Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody for Breast Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Chemotherapy, Immunotherapy, Vaccinations

Disqualifiers: Uncontrolled illness, Active infection, HIV, others

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

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CF33-hNIS-antiPDL1 for individuals with triple-negative breast cancer that has metastasized. The trial aims to assess its safety, potential side effects, and optimal dosage. CF33-hNIS-antiPDL1 is a specially designed virus that targets and breaks down cancer cells. Individuals who have tried at least two other treatments for advanced breast cancer without success and have a type of tumor suitable for injection might be eligible for this trial. 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 innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop chemotherapy, biological therapy, immunotherapy, or investigational therapy at least 14 days before starting the study treatment. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that CF33-hNIS-antiPDL1 is likely to be safe for humans?

Research has shown that CF33-hNIS-antiPDL1, a virus used to fight cancer, is being tested for safety in treating advanced triple-negative breast cancer. In earlier animal studies, various doses of this virus were well tolerated, meaning they did not cause serious side effects. The treatment also helped shrink tumors and improved the body's immune response to cancer.

These early results are encouraging, but it is important to remember they come from animal studies. This current study marks the first time the treatment is being tested in humans. Researchers are still gathering crucial safety information. However, reaching this stage of the study suggests some confidence in its safety so far. Participants in the trial will help researchers learn more about how well people tolerate this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CF33-hNIS-antiPDL1 for breast cancer because it represents a novel approach using an oncolytic virus. Unlike traditional treatments like chemotherapy, which targets rapidly dividing cells indiscriminately, this therapy uses a genetically engineered virus to selectively infect and kill cancer cells. It also includes an anti-PD-L1 antibody, which can help the immune system recognize and attack the cancer more effectively. This dual action—directly attacking tumor cells and boosting the immune response—has the potential to be more effective and less toxic than current treatments.

What evidence suggests that CF33-hNIS-antiPDL1 might be an effective treatment for metastatic triple negative breast cancer?

Research has shown that CF33-hNIS-antiPDL1, the treatment under study in this trial, may help treat triple negative breast cancer (TNBC). In studies with mice, this virus boosted the immune system's response to tumors, shrank the tumors, and extended the mice's lifespan. Another study found that it greatly reduced a cancer marker called CA 15-3, and the patient remained disease-free. This virus targets and breaks down cancer cells, aiding the body in fighting cancer more effectively. These findings suggest that CF33-hNIS-antiPDL1 could be a promising treatment for TNBC. ^{1 2 3 4 5}

Who Is on the Research Team?

Jamie Rand

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic triple negative breast cancer who have tried at least two treatments without success. Participants must not be pregnant, breastfeeding, or have other cancers; they should also agree to use birth control and provide biopsies. They need normal blood counts, liver function within certain limits, and cannot join if they've had recent vaccines or infections.

Inclusion Criteria

I have recovered from major side effects of my previous cancer treatment.

My breast cancer is triple negative and has spread to other parts.

Documented informed consent of the participant and/or legally authorized representative

Exclusion Criteria

I am currently taking antibiotics for an infection.

Inability to comply with study procedures

I do not have any uncontrolled serious illnesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive CF33-hNIS-antiPDL1 intratumorally on days 1 and 15, repeating every 28 days for up to 3 cycles

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

1 year

1 visit at 30 days, then every 3 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• CF33-hNIS-antiPDL1

Trial Overview The trial tests CF33-hNIS-antiPDL1, an oncolytic virus designed to infect and break down tumor cells in patients with advanced breast cancer. It's a phase I study focusing on the safety of this treatment and finding the right dosage.

How Is the Trial Designed?

Group I: Treatment (CF33-hNIS-antiPDL1) Experimental Treatment 1 Intervention

Patients receive CF33-hNIS-antiPDL1 IT on days 1 and 15. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Imugene Limited

Industry Sponsor

Trials

7

Recruited

340+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

Anti-PD-1 and anti-PD-L1 antibodies show modest response rates as standalone treatments for metastatic breast cancer, but they are generally well tolerated and can provide significant, lasting benefits for some patients.

These antibodies can be safely combined with various systemic therapies, including chemotherapy and targeted therapies, as well as radiotherapy, suggesting potential for enhanced effectiveness in treating metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two may be better than one: PD-1/PD-L1 blockade combination approaches in metastatic breast cancer. Page, DB., Bear, H., Prabhakaran, S., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10640805/

CF33-hNIS-anti-PD-L1 oncolytic virus followed by ... A significant reduction in cancer antigen 15-3 (CA 15-3) was documented over the course of treatment (Figure 2). Patient remained disease-free ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05081492

NCT05081492 | CF33-hNIS-antiPDL1 for the Treatment of ... This phase I trial tests the safety, side effects, and best dose of CF33-hNIS-antiPDL1 in treating patients with triple negative breast cancer that has spread ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S075333222500602X

CF33-hNIS-antiPDL1 enhances immunogenicity and anti ... Intraperitoneal CF33-hNIS-antiPDL1 increased antitumor immunity, reduced tumor burden, and prolonged survival in these mice. •. The results provide a ...

4. cell.com cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(21)00188-1

A comprehensive preclinical study supporting clinical trial ... The results of these preclinical studies support the use of CF33-hNIS-anti-PD-L1 in a first-in-human trial in patients with TNBC. Graphical ...

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1565244/full

hNIS-based imaging to monitor treatment with the novel ... CF33-hNIS-antiPDL1, an oncolytic orthopoxvirus, shows robust anti-cancer activity in TNBC xenografts in mice. CF33-hNIS-antiPDL1-infected tumor cells express ...