Measles Virus-Based Vaccine for Breast Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Corticosteroids, others

Disqualifiers: Active infection, Heart disease, CNS metastases, HIV, others

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

Compensation: Varies

Number of Visits: 4

Duration: 3-9 weeks

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new breast cancer treatment using a modified measles virus called MV-s-NAP (Oncolytic Measles Virus Encoding Helicobacter pylori Neutrophil-activating Protein). The goal is to determine if this virus can safely target and kill cancer cells in patients whose breast cancer has spread. Researchers examine the virus's effects on cancer by collecting various samples and conducting imaging tests. This trial is suitable for those with advanced breast cancer that has not responded to other treatments and who have measurable cancer that can be safely accessed for treatment. 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 does not specify if you must stop taking your current medications, but it does mention that certain therapies and medications, like chemotherapy, immunotherapy, and HER2 directed therapy, must not have been taken recently. It's best to discuss your specific medications with the trial team to see if they might interfere with the study.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the modified measles virus, MV-s-NAP, used in this trial, has been safe in early studies. These studies found that MV-s-NAP is generally well-tolerated, with most participants not experiencing serious side effects. Previous trials have demonstrated that similar measles viruses are safe for people.

In preclinical tests conducted in the lab or on animals, MV-s-NAP did not cause major harmful effects. This provides some reassurance about its safety for potential trial participants. However, it's important to remember that this is an early-stage trial. While earlier results are promising, the treatment is still under close observation for any possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for breast cancer, like chemotherapy, target rapidly dividing cells but can affect healthy cells too. This new approach using an oncolytic measles virus encoding the Helicobacter pylori neutrophil-activating protein (MV-s-NAP) is different because it specifically targets and destroys cancer cells while sparing normal cells. Researchers are excited because this virus-based therapy not only directly attacks tumors but also stimulates the immune system to recognize and fight cancer cells, potentially leading to fewer side effects and a more targeted treatment. This innovative mechanism could offer a promising alternative to traditional therapies, which often come with significant side effects.

What evidence suggests that this treatment might be an effective treatment for metastatic breast cancer?

Research has shown that a modified measles virus, called MV-s-NAP, holds promise in fighting breast cancer. In lab and animal studies, MV-s-NAP grew inside and destroyed breast cancer cells. This virus contains a special protein, neutrophil-activating protein (NAP), which boosts the immune system. This protein might help the body fight cancer more effectively. Although human studies provide limited information, these early results suggest that MV-s-NAP could target and kill cancer cells. Participants in this trial will receive MV-s-NAP in different dosing schedules across separate treatment arms to evaluate its effectiveness and safety. ^{1 5 6 7 8}

Who Is on the Research Team?

Siddhartha Yadav, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

Adults with invasive breast cancer that has spread (metastatic) and no curative standard therapy available. Must have good organ function, acceptable blood counts, ECOG status 0-2, and a life expectancy of at least 12 weeks. Cannot be pregnant or have had certain treatments recently.

Inclusion Criteria

I am taking medication for bone complications due to cancer and have tolerated it well.

I am able to care for myself and perform daily activities.

Willingness to return to the Mayo Clinic enrolling institution for follow-up

Exclusion Criteria

I need regular blood transfusions.

I have not had HER2 therapy in the last 3 weeks.

My cancer is causing or might soon cause serious problems by pressing on or invading into nearby organs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive MV-s-NAP intratumorally on day 1. Cohort 1 receives a single treatment, while Cohort 2 receives treatment every 21 days for up to 3 cycles.

3-9 weeks

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months during year 1 and every 6 months during year 2.

Up to 2 years

Every 3 months in year 1, every 6 months in year 2 (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Oncolytic Measles Virus Encoding Helicobacter pylori Neutrophil-activating Protein

Trial Overview The trial is testing MV-s-NAP, a modified measles virus designed to target and destroy breast cancer cells by producing an inflammatory protein called NAP. The study will determine the best dose and monitor its effects on metastatic breast cancer through various tests.

How Is the Trial Designed?

Group I: Cohort 3 (Every 14 day MV-s-NAP) Experimental Treatment 5 Interventions

Patients receive MV-s-NAP IT on day 1 of each cycle. Cycles repeat every 14 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, tumor biopsy and blood and urine sample collection throughout the study.

Group II: Cohort 2 (Every 21 day MV-s-NAP) Experimental Treatment 4 Interventions

Patients receive MV-s-NAP IT on day 1 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, tumor biopsy, and blood and urine sample collection throughout the study. (CLOSED TO ACCRUAL 6/9/2025)

Group III: Cohort 1 (single treatment MV-s-NAP) Experimental Treatment 5 Interventions

Patients receive MV-s-NAP IT on day 1 in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, tumor biopsy, and blood and urine sample collection throughout the study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Engineered measles virus strains expressing Helicobacter pylori neutrophil-activating protein (NAP) effectively target and destroy metastatic breast cancer cells, leading to a significant increase in median survival (65 days vs. 29 days) in a pleural effusion xenograft model.

The therapeutic effect of these viruses is linked to a strong Th1 immune response, with increased levels of pro-inflammatory cytokines like TNF-α and IL-6, suggesting that combining oncolytic viruses with immunomodulators like NAP could enhance cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of immunomodulatory neutrophil-activating protein of Helicobacter pylori enhances the antitumor activity of oncolytic measles virus. Iankov, ID., Allen, C., Federspiel, MJ., et al.[2021]

Measles virus (MV) vaccine strains show strong potential as cancer treatments due to their ability to selectively target and kill tumor cells while sparing healthy cells.

These MV strains not only demonstrate significant preclinical effectiveness against various tumor models but also retain their oncolytic properties even when modified for specific targeting, making them a versatile option for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of oncolytic measles virus: promises and challenges. Galanis, E.[2010]

Retargeted measles virus (MV) strains derived from the Edmonston vaccine lineage show promising potential as an oncolytic therapy for treating metastatic cancers, demonstrating comparable antitumor efficacy to unmodified strains.

These retargeted MV-Edm derivatives are engineered to bind specifically to tumor cells, which may enhance their therapeutic index and effectiveness in targeting cancerous tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic measles virus retargeting by ligand display. Msaouel, P., Iankov, ID., Allen, C., et al.[2021]

The live attenuated measles virus vaccine effectively infected and destroyed breast cancer cells, particularly showing a strong cytotoxic effect on the AMJ13 cell line, with an IC50 of 3.527, compared to 5.079 for MCF-7 and 9.171 for CAL-51.

The measles virus treatment significantly induced apoptosis in the breast cancer cell lines, suggesting it could be a safe and promising anticancer therapy for breast cancer, especially in cases with functional BRCA1/BRCA2 genes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attenuated measles vaccine strain have potent oncolytic activity against Iraqi patient derived breast cancer cell line. Abdullah, SA., Al-Shammari, AM., Lateef, SA.[2023]

The study demonstrated that an oncolytic measles virus modified to express human granulocyte colony-stimulating factor (MVhGCSF) can enhance the immune response against certain B-cell tumors, particularly in the Raji model, indicating its potential as a cancer treatment.

However, the effectiveness of MVhGCSF varies by tumor type, as it did not show the same enhancement in the Nalm-6 model, highlighting the need for tailored approaches in oncolytic virus therapies based on specific tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Neutrophils in Measles Virus-mediated Oncolysis Differs Between B-cell Malignancies and Is Not Always Enhanced by GCSF. Dey, A., Zhang, Y., Castleton, AZ., et al.[2019]

The engineered measles virus (MV-s-NAP) demonstrated anti-tumor and immunostimulatory effects in breast cancer models, suggesting its potential as an effective treatment for metastatic breast cancer (MBC).

In a safety evaluation using a mouse model, both subcutaneous and intravenous delivery of MV-s-NAP showed no significant toxicity, supporting its safety for use in a planned phase I clinical trial for MBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical safety assessment of MV-s-NAP, a novel oncolytic measles virus strain armed with an H . pylori immunostimulatory bacterial transgene. Viker, KB., Steele, MB., Iankov, ID., et al.[2022]

Intratumoral administration of low doses of the MMR vaccine (measles, mumps, and rubella) has shown promising results in controlling tumors and improving survival in mouse models of liver and colorectal cancer by enhancing the infiltration of effective immune cells like CD8+ T-cells.

The MMR vaccine activates both innate and adaptive immune responses against cancer, suggesting it could be a safe and cost-effective option for cancer immunotherapy, making it accessible to more patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repurposing live attenuated trivalent MMR vaccine as cost-effective cancer immunotherapy. Zhang, Y., Gabere, M., Taylor, MA., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9437807/

Preclinical safety assessment of MV-s-NAP, a novel ... The Helicobacter pylori neutrophil-activating protein (NAP) is responsible for the robust inflammatory reaction in gastroduodenal mucosa during bacterial ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1525001616325370

Expression of Immunomodulatory Neutrophil-activating ... Here, we evaluated the therapeutic efficacy of measles virus (MV) strains engineered to express secretory NAP forms against metastatic breast cancer.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04521764

NCT04521764 | A Vaccine (MV-s-NAP) for the Treatment of ... This phase I trial investigates the side effects and best dose of using a modified measles virus, MV-s-NAP, in treating patients with invasive breast cancer.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22334023/

Expression of immunomodulatory neutrophil-activating ... Here, we evaluated the therapeutic efficacy of measles virus (MV) strains engineered to express secretory NAP forms against metastatic breast cancer.

5. cell.com cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(16)37931-X

490. Measles Virus Encoding H. pylori Neutrophil- ... The anti-tumor activity of attenuated MV strains has been demonstrated in preclinical models of subcutaneous human cancer xenografts, including breast cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04521764

NCT04521764 | A Vaccine (MV-s-NAP) for the Treatment of ... This phase I trial investigates the side effects and best dose of using a modified measles virus, MV-s-NAP, in treating patients with invasive breast cancer ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2329050122001280

Safety study supports clinical development of ... The present study adds to the body of data attesting safety of oncolytic measles virotherapy. Previous early-phase clinical trials have demonstrated safety and ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3903391/

Measles virus expressed Helicobacter pylori neutrophil- ... Expression of immunomodulatory neutrophil-activating protein of Helicobacter pylori enhances the antitumor activity of oncolytic measles virus. Molecular ...