates, suggesting its potential effectiveness in other cancers. Additionally, combining Atezolizumab with radiation therapy has shown promising early responses in lung cancer, indicating that this combination might enhance treatment outcomes in osteosarcoma as well. ^{1 2 3 4 5}

Is the combination of Atezolizumab, Radiation, and Surgery generally safe for humans?

Atezolizumab, also known as Tecentriq, has been shown to have a favorable safety profile in various studies for different types of cancer, including bladder cancer and non-small cell lung cancer. It is generally considered safe, with ongoing trials to further assess its safety in combination with other treatments like radiation. ^{1 3 5 6 7}

How does the drug atezolizumab differ from other treatments for osteosarcoma?

Atezolizumab is unique because it is a monoclonal antibody that targets PD-L1, a protein that helps cancer cells evade the immune system, thereby boosting the body's immune response against tumors. This approach is different from traditional chemotherapy or surgery, as it specifically enhances the immune system's ability to fight cancer cells. ^{1 3 4 5 8}

Research Team

Thomas Cash, MD, MSc

Principal Investigator

Emory University

Eligibility Criteria

This trial is for patients with osteosarcoma that has come back and spread to the lungs. Participants must be healthy enough for surgery, radiation therapy, and immunotherapy. Specific details about who can join are not provided here.

Inclusion Criteria

Any side effects from my previous treatments are mild or stable.

My liver is working well.

My bone marrow is functioning well.

Exclusion Criteria

I have had a stem cell or organ transplant in the past.

I have a history of HIV, hepatitis B, or hepatitis C.

I have had pneumonitis before or have it now.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Atezolizumab followed by SBRT and surgical resection of pulmonary metastases

2 cycles of Atezolizumab, followed by surgery and resumption of Atezolizumab 14-28 days post-op

Follow-up

Participants are monitored for safety, tolerability, and disease progression

12 months

Treatment Details

Interventions

• Atezolizumab
• Stereotactic Body Radiation Therapy (SBRT)
• Surgical Resection

Trial Overview The study is testing the safety of combining Atezolizumab (an immunotherapy drug), SBRT (a precise form of radiation therapy), and surgery in patients whose osteosarcoma has returned and spread to their lungs.

Participant Groups

Group I: Dose escalation Experimental Treatment 3 Interventions

Unilateral: Participants start with atezolizumab, followed ≤ 1 week later by SBRT at the assigned dose for a single lesion. After 2 cycles, those with unilateral disease undergo complete surgical resection, including all lung nodules, including the radiated one, as per osteosarcoma standard care. Atezolizumab resumes 14-28 days post-op, per protocol criteria, barring toxicity or disease progression. Bilateral: Subjects first undergo surgery on the non-SBRT side. 7-14 days later, they start atezolizumab, followed ≤ 1 week later by SBRT on the other lesion. After 2 cycles of atezolizumab, surgery on the contralateral side removes all lung nodules, including the radiated one, per standard care. Atezolizumab resumes 14-18 days post-op, per protocol criteria, barring toxicity or disease progression

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?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

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

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

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 phase 2 study involving 45 patients with invasive bladder cancer, the combination of radiation therapy and atezolizumab resulted in a high pathologic complete response (pCR) rate of 84.4%, particularly in older patients and those with high PD-L1 expression.

The treatment was associated with acceptable toxicity, with 93.3% of patients experiencing adverse events, mostly mild to moderate, and only 13.3% experiencing grade 3 adverse events, indicating that this approach could be a viable bladder-preserving option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. Kimura, T., Ishikawa, H., Nagumo, Y., et al.[2023]

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 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]

In a real-world study of 1002 patients with previously treated non-small cell lung cancer (NSCLC), atezolizumab showed an 18-month overall survival rate of 41.1%, confirming its effectiveness outside of clinical trial settings.

The safety profile was acceptable, with an overall adverse event rate of 43.9% and immune-related adverse events at 19.0%, but caution is advised for patients with poorer performance status (ECOG ≥ 2), as they had a significantly lower survival rate of 14.3%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Atezolizumab Monotherapy in Previously Treated Japanese Patients With Unresectable Advanced or Recurrent NSCLC: A Multicenter, Prospective, Observational Study (J-TAIL). Miura, S., Nishio, M., Akamatsu, H., et al.[2023]

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 therapy, showed a significant survival benefit in patients with advanced non-small-cell lung cancer, with 28% of patients treated with atezolizumab surviving long-term (≥24 months) compared to 18% in the docetaxel group after a minimum follow-up of 26 months.

The treatment was well tolerated, even with a median treatment duration of 18 months, and long-term survivors included both responders and patients with progressive disease, indicating that atezolizumab can benefit a broader range of patients regardless of initial response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival in patients with advanced non-small-cell lung cancer treated with atezolizumab versus docetaxel: Results from the randomised phase III OAK study. von Pawel, J., Bordoni, R., Satouchi, M., et al.[2022]

References

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

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

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. [2023]

4. 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]

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

Atezolizumab: First Global Approval. [2019]

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

Effectiveness and Safety of Atezolizumab Monotherapy in Previously Treated Japanese Patients With Unresectable Advanced or Recurrent NSCLC: A Multicenter, Prospective, Observational Study (J-TAIL). [2023]

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

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

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

Long-term survival in patients with advanced non-small-cell lung cancer treated with atezolizumab versus docetaxel: Results from the randomised phase III OAK study. [2022]