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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerance of combining Atezolizumab (Tecentriq) with radiation therapy and surgery for treating osteosarcoma that has returned in the lungs. The goal is to determine if this combination can effectively treat the cancer without causing severe side effects. Suitable participants have osteosarcoma that has recurred in the lungs and can be surgically removed, with no cancer spread outside the lungs. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking cancer research.

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.

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

Research has shown that atezolizumab, a type of immunotherapy, is generally safe for adults. Common side effects include fever, tiredness, and constipation. However, its safety for children or pregnant women remains unknown.

Studies have found that stereotactic body radiation therapy (SBRT) is usually safe for treating osteosarcoma, a type of bone cancer. Most side effects are mild, such as skin irritation or temporary pain. Only a few individuals experience more serious issues, like difficulty swallowing or lung inflammation, and these are rare.

Overall, both atezolizumab and SBRT appear well-tolerated by patients. However, as with any treatment, there is always a chance of side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for osteosarcoma, which typically involves surgery and chemotherapy, atezolizumab offers a novel approach by harnessing the body's immune system. Atezolizumab is an immune checkpoint inhibitor that targets the PD-L1 protein, helping the immune system recognize and attack cancer cells more effectively. Researchers are excited because combining atezolizumab with radiation and surgery could potentially enhance the overall treatment effectiveness, offering a new pathway for tackling this aggressive cancer. This combination approach aims to not only target the primary tumor but also to address potential metastatic sites, potentially improving outcomes for patients.

What evidence suggests that this trial's treatments could be effective for osteosarcoma?

In this trial, participants will receive a combination of atezolizumab, stereotactic body radiation therapy (SBRT), and surgery. Research has shown that atezolizumab can shrink tumors in nearly 40% of people with alveolar soft part sarcoma, a rare type of cancer. It has also shown promise in advanced cases, with lasting effects in about one-third of patients. Studies have found that SBRT is safe and effective for treating recurring and spreading osteosarcoma, with success rates of about 85% to 88% over a year. Combining these treatments with surgery might offer a comprehensive approach to managing cancer that returns in the lungs for osteosarcoma patients. ^{1 4 6 7 8}

Who Is on the Research Team?

Thomas Cash, MD, MSc

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

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 bone marrow is functioning well.

My liver is working 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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 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 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]

Citations

1. cancer.gov cancer.gov/news-events/cancer-currents-blog/2023/atezolizumab-effective-alveolar-soft-part-sarcoma

Atezolizumab Shrinks Alveolar Soft Part Sarcomas - NCI Treatment with atezolizumab (Tecentriq) shrank tumors in nearly 40% of people with alveolar soft part sarcoma, according to new clinical ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303383

Atezolizumab for Advanced Alveolar Soft Part Sarcoma Atezolizumab was effective at inducing sustained responses in approximately one third of patients with advanced ASPS.

3. onclive.com onclive.com/view/dr-liu-on-the-5-year-os-data-with-atezolizumab-and-chemotherapy-in-es-sclc

Dr Liu on the 5-Year OS Data With Atezolizumab and ... Furthermore, landmark OS rates were 16% (95%, 11%-21%) and 13% (95% CI, 8%-18%) at years 3 and 4, respectively. These outcomes emphasize the ...

4. cancernetwork.com cancernetwork.com/view/atezolizumab-combo-real-world-data-match-clinical-trial-efficacy-in-sclc

Atezolizumab Combo Real-World Data Match Clinical Trial ... In the overall efficacy population, the median overall survival (OS) was 16.5 months (95% CI, 14.9-18.2), and the 12-month OS rate was 63.7% (95 ...

5. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT263/742278/Abstract-CT263-Atezolizumab-clinical-trial

Abstract CT263: Atezolizumab clinical trial biopsies reveal ... Abstract CT263: Atezolizumab clinical trial biopsies reveal varied immune landscapes in clear cell sarcoma and chondrosarcoma Available.

6. fda.gov fda.gov/media/143360/download

Clinical Review of Efficacy Supplement (atezolizumab) The safety and antitumor activity of TECENTRIQ were assessed but not established in a single-arm, multi-center, multi-cohort trial (NCT02541604) ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK567758/

Atezolizumab - StatPearls - NCBI Bookshelf - NIH Toxicity. There is no available data regarding the safety of atezolizumab in pediatric patients and pregnant or breastfeeding women.[12][11] ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.10524

A phase I/II study of atezolizumab in pediatric and young ... Common AEs were pyrexia (37%), fatigue (34%) and constipation (32%). 2/5 patients with HL had a partial response (PR); the only patient with ...