Personalized Vaccine + Checkpoint Inhibitors for Breast Cancer

Not yet recruiting at 3 trial locations

Overseen By Keerthi Gogineni, MD, MSHP

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Cardiovascular disease, CNS metastases, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 25

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new personalized vaccine for individuals with triple negative breast cancer. The vaccine uses a piece of the patient’s own tumor to help the immune system recognize and attack the cancer. The trial will evaluate the vaccine's effectiveness alone and in combination with checkpoint inhibitors, such as Ipilimumab (Yervoy) and Pembrolizumab (KEYTRUDA or MK-3475), which can enhance the immune response against cancer. This trial suits those with triple negative breast cancer that is advanced, metastatic, or early-stage, who have completed initial treatments like surgery or chemotherapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new personalized vaccine.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, ongoing or planned systemic anti-cancer therapy or radiation therapy must be stopped at least 21 to 28 days before starting the trial treatment.

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

Research has shown that the personalized TMV vaccine is generally well-tolerated when used alone. In earlier studies, most patients exhibited a strong immune response, and many remained cancer-free for years. Reports indicate that the vaccine did not cause major side effects.

When combined with pembrolizumab, a drug already used for some cancers, the safety data appears promising. Pembrolizumab is a standard treatment for early-stage breast cancer, indicating it is generally safe. Another study found that using pembrolizumab with other treatments did not result in more significant side effects.

For the combination of the TMV vaccine and ipilimumab, the safety information is less clear. However, ipilimumab is an approved treatment for other cancers, suggesting it has a known safety profile. This trial aims to further assess its safety when used with the TMV vaccine.

This trial is a Phase 1 study, focusing on safety and determining the best dose. The treatment is in early safety testing, and more data is being collected to confirm its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for breast cancer, which typically include surgery, chemotherapy, and radiation, the combination of the TMV vaccine with checkpoint inhibitors like pembrolizumab and ipilimumab offers a fresh approach by harnessing the body’s immune system to fight cancer. The TMV vaccine is designed to personalize the immune response against tumor cells, potentially leading to more targeted and effective treatment. Researchers are excited about these treatments because they represent a shift from traditional methods to immunotherapy, which could result in fewer side effects and improved outcomes for patients. Additionally, pembrolizumab and ipilimumab are known for their ability to unleash the immune system's T-cells, offering a novel mechanism of action that differs from conventional therapies.

What evidence suggests that this trial's treatments could be effective for triple negative breast cancer?

Research shows that pembrolizumab, one of the treatments in this trial, may effectively treat triple-negative breast cancer when combined with other therapies. The KEYNOTE-522 trial found that patients who received pembrolizumab with chemotherapy had better survival rates without cancer events compared to those who received only chemotherapy.

In this trial, some participants will receive the TMV vaccine, made specifically from a patient's tumor, which has been shown to boost the immune system and potentially help the body fight cancer more effectively. Other participants will receive the TMV vaccine combined with ipilimumab. Studies on using the TMV vaccine with ipilimumab have shown longer survival and less cancer spread in models of triple-negative breast cancer. This suggests that these treatments together might help the immune system find and attack cancer cells. Overall, early research suggests these treatments could effectively manage triple-negative breast cancer by using the body's own defenses. ^{4 6 7 8 9}

Who Is on the Research Team?

Keerthi Gogineni

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with triple negative breast cancer. Participants should be suitable to receive a vaccine made from their own tumor cells, combined with immune-boosting drugs called checkpoint inhibitors. Specific eligibility details are not provided but typically include factors like health status and prior treatments.

Inclusion Criteria

Bilirubin =< 1.5 X ULN (except in participants with documented Gilbert's disease, who must have a total bilirubin =< 3.0 mg/dL) (obtained within 14 days prior to vaccine administration)

I am willing and able to follow the study's schedule completely.

My early stage TNBC will be analyzed from tissue taken during my surgery.

Exclusion Criteria

My tumor weighs less than 1 gram.

I haven't had any cancer except breast cancer or skin cancer that's not melanoma in the last 5 years.

I haven't had cancer treatments like chemotherapy, immunotherapy, or radiation within the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ia Treatment

Patients receive TMV vaccine intradermally at weeks 1, 3, and 5 in the absence of disease progression or unacceptable toxicity.

5 weeks

3 visits (in-person)

Phase Ib Treatment - Arm A

Patients receive TMV vaccine intradermally at weeks 1, 3, and 5 and pembrolizumab intravenously on day 1, repeating every 21 days for 6-9 cycles.

18-27 weeks

6-9 visits (in-person)

Phase Ib Treatment - Arm B

Patients receive TMV vaccine intradermally at weeks 1, 3, and 5 and ipilimumab intravenously on day 1, repeating every 21 days for 4 cycles.

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion every 12 weeks for up to 2 years.

Up to 2 years

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Pembrolizumab
• TMV Vaccine

Trial Overview

The trial is testing the safety and optimal dose of a personalized vaccine therapy alongside checkpoint inhibitors (pembrolizumab or ipilimumab). The goal is to see if this combination can better stimulate the immune system to attack breast cancer cells and prevent cancer growth or recurrence.

How Is the Trial Designed?

Group I: Phase Ib Arm B ( TMV vaccine, ipilimumab) Experimental Treatment 2 Interventions

Patients receive TMV vaccine ID at weeks 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Patients also receive ipilimumab IV on day 1. Treatment with ipilimumab repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Phase Ib Arm A ( TMV vaccine, pembrolizumab) Experimental Treatment 2 Interventions

Patients receive TMV vaccine ID at weeks 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV on day 1. Treatment with pembrolizumab repeats every 21 days for 6-9 cycles in the absence of disease progression or unacceptable toxicity.

Group III: Phase Ia (TMV vaccine) Experimental Treatment 1 Intervention

Patients receive TMV vaccine ID at weeks 1, 3, and 5 in the absence of disease progression or unacceptable toxicity.

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Ipilimumab (Yervoy®) is an approved monoclonal antibody for treating malignant melanoma by blocking the CTLA-4 protein, which enhances T-cell responses against tumor cells, showing its efficacy in cancer immunotherapy.

Currently, ipilimumab is also being tested in phase III trials for prostate cancer and phase II trials for non-small cell lung cancer, indicating its potential for broader applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: first global approval. Cameron, F., Whiteside, G., Perry, C.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In patients with hormone receptor-positive metastatic breast cancer, higher levels of specific immune cells (effector memory CD8+ and CD4+ T cells) before treatment were associated with better responses to the combination therapy of palbociclib, pembrolizumab, and letrozole, compared to those receiving only pembrolizumab and letrozole.

The combination therapy also led to significant changes in myeloid cell composition, including increased mature dendritic cells and decreased classical monocytes, which may enhance the immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer. Egelston, C., Guo, W., Yost, S., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Influenza vaccination in cancer patients receiving immune checkpoint inhibitors (ICIs) is safe, with no severe vaccination-related toxicities reported and a low incidence of immune-related adverse events (28.9% overall, 7.5% for grade 3-4).

The vaccination appears to be effective, as seven out of eight studies indicated positive efficacy outcomes, suggesting that it can be beneficial for this patient population, especially during the COVID-19 pandemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccination in cancer patients receiving immune checkpoint inhibitors: A systematic review. Spagnolo, F., Boutros, A., Croce, E., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8641616/

Tumor membrane-based vaccine immunotherapy in ...

In the 4T1 TNBC breast cancer model, TMV vaccine/anti-CTLA-4 mAb combination therapy resulted in increased overall survival, reduced lung metastasis, as well ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12394260/

A systematic review of the efficacy of cancer vaccines in ...

The primary outcome was safety, while secondary outcomes included PFS and peptide-specific immune induction. Main characteristics are presented ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0264410X06007079

TMV-peptide fusion vaccines induce cell-mediated immune ...

In this study we explore the ability of a plant virus, Tobacco mosaic virus (TMV), to stimulate cellular immunity by interacting directly with immune cells.

4.

siteman.wustl.edu

siteman.wustl.edu/vaccine-shows-promise-against-aggressive-breast-cancer/

Vaccine Shows Promise Against Aggressive Breast Cancer

Following treatment, 14 of 18 patients showed immune responses to the vaccine and, after three years, 16 patients remained cancer-free. While ...

5.

mdpi.com

mdpi.com/2076-393X/8/2/182

Tumor Membrane Vesicle Vaccine Augments the Efficacy ...

Our data show a significant decrease in the tumor size in TMV vaccine plus anti-PD-1 mAb combination treatment group compared to the PBS control group. This ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/32530786/

Tumor membrane-based vaccine immunotherapy in ... - PubMed

These results suggest TMV vaccine immunotherapy as a potential enhancer of immune checkpoint inhibitor therapies for metastatic triple-negative ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3426870/

Tobacco Mosaic Virus as a New Carrier for Tumor ...

T/Tn antigen vaccine is effective and safe in preventing recurrence of advanced breast carcinoma. Cancer Detect Prev. 1995;19:374–380. [PubMed] [Google ...

8.

newsroom.clevelandclinic.org

newsroom.clevelandclinic.org/2024/11/08/cleveland-clinic-announces-updated-findings-in-preventive-breast-cancer-vaccine-study

Cleveland Clinic Announces Updated Breast Cancer ...

The study team found that the investigational vaccine was generally well tolerated and produced an immune response in most patients. The team ...

9.

withpower.com

withpower.com/trial/phase-1-carcinoma-5-2024-f5cf8

Personalized Vaccine + Checkpoint Inhibitors for Breast ...

Giving personalized TMV vaccine with pembrolizumab or ipilimumab may help the immune system attack cancer better and reduce the risk of this breast cancer ...