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

NCT06324240 | Recruiting Phase 1 DMC FDA Drug

• 5 other identifiers: STUDY00004185NCI-2022-01950WINSHIP5522-22P30CA138292R44CA257278
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Early Stage Triple-Negative Breast Carcinoma; Locally Advanced Triple-Negative Breast Carcinoma; Metastatic Triple-Negative Breast Carcinoma; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Recurrent Breast Carcinoma; Unresectable Triple-Negative Breast Carcinoma; Anatomic Stage I Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 2 years

• 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.

  Up to week 5

Secondary Outcomes (8)

• Immune stimulating activity- T cell activity

  Up to 12 weeks after final vaccination

• Immune stimulating activity- Plasma cytokine/chemokines

  Up to 12 weeks after final vaccination

• Optimal biologic dose

  Up to week 5

• Recommended phase 2 dose (Phase Ib)

  Up to week 5

• Disease control rate

  Up to 2 years

Other Outcomes (3)

• PD-L1 expression

  Up to 2 years

• TIL density

  Up to 2 years

• BRCA 1/2 mutation status

  Up to 2 years

Study Arms (3)

Phase Ia (TMV vaccine)

EXPERIMENTAL

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

Biological: Vaccine Therapy

Phase Ib Arm A ( TMV vaccine, pembrolizumab)

EXPERIMENTAL

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.

Biological: Pembrolizumab; Biological: Vaccine Therapy

Phase Ib Arm B ( TMV vaccine, ipilimumab)

EXPERIMENTAL

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.

Biological: Ipilimumab; Biological: Vaccine Therapy

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Phase Ib Arm B ( TMV vaccine, ipilimumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, Keytruda, Lambrolizumab, MK-3475, Pembrolizumab Biosimilar BCD-201, SCH 900475

Phase Ib Arm A ( TMV vaccine, pembrolizumab)

Vaccine Therapy BIOLOGICAL

Given TMV vaccine ID

Phase Ia (TMV vaccine); Phase Ib Arm A ( TMV vaccine, pembrolizumab); Phase Ib Arm B ( TMV vaccine, ipilimumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Absolute lymphocyte count \>= 600 cells/µl (obtained within 14 days prior to vaccine administration)
• Platelets \> 100,000 mm (obtained within 14 days prior to vaccine administration)
• Hemoglobin \> 9.0 g/dL (obtained within 14 days prior to vaccine administration) (NOTE: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \> 9.0g/dl is acceptable)
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance \>= 60 mL/min using Cockcroft-Gault equation for patients with creatinine levels \> 1.5 x institutional ULN (obtained within 14 days prior to vaccine administration)
• Total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< 1 x ULN (obtained within 14 days prior to vaccine administration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN unless liver metastases are present, in which case they must be =\< 5 x ULN (obtained within 14 days prior to vaccine administration)
• 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)
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (obtained within 14 days prior to vaccine administration)
• Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (obtained within 14 days prior to vaccine administration)
• TNBC as defined by estrogen receptor (ER)/progesterone receptor (PR) =\< 10% if Allred =\< 3; Her2/neu negative as defined by scores of 0 or 1+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of \< 2.0 or \< 6 Her2 copies per cell
• Patients with metastatic or inoperable locally advanced disease: Metastatic or inoperable locally advanced disease is defined as either histologically confirmed metastatic breast cancer by biopsy; or locally advanced breast cancer that, in the opinion of the treating physician, is not amenable to curative intent surgical resection; or, radiological or clinical evidence suggestive and supportive of metastatic disease

You may not qualify if:

• 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
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment
• Has a known history of active tuberculosis (Bacillus Tuberculosis)
• History of allogeneic organ transplant
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for management of brain metastases for at least 7 days prior to study treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
• Known history of non-infectious pneumonitis that required steroids or any evidence of active pneumonitis
• Failure to recover from grade 3 or 4 toxicity from previous treatment
• For the combination cohort: prior grade 4 immune-related adverse events due to previous ICI. Patients who experienced grade 2 or 3 toxicity with prior ICI therapy may enroll if toxicity reverted to =\< grade 1

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Grady Health System

Atlanta, Georgia, 30303, United States

RECRUITING

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

Ipilimumab; CTLA-4 Antigen; pembrolizumab; Immunotherapy, Active

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Keerthi Gogineni, MD, MSHP

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Keerthi Gogineni, MD, MSHP

CONTACT

404-778-1900; keerthi.gogineni@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 15, 2024
• First Posted: March 21, 2024
• Study Start: December 2, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 26, 2026

Record last verified: 2025-12

Locations

US (4)