Breast Cancer Vaccine in Combination With Pembrolizumab for Treatment of Persistent, Recurrent, or Metastatic Breast Cancer

NCT04418219 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 20P.020JT 14833
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects of a breast cancer vaccine (SV-BR-1-GM) and how well it works in combination with pembrolizumab for the treatment of breast cancer that is persistent, has come back (recurrent), or has spread to other places in the body (metastatic). Breast cancer vaccine SV-BR-1-GM is a human breast cancer cell line that has been genetically engineered to produce a substance called "GM-CSF" (granulocyte-macrophage colony stimulating factor) which occurs naturally in the body. GM-CSF is normally produced by white blood cells and helps the body develop immunity to disease-causing germs. Immunotherapy with monoclonal antibodies such as pembrolizumab may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Anti-cancer drugs such as cyclophosphamide may help boost the immune response. Interferon alpha 2b may help stimulate the immune system to fight cancer. This trial may help doctors see whether SV-BR-1-GM injections help boost the immune system and/or help control or help shrink breast cancer along with the other drugs that also boost the immune system.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Breast Carcinoma; Prognostic Stage IV Breast Cancer AJCC v8; Recurrent Breast Carcinoma; Refractory Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Toxicity will be determined using the Common Terminology Criteria for Adverse Events (CTCAE v 5.0).

  up to 1 year

• Objective response rate (ORR)

  Will be defined as complete response (CR), partial response (PR) or stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-modified (i)RECIST. The method of Atkinson and Brown will be used to allow for the two-stage design.

  up to 1 year

Secondary Outcomes (9)

• Non-progressive rate

  Up to one year

• Durability of response

  Up to one year

• Delayed type hypersensitivity (DTH) skin tests

  Up to 1 year

• T cell responses to SV-BR-1

  Up to 1 year

• Tumor expression of PD-L1

  Up to 1 year

Study Arms (1)

Treatment (SV-BR-1GM, pembrolizumab)

EXPERIMENTAL

Patients receive cyclophosphamide IV over 1-2 hours on day 1, SV-BR-1-GM ID on day 3, pembrolizumab IV over 30 minutes on day 5, and interferon-alpha-2b ID on days 5 and 7. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Biological: Allogeneic GM-CSF-secreting Breast Cancer Vaccine SV-BR-1-GM; Biological: Pembrolizumab; Biological: Recombinant Interferon Alpha 2b-like Protein; Other: Questionnaire Administration; Other: Quality of Life Assessment

Interventions

Cyclophosphamide DRUG

alkylating agent used in the treatment of several forms of cancer including leukemias, lymphomas and breast cancer.

Treatment (SV-BR-1GM, pembrolizumab)

Allogeneic GM-CSF-secreting Breast Cancer Vaccine SV-BR-1-GM BIOLOGICAL

Breast Cancer Vaccine SV-BR-1-GM, Bria-IMT, GM-CSF Gene-transfected Breast Cancer Vaccine SV-BR-1-GM, SV-BR-1 Breast Cancer Cell Line Vaccine, SV-BR-1-GM, SV-BR-1-GM Vaccine

Treatment (SV-BR-1GM, pembrolizumab)

Pembrolizumab BIOLOGICAL

1374853-91-4, Immunoglobulin G4, Anti-(Human Programmed Cell Death 1); Humanized Mouse Monoclonal (228-L-proline(H10-S\>P))gamma 4 Heavy Chain (134-218'')-disulfide with Humanized Mouse Monoclonal Kappa Light Chain Dimer (226-226'''':229-229'''')-bisdisulfide, Keytruda, Lambrolizumab, MK-3475, PEMBROLIZUMAB, SCH 900475

Treatment (SV-BR-1GM, pembrolizumab)

Recombinant Interferon Alpha 2b-like Protein BIOLOGICAL

Novaferon, Recombinant IFN Alfa-2b-like Protein

Treatment (SV-BR-1GM, pembrolizumab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (SV-BR-1GM, pembrolizumab)

Quality of Life Assessment OTHER

Ancillary studies

Treatment (SV-BR-1GM, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Have evidence of persistent, recurrent, or progressive metastatic breast cancer for which there is no known or established treatment available with curative intent, after failing at least two courses of community standard systemic treatment with chemotherapy (and endocrine therapy, if appropriate)
• Human epidermal growth factor 2 (HER2) positive and estrogen receptor (ER) or progesterone receptor (PR) positive tumors: must be refractory to hormonal therapy (e.g., aromatase inhibitor, tamoxifen or fulvestrant) and previously treated with at least 1 regimen that includes at least two antiHER2 agents (e.g., trastuzumab and pertuzumab)
• ER/PR positive, HER2 negative tumors: must be refractory to hormonal therapy (e.g. aromatase inhibitor, tamoxifen or fulvestrant) and previously treated with at least 2 chemotherapy containing regimens
• HER2 positive and ER/PR negative tumors: must have failed at least 2 regimens including at least two anti-HER2 agents (e.g., trastuzumab and pertuzumab)
• Triple negative tumors (defined as ER \< 1%, PR \< 1% as per American Society of Clinical Oncology College of American Pathologists \[ASCO CAP\] guidelines, HER2/neu 0-1 by immunohistochemistry \[IHC\] or negative by dual in situ hybridization \[ISH\]): Must have failed two other treatment lines including either a taxane and/or atezolizumab. Patients can have had atezolizumab (PD-L1 inhibitor) or PD-1 therapy previously
• Patients will only be eligible for this study if they have at least one human leukocyte antigen (HLA) match:
• HLA-A\*24:02
• HLA-B\*35:08
• HLA-B\*55:01
• HLA-C\*04:01
• HLA-C\*01:02
• HLA-DRB3\*01:01
• HLA-DRB3\*02:02
• Have expected survival of at least 4 months
• Have adequate performance status (Eastern Cooperative Oncology Group \[ECOG\] 0-1)

You may not qualify if:

• Concurrent or recent chemotherapy, radiotherapy, immunotherapy, or general anesthesia/major surgery within 4 weeks
• Patients must have recovered from all known or expected toxicities from previous treatment and passed a treatment-free "washout" period of 3 weeks before starting this program
• If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to enrollment
• Participants must have recovered from all adverse events (AEs) due to previous therapies to =\< grade 1 or baseline
• \* Participants with =\< grade 2 neuropathy and/or alopecia may be eligible
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g, FluMist) are live attenuated vaccines and are not allowed
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
• History of clinical hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-alpha-2b, yeast, beef, or to any components used in the preparation of SV-BR-1-GM
• Has severe hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients
• Proteinuria \>1+ on urinalysis or \>1 gm/24hr
• Left ventricular ejection fraction (LVEF as determined by cardiac echo or multigated acquisition scan \[MUGA\] scan) below the normal limits of the institutions' specific testing range. This assessment may be repeated once at the discretion of the Investigator with the approval of the principal investigator
• New York Heart Association stage 3 or 4 cardiac disease
• A pleural or pericardial effusion of moderate severity or worse
• WOCBP who have a positive urine pregnancy test within 7 days prior to enrollment

Sponsors & Collaborators

• Thomas Jefferson University: lead

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; pembrolizumab; recombinant interferon alpha 2b-like protein

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2020
• First Posted: June 5, 2020
• Study Start: December 21, 2020
• Primary Completion: January 1, 2023
• Study Completion: January 1, 2024
• Last Updated: April 29, 2025

Record last verified: 2025-04

Locations

US (1)