Clinical Trials /

A Breast Cancer Vaccine (SV-BR-1-GM) in Combination With Pembrolizumab for the Treatment of Persistent, Recurrent, or Metastatic Breast Cancer

NCT04418219

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Breast Cancer Vaccine (SV-BR-1-GM) in Combination With Pembrolizumab for the Treatment of Persistent, Recurrent, or Metastatic Breast Cancer
  • Official Title: A Phase I/II Study of the SV-BR-1-GM Regimen in HLA Matched Metastatic Breast Cancer Patients in Combination With Pembrolizumab

Clinical Trial IDs

  • ORG STUDY ID: 20P.020
  • NCT ID: NCT04418219

Conditions

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

Interventions

DrugSynonymsArms
CyclophosphamideTreatment (SV-BR-1GM, pembrolizumab)
Allogeneic GM-CSF-secreting Breast Cancer Vaccine SV-BR-1-GMTreatment (SV-BR-1GM, pembrolizumab)
PembrolizumabTreatment (SV-BR-1GM, pembrolizumab)
Recombinant Interferon Alpha 2b-like ProteinTreatment (SV-BR-1GM, pembrolizumab)

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (SV-BR-1GM, pembrolizumab)ExperimentalPatients 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.
  • Cyclophosphamide
  • Allogeneic GM-CSF-secreting Breast Cancer Vaccine SV-BR-1-GM
  • Pembrolizumab
  • Recombinant Interferon Alpha 2b-like Protein

Eligibility Criteria

        Inclusion Criteria:

          -  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)

          -  A female participant is eligible to participate if she is not pregnant, not
             breastfeeding, and at least one of the following conditions applies:

               -  Not a woman of childbearing potential (WOCBP) defined as spontaneous cessation of
                  menstrual cycle for at least 12 months or surgical history of hysterectomy or
                  bilateral salpingoopherectomy OR

               -  A WOCBP who agrees to take appropriate precautions to avoid becoming pregnant
                  during the treatment period and for at least 90 days plus 30 days (a menstruation
                  cycle) for study treatments with risk of genotoxicity after the last dose of
                  study treatment

          -  The participant (or legally acceptable representative if applicable) provides written
             informed consent for the trial

          -  Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)
             1.1. Lesions situated in a previously irradiated area are considered measurable if
             progression has been demonstrated in such lesions

          -  If any brain metastases, must have had prior radiation therapy for brain metastases

          -  Systemic glucocorticoids for any purpose other than to modulate symptoms from an event
             of clinical interest of suspected immunologic etiology are allowed. The use of
             physiologic doses of corticosteroids may be approved after consultation with the
             principal investigator

          -  Absolute neutrophil count (ANC) >= 1500/uL (collected within 14 days prior to the
             start of study treatment)

          -  Platelets >= 100,000/uL (collected within 14 days prior to the start of study
             treatment)

          -  Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (collected within 14 days prior to the start
             of study treatment)

             * Criteria must be met without erythropoietin dependency and without packed red blood
             cell (pRBC) transfusion within last 2 weeks

          -  Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine
             clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or
             creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5
             x institutional ULN (collected within 14 days prior to the start of study treatment)

             * Creatinine clearance (CrCl) should be calculated per institutional standard

          -  Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total
             bilirubin levels > 1.5 ULN

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase) [[SGOT])
             and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase) [[SGPT]) =<
             2.5 x ULN (=< 5 x ULN for participants with liver metastases) (collected within 14
             days prior to the start of study treatment)

          -  International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless
             participant is receiving anticoagulant therapy as long as PT or activated partial
             thromboplastin time (aPTT) is within therapeutic range of intended use of
             anticoagulants (collected within 14 days prior to the start of study treatment)

          -  Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is
             receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of
             intended use of anticoagulants (collected within 14 days prior to the start of study
             treatment)

        Exclusion Criteria:

          -  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

             * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
             test will be required

          -  Women who are pregnant or nursing

          -  Patients with concurrent second malignancy. Persons with previous malignancies
             effectively treated and not requiring treatment for > 24 months are eligible, provided
             there is unambiguous documentation that current local recurrence or metastatic site
             represents recurrence of the primary breast malignancy

          -  Patients who are human immunodeficiency virus (HIV) positive (by self-report) or have
             clinical or laboratory features indicative of acquired immunodeficiency syndrome
             (AIDS)

          -  Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]
             reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA] is
             detected) infection

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis

          -  Has an active infection requiring systemic therapy

          -  Has 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, etc.) is not considered a
             form of systemic treatment

          -  Patients who require systemic steroids at doses > 10 mg daily of prednisone or
             equivalent or any immunosuppressive drugs. Beta-blocker therapy, while not
             exclusionary, is discouraged and alternatives should be sought if possible. The
             beta-blocker might compromise use of epinephrine for the rare possibility of
             anaphylaxis

          -  Patients with a history of colitis

          -  Patients with severe psychiatric (e.g., schizophrenia, bipolar, or borderline
             personality disorder) or other clinically progressive major medical problems, unless
             approved by the principal investigator

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator

          -  Patients may not be on a concurrent treatment clinical trial, unless approved by
             principal investigator
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:up to 1 year
Safety Issue:
Description:Toxicity will be determined using the Common Terminology Criteria for Adverse Events (CTCAE v 5.0).

Secondary Outcome Measures

Measure:Non-progressive rate
Time Frame:Up to one year
Safety Issue:
Description: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.
Measure:Durability of response
Time Frame:Up to one year
Safety Issue:
Description:Defined in time as time to progressive disease.
Measure:Delayed type hypersensitivity (DTH) skin tests
Time Frame:Up to 1 year
Safety Issue:
Description:Will be evaluated comparing pre-dose with post-dose samples using simple statistical testing (e.g. Student's t-Test).
Measure:T cell responses to SV-BR-1
Time Frame:Up to 1 year
Safety Issue:
Description:Will be evaluated comparing pre-dose with post-dose samples using simple statistical testing (e.g. Student's t-Test).
Measure:Tumor expression of PD-L1, PD-L2 and cancer/testis antigens such as PRAME
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Type of breast cancer (estrogen receptor [ER] positive, HER2 positive, triple negative)
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Edmonton Symptom Assessment Survey
Time Frame:Up to 1 year
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Thomas Jefferson University

Last Updated

June 3, 2020