Personalized Vaccine + Checkpoint Inhibitors for Breast Cancer

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

18 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Personalized Vaccine + Checkpoint Inhibitors for Breast Cancer?

Research shows that immune checkpoint inhibitors like pembrolizumab have shown clinical responses in various cancers, including breast cancer, by helping the immune system attack cancer cells. Additionally, early trials of breast cancer vaccines have shown safety and some signs of effectiveness, suggesting that combining these approaches could enhance treatment outcomes. ^{1 2 3 4 5}

What safety data exists for pembrolizumab and ipilimumab in humans?

Pembrolizumab and ipilimumab, used in treating various cancers, have shown some common side effects like fatigue, cough, and nausea. More serious immune-related side effects can include lung inflammation (pneumonitis), liver inflammation (hepatitis), and thyroid issues, but these are less common. Overall, these treatments have been considered safe enough for use in life-threatening conditions like melanoma. ^{6 7 8 9 10}

What makes the Personalized Vaccine + Checkpoint Inhibitors treatment unique for breast cancer?

This treatment is unique because it combines personalized vaccines with immune checkpoint inhibitors, which are drugs that help the immune system recognize and attack cancer cells more effectively. This approach aims to enhance the body's immune response specifically against breast cancer, potentially leading to more durable clinical responses compared to traditional therapies. ^{1 2 11 12 13}

What is the purpose of this trial?

This phase I trial tests the safety, side effects, and best dose of a personalized vaccine (tumor membrane vesicle or TMV vaccine) by itself and in combination with checkpoint inhibitor (pembrolizumab or ipilimumab) in treating patients with triple negative breast cancer. This vaccine is made by taking a piece of patient's triple negative breast cancer to design a vaccine to stimulate the immune system's memory. Patients are treated with the personalized vaccine immunotherapy with or without monoclonal antibodies, such as pembrolizumab and ipilimumab. This approach may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving personalized TMV vaccine with pembrolizumab or ipilimumab may help the immune system attack cancer better and reduce the risk of this breast cancer coming back or growing.

Research Team

Keerthi Gogineni

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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]

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]

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]

References

1. England 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. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Breast cancer immunobiology driving immunotherapy: vaccines and immune checkpoint blockade. [2021]

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

Immune targeting in breast cancer. [2022]

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

Towards a therapeutic breast cancer vaccine: the next steps. [2015]

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

Evaluating Mismatch Repair Status to Screen Clinical Advanced Breast Carcinomas for Immunotherapy: Experience From a Large Academic Institution. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Ipilimumab: first global approval. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

11. England pubmed.ncbi.nlm.nih.gov

Breakthrough concepts in immune-oncology: Cancer vaccines at the bedside. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Influenza vaccination in cancer patients receiving immune checkpoint inhibitors: A systematic review. [2021]

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

Cell-Mediated Immunogenicity of Influenza Vaccination in Patients With Cancer Receiving Immune Checkpoint Inhibitors. [2021]