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Personalized Vaccine Immunotherapy in Combination With Checkpoint Inhibitor for Treatment of Triple Negative Breast Cancer

ConditionsAnatomic Stage I Breast Cancer AJCC v8Anatomic Stage IA Breast Cancer AJCC v8Anatomic Stage IB Breast Cancer AJCC v8Anatomic Stage II Breast Cancer AJCC v8Anatomic Stage IIA Breast Cancer AJCC v8Anatomic Stage IIB Breast Cancer AJCC v8Anatomic Stage III Breast Cancer AJCC v8Anatomic Stage IIIA Breast Cancer AJCC v8Anatomic Stage IIIB Breast Cancer AJCC v8Anatomic Stage IIIC Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Early Stage Triple-Negative Breast CarcinomaLocally Advanced Triple-Negative Breast CarcinomaMetastatic Triple-Negative Breast CarcinomaPrognostic Stage I Breast Cancer AJCC v8Prognostic Stage IA Breast Cancer AJCC v8Prognostic Stage IB Breast Cancer AJCC v8Prognostic Stage II Breast Cancer AJCC v8Prognostic Stage IIA Breast Cancer AJCC v8Prognostic Stage IIB Breast Cancer AJCC v8Prognostic Stage III Breast Cancer AJCC v8Prognostic Stage IIIA Breast Cancer AJCC v8Prognostic Stage IIIB Breast Cancer AJCC v8Prognostic Stage IIIC Breast Cancer AJCC v8Prognostic Stage IV Breast Cancer AJCC v8Recurrent Breast CarcinomaUnresectable Triple-Negative Breast Carcinoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorEmory University

About 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information

Must be age >= 18 years

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days prior to tissue consent

Absolute neutrophil count > 1500/mcL (obtained within 14 days prior to vaccine administration)

Disqualifiers

Weight of the tumor tissue is less 1 gram

Clinically significant comorbid conditions such as cardiovascular disease or significant peripheral vascular (e.g., uncontrolled hypertension, myocardial infarction, unstable angina) within 6 months of study entry, serious cardiac arrhythmia requiring medication, and uncontrolled infection

No second malignancy except prior breast cancer or except non-melanomatous skin cancer within the past 5 years

Ongoing or planned systemic anti-cancer therapy or radiation therapy. Last cycle of cytotoxic therapy must be >= 21 days prior to C1D1 of vaccine. Last cycle of checkpoint inhibitor therapy be >= 28 days prior to C1D1 of vaccine. Last dose of radiotherapy must be >= 14 days prior to C1D1 of vaccine

Trial design

Design model

Sequential

Treatments tested in this trial

  • Ipilimumab

    Biological/Vaccine

    Given IV

  • Pembrolizumab

    Biological/Vaccine

    Given IV

  • Vaccine Therapy

    Biological/Vaccine

    Given TMV vaccine ID

Treatment groups

18 Participants
are divided into 3 treatment groups
Group A: Phase Ia (TMV vaccine)Experimental treatment 1 intervention
Group B: Phase Ib Arm A ( TMV vaccine, pembrolizumab)Experimental treatment 2 interventions
Group C: Phase Ib Arm B ( TMV vaccine, ipilimumab)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Incidence of adverse events (Phase Ia)

Safety and tolerability will be assessed by adverse events (AE), vital signs, physical exam findings, clinical laboratory safety assessments and incidence of treatment-emergent AE. AE events will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and will be evaluated by grade and organ class.

Time frame
Up to 2 years
2

Dose limiting toxicity (Phase Ia)

Defined by the occurrence of any grade 3 or greater AEs that are at least possibly related to protocol therapy administration, except for grade 3 injection site reactions that are adequately controlled by medical treatment (e.g. steroid administration) and except for inadequately treated nausea, vomiting, diarrhea, or fever.

Time frame
Up to week 5

Secondary outcomes

1

Immune stimulating activity- T cell activity

Will be measured through analysis of T cell markers in the peripheral blood by comparing immune biomarkers immediately before initial vaccination and after vaccination (weekly at week \[W\]2, W3, W4, W5, W6; 7 days and 12 weeks after final vaccination).

Time frame
Up to 12 weeks after final vaccination
2

Immune stimulating activity- Plasma cytokine/chemokines

Will be measured through analysis of plasma cytokine/chemokine biomarkers in the peripheral blood by comparing immune biomarkers immediately before initial vaccination and after vaccination (weekly at week \[W\]2, W3, W4, W5, W6; 7 days and 12 weeks after final vaccination).

Time frame
Up to 12 weeks after final vaccination
3

Optimal biologic dose

Each dose level will be examined for safety profile sequentially from the lowest dose level by using up to 6 patients/dose level. Once done, the immune stimulating activity (ISA) profile will be examined among dose levels that are determined to be safe. While the dose-response relationship has been examined, the optimal biological dose (OBD) is defined as the lowest dose providing the highest ISA while being safely administered.

Time frame
Up to week 5
4

Recommended phase 2 dose (Phase Ib)

ISA profile, and clinical outcome data will be described and analyzed jointly for TMV vaccine when delivered intradermally in combination with PD-1-inhibitor pembrolizumab or CTLA-4 inhibitor ipilimumab.

Time frame
Up to week 5

Other outcomes

1

PD-L1 expression

PD-L1 expression will be measured by PD-L1 immunohistochemistry (IHC) of the tumor immune-infiltrating cells and tumor cells using 22C3 antibody to assess CPS score. This will be tested on either fresh tissue, or archival tissue if fresh tissue is exhausted for vaccine production.

Time frame
Up to 2 years
2

TIL density

TILS will be measured by the percentage of tumor stroma around the tumor border infiltrated with mononuclear cells.

Time frame
Up to 2 years
3

BRCA 1/2 mutation status

Assess the association of BRCA 1/2 mutation status with the immune stimulating activity of tumor membrane vesicle (TMV) vaccine when administered as monotherapy and in combination with checkpoint inhibitor therapy

Time frame
Up to 2 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Emory University

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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