Nivolumab +/- Azacitidine for Osteosarcoma

Recruiting at 24 trial locations

Overseen By Jessica R Crimella, BSN, RN

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Pregnancy, Autoimmune disorders, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

21 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and efficacy of nivolumab, or nivolumab in combination with azacitidine in participants with recurrent, resectable osteosarcoma

Will I have to stop taking my current medications?

The trial requires that you stop taking corticosteroids or other immunosuppressive medications. If you are on these medications, you would need to discontinue them to participate in the study.

What data supports the effectiveness of the drug Nivolumab for treating osteosarcoma?

Research shows that Nivolumab, a drug that helps the immune system fight cancer, has been effective in treating other cancers like lung cancer and has shown promise in stabilizing tumors in osteosarcoma patients when combined with other treatments. ^{1 2 3 4 5}

How is the drug Nivolumab +/- Azacitidine unique for treating osteosarcoma?

Nivolumab +/- Azacitidine is unique for treating osteosarcoma because it involves the use of immunotherapy, specifically targeting the PD-1 pathway, which is not a standard approach for this cancer type. This treatment leverages the body's immune system to fight cancer cells, offering a novel option for patients with limited treatment choices. ^{3 4 6 7 8}

Research Team

Patrick Thompson, M.D.

Principal Investigator

University of North Carolina, Chapel Hill

Mihaela Druta, MD

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute, Coordinating Center

Eligibility Criteria

This trial is for people with osteosarcoma that has come back and can be surgically removed. They should have recovered from previous treatments, not have metastasis beyond the lungs, and must agree to surgery for all tumors. Participants need normal organ function, no severe autoimmune disorders or uncontrolled illnesses, no history of certain allergies or reactions to similar drugs, and cannot be on immunosuppressants or other cancer treatments.

Inclusion Criteria

My organs and bone marrow are functioning normally.

You cannot participate in the clinical trial if you have had an organ transplant in the past.

My osteosarcoma has come back in my lungs only.

Exclusion Criteria

Intercurrent Illnesses: Patients with uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection, Symptomatic congestive heart failure, Unstable angina pectoris, Cardiac arrhythmia, Psychiatric illness/social situations that would limit compliance with study requirements, Autoimmune disorders: Patients with a history of any Grade autoimmune disorder are not eligible. Asymptomatic laboratory abnormalities (e.g., ANA, rheumatoid factor, altered thyroid function studies) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder. Patients with ≥ Grade 2 hypothyroidism due to history of autoimmunity are not eligible. Note: Hypothyroidism due to previous irradiation or thyroidectomy will not impact eligibility, Allergies: Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Nivolumab (e.g., another humanized antibody) or Azacitidine are not eligible, Safety and Monitoring: Patients who are considered unable to comply with the safety monitoring requirements of the study are not eligible, Patients with known HIV or hepatitis B or C are excluded, Patients who have received prior solid organ transplantation are not eligible, Patients who have received prior anti-PD-1 directed therapy (mAb or small molecule) are not eligible

I am not taking steroids, immunosuppressants, or any cancer treatments.

I am using two forms of birth control, one highly effective and another as required.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive 1 cycle of neoadjuvant Nivolumab or Nivolumab + Azacitidine

4 weeks

Surgery

Surgery to render participants in surgical remission

Adjuvant Treatment

Participants continue to receive Nivolumab or Nivolumab + Azacitidine for up to 12 additional cycles or until recurrence

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Azacitidine
• Nivolumab
• Post Treatment Surgery

Trial Overview The study tests the safety and effectiveness of Nivolumab alone or combined with Azacitidine in patients whose osteosarcoma has returned but can still be operated on. The goal is to see how well these treatments work before they go through surgery to remove their tumors.

Participant Groups

Group I: Dose Escalation, Resection, Dose Expansion Experimental Treatment 3 Interventions

Participants will receive 1 cycle of neoadjuvant Nivolumab or Nivolumab + Azacitidine, followed by surgery to render them in surgical remission. Subsequently they will continue to receive Nivolumab or Nivolumab + Azacitidine for 12 additional cycles or until recurrence, whichever occurs first. Once the recommended Phase II dose (RP2D) is identified during Phase I, the Dose Expansion Phase II will be opened at this dose level. The Phase II portion of the study will consist of a maximum 33 evaluable patients (27-30 in addition to the 3-6 enrolled at RP2D on the Phase I portion).

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

The anti-PD-L1 antibody ZKAB001 demonstrated a manageable safety profile in a Phase I/II study involving 21 patients with localized high-grade osteosarcoma, with the most common side effects being thyroiditis (76.2%) and dermatitis (42.9%).

Preliminary efficacy results indicated a promising 24-month event-free survival rate of 71.4% and a 100% overall survival rate, particularly benefiting patients with PD-L1 positive or MSI-H subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Maintenance Therapy for Localized High-Grade Osteosarcoma: An Open-Label Phase I/II Trial of the Anti-PD-L1 Antibody ZKAB001. Zhou, Y., Yang, Q., Dong, Y., et al.[2023]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Rizvi, NA., Mazières, J., Planchard, D., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

References

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

First-in-Maintenance Therapy for Localized High-Grade Osteosarcoma: An Open-Label Phase I/II Trial of the Anti-PD-L1 Antibody ZKAB001. [2023]

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

Profiling targetable immune checkpoints in osteosarcoma. [2021]

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

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]

4. England pubmed.ncbi.nlm.nih.gov

NGS-analysis to the rescue: dual checkpoint inhibition in metastatic osteosarcoma - a case report and review of the literature. [2022]

5. Australia pubmed.ncbi.nlm.nih.gov

Prognostic Value of Programmed Cell Death 1 Ligand-1 (PD-L1) or PD-1 Expression in Patients with Osteosarcoma: A Meta-Analysis. [2022]

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

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. [2022]

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

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. [2018]