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.
PRIMARY OBJECTIVES: I. To evaluate the safety of the allogeneic GM-CSF-secreting breast cancer vaccine SV-BR-1-GM (SV-BR-1-GM) regimen when administered in combination with pembrolizumab in patients with human leukocyte antigen (HLA) match. (Phase I) II. To evaluate the overall response rate of the SV-BR1-GM regimen in combination with pembrolizumab. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the non-progressive rate of the SV-BR-1-GM regimen in combination with pembrolizumab. II. To evaluate the duration of response of the SV-BR-1-GM regimen in combination with pembrolizumab. III. To evaluate immune responses elicited by the SV-BR-1-GM regimen when administered in combination with pembrolizumab. IV. To evaluate patient and tumor characteristics that may be predictive of responses to the SV-BR-1-GM regimen when administered in combination with pembrolizumab. V. To evaluate quality of life (QOL) in patients administered the SV-BR-1-GM regimen in combination with pembrolizumab by the Edmonton Symptom Assessment Survey. OUTLINE: Patients receive cyclophosphamide intravenously (IV) over 1-2 hours on day 1, SV-BR-1-GM intradermally (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. After completion of study treatment, patients are followed up at 2-4 weeks and then every 3 months for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
alkylating agent used in the treatment of several forms of cancer including leukemias, lymphomas and breast cancer.
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
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
Novaferon, Recombinant IFN Alfa-2b-like Protein
Ancillary studies
Ancillary studies
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Incidence of adverse events
Toxicity will be determined using the Common Terminology Criteria for Adverse Events (CTCAE v 5.0).
Time frame: 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.
Time frame: up to 1 year
Non-progressive rate
Defined as time to progression of disease, measured by CR, PR or SD per RECIST 1.1 and iRECIST. This will be estimated using the Kaplan-Meier method.
Time frame: Up to one year
Durability of response
Defined in time as time to progressive disease.
Time frame: Up to one year
Delayed type hypersensitivity (DTH) skin tests
Will be evaluated comparing pre-dose with post-dose samples using simple statistical testing (e.g. Student's t-Test).
Time frame: Up to 1 year
T cell responses to SV-BR-1
Will be evaluated comparing pre-dose with post-dose samples using simple statistical testing (e.g. Student's t-Test).
Time frame: Up to 1 year
Tumor expression of PD-L1
Time frame: Up to 1 year
Tumor expression of PD-L2
Time frame: Up to 1 year
Tumor expression of cancer/testis antigens such as PRAME
Time frame: Up to 1 year
Type of breast cancer (estrogen receptor [ER] positive, HER2 positive, triple negative)
Time frame: Up to 1 year
Edmonton Symptom Assessment Survey
Assessment of nine symptoms commonly seen in cancer patients. Patients rate on scale of 0-10 with 0 meaning the symptom is absent and 10 meaning the worst possible severity.
Time frame: Up to 1 year
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