Pre-Surgery Nivolumab + BO-112 for Soft Tissue Sarcoma

Overseen By Carol Felix

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Live vaccines, Immunosuppressants

Disqualifiers: Pregnancy, Autoimmune disease, Immunosuppression, others

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

Compensation: Varies

Number of Visits: 2

Duration: 7 weeks

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects of BO-112 when given together with nivolumab before surgery in treating patients with soft tissue sarcoma that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with BO-112, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab and BO-112 before surgery may work better in treating patients with soft tissue sarcoma compared to nivolumab alone.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any concurrent chemotherapy, immunotherapy, or biologic therapy for cancer treatment, and you must not have received any live vaccine within 30 days prior to registration.

What data supports the effectiveness of the drug Nivolumab + BO-112 for soft tissue sarcoma?

Research shows that drugs like Nivolumab, which are immune checkpoint inhibitors, have helped some patients with soft tissue sarcoma achieve long-term remission, even when other treatments failed. Although data is limited, combining these drugs with other therapies has shown promise in making tumors more responsive to treatment. ^{1 2 3 4 5}

Is the combination of Nivolumab and BO-112 safe for humans?

Nivolumab, when used in combination with another drug called ipilimumab, has been shown to be generally well tolerated in patients with advanced soft tissue sarcoma, with common side effects including fatigue and cough. Serious side effects were rare, with a small percentage of patients experiencing severe conditions like high blood sugar and heart inflammation. ^{1 3 4 6 7}

How is the drug Nivolumab + BO-112 different from other treatments for soft tissue sarcoma?

The combination of Nivolumab and BO-112 is unique because it combines an immune checkpoint inhibitor (Nivolumab) with a novel agent (BO-112) that enhances the immune response, potentially offering a new approach for treating soft tissue sarcoma, which has limited effective treatment options. ^{1 3 5 6 8}

Research Team

Vishruth Reddy, MD, PhD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with certain types of soft tissue sarcoma that can be surgically removed. Participants must have a specific level of blood cells, not be breastfeeding, agree to use effective contraception methods if applicable, and provide consent. They should not have received live vaccines recently or have any condition that could affect their participation.

Inclusion Criteria

WOCBP must have a negative pregnancy test within 24 hours prior to the start of study drug

Hemoglobin >= 9 g/dL

Absolute neutrophil count >= 1,000/mm^3

Exclusion Criteria

I have or had fibromyalgia, myositis, myocarditis, or myasthenia gravis.

Prisoners or subjects who are involuntarily incarcerated

I am not currently on any chemotherapy, immunotherapy, or biologic therapy for cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BO-112 intratumorally on days 8 and 15 or 1, 8, and 15, and nivolumab intravenously on day 8. Standard of care radiation therapy is administered on days 8-12, followed by surgical resection on day 26 to 50.

7 weeks

Multiple visits for drug administration and surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Follow-up visits at 2 weeks, 3 months, and between 6-12, 12-18, and 18-24 months

Treatment Details

Interventions

• Definitive Surgical Resection
• Nanoplexed Poly I:C BO-112
• Nivolumab

Trial Overview The trial is testing the combination of BO-112 and nivolumab given before surgery compared to nivolumab alone. These are immunotherapies designed to help the immune system fight cancer by stopping tumor growth and spread. The goal is to see if this combo works better in treating soft tissue sarcoma.

Participant Groups

Group I: Treatment (BO-112, nivolumab) Experimental Treatment 4 Interventions

Patients receive BO-112 intratumorally on days 8 and 15 or 1, 8, and 15 and nivolumab IV over 30-60 minutes on day 8 in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy on days 8-12 for a total of 5 fractions. Patients then undergo standard of care definitive surgical resection on day 26 to 50.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Highlight Therapeutics

Industry Sponsor

Trials

7

Recruited

210+

Findings from Research

Checkpoint inhibitor therapy, specifically ipilimumab and nivolumab, can lead to long-term remission in patients with advanced soft tissue sarcoma, even in cases with zero percent PD-L1 expression, suggesting efficacy regardless of this biomarker.

The combination of checkpoint inhibitors with treatments like cryoablation may enhance the effectiveness of immunotherapy, indicating a potential strategy for improving outcomes in soft tissue sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Remission with Ipilimumab/Nivolumab in Two Patients with Different Soft Tissue Sarcoma Subtypes and No PD-L1 Expression. Zhou, M., Bui, N., Lohman, M., et al.[2021]

In a study of treatment-naive patients with PD-L1 positive metastatic soft tissue sarcomas, the combination of nivolumab and ipilimumab (NPI) significantly improved overall survival (12.2 months) and progression-free survival (4.1 months) compared to nivolumab alone (NIV), which had overall survival of 9.2 months and progression-free survival of 2.2 months.

While NPI showed greater efficacy in extending survival, it was associated with a higher incidence of severe adverse events (72.9% in NPI vs. 27.1% in NIV), indicating that while it may be more effective, it is also less tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab versus nivolumab in individuals with treatment-naive programmed death-ligand 1 positive metastatic soft tissue sarcomas: a multicentre retrospective study. Chen, Y., Liu, X., Liu, J., et al.[2023]

In a phase 2 trial involving 62 patients with advanced or metastatic sarcoma, the combination of durvalumab and tremelimumab showed a promising progression-free survival rate of 49% at 12 weeks, indicating its potential efficacy as a treatment option.

While the treatment was generally active, it was associated with some serious adverse events, including one case of grade 5 pneumonitis and colitis, highlighting the need for careful monitoring of patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. Somaiah, N., Conley, AP., Parra, ER., et al.[2023]

In a study of patients with advanced soft tissue sarcoma treated with the combination of ipilimumab and nivolumab, the objective response rate was 15%, with one complete response and five partial responses, indicating some level of efficacy.

The treatment was generally well tolerated, with a clinical benefit rate of 34% and a median overall survival of 12 months, although 58% of patients experienced adverse events, primarily mild, with a small percentage facing more severe complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab for soft tissue sarcoma: a single institution retrospective review. Zhou, M., Bui, N., Bolleddu, S., et al.[2021]

In a phase II study of pembrolizumab for advanced sarcoma, a 17.5% response rate was observed, particularly in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma, indicating its potential efficacy in these subtypes.

Higher densities of activated T cells and tumor-associated macrophages expressing PD-L1 in pre-treatment biopsies were associated with better responses to pembrolizumab, suggesting that specific immune features may predict treatment outcomes and progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab. Keung, EZ., Burgess, M., Salazar, R., et al.[2021]

References

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

Long-Term Remission with Ipilimumab/Nivolumab in Two Patients with Different Soft Tissue Sarcoma Subtypes and No PD-L1 Expression. [2021]

2. China pubmed.ncbi.nlm.nih.gov

Turning 'Cold' tumors 'Hot': immunotherapies in sarcoma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab versus nivolumab in individuals with treatment-naive programmed death-ligand 1 positive metastatic soft tissue sarcomas: a multicentre retrospective study. [2023]

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

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. [2023]

5. England pubmed.ncbi.nlm.nih.gov

PD1/PD-L1 targeting in advanced soft-tissue sarcomas: a pooled analysis of phase II trials. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab for soft tissue sarcoma: a single institution retrospective review. [2021]

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

Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab. [2021]

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

Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells. [2023]