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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of combining two treatments, BO-112 (an experimental treatment) and nivolumab (also known as Opdivo, an immunotherapy drug), before surgery for individuals with soft tissue sarcoma. The goal is to determine if this combination can enhance the immune system's ability to fight the cancer and prevent its growth and spread. The trial seeks participants with a type of soft tissue sarcoma that is operable and has tumors suitable for injection. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

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.

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

Research has shown that the combination of BO-112 and nivolumab is generally well-tolerated, though some risks exist. In earlier studies, BO-112 was linked to a few cases of reversible thrombocytopenia, a temporary drop in blood platelets. These more serious side effects were rare and occurred in only a small number of patients.

Nivolumab is more familiar because it is already used for other types of cancer. It is generally safe, but some patients might experience side effects like tiredness, rash, or itchy skin. These side effects are usually mild and manageable.

Together, these treatments have shown promising results with manageable side effects. It is important to carefully consider the potential benefits and risks. Always consult healthcare providers to understand what this means personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Nivolumab and BO-112 for soft tissue sarcoma because it offers a unique approach to treatment. Unlike the standard chemotherapy options, this combo leverages the immune system in a novel way. Nivolumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. BO-112, on the other hand, is a nanoplexed form of Poly I:C, delivered directly into the tumor to enhance the immune response. Together, they could potentially boost the effectiveness of the body's natural defenses against cancer, providing a promising alternative to traditional therapies.

What evidence suggests that this treatment might be an effective treatment for soft tissue sarcoma?

Research has shown that BO-112, when injected directly into tumors, can activate the immune system both locally and throughout the body. This activation may help the immune system fight cancer cells more effectively. In studies involving 100 cancer patients, BO-112 proved to be safe and effective when used in this manner.

Nivolumab is another treatment that has successfully treated certain types of sarcoma, a kind of cancer. It works by blocking a protein that usually prevents the immune system from attacking cancer cells. Some studies have shown that combining nivolumab with other treatments resulted in a 25% response rate in certain sarcomas. In this trial, participants will receive both BO-112 and nivolumab, which together might enhance the body's ability to target and destroy sarcoma cells before surgery. ^{1 2 6 7 8}

Who Is on the Research Team?

Vishruth Reddy, MD, PhD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

Citations

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A surgically optimized intraoperative poly(I:C)-releasing ... Together, these data show that the optimized intraoperative poly(I:C)-releasing hydrogel prevents tumor recurrence following surgery in multiple ...

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A surgically optimized intraoperative poly(I:C)-releasing ... Together, these data show that the optimized intraoperative poly(I:C)-releasing hydrogel prevents tumor recurrence following surgery in multiple ...

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the potential of intratumoral immunotherapy for locally ... For non-small cell lung cancer, results from clinical trials have shown favorable pathologic response rates with minimal adverse events when ...