Clinical Trials /

PVX-410 Vaccine Plus Pembrolizumab in HLA-A2+ Metastatic Triple Negative Breast Cancer

NCT03362060

Description:

This research study is studying immunotherapy as a possible treatment for metastatic Triple Negative Breast Cancer (TNBC) in participants who are HLA-A2+. The drugs involved in this study are: - PVX-410 - Pembrolizumab - Hiltonol - Montanide

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PVX-410 Vaccine Plus Pembrolizumab in HLA-A2+ Metastatic Triple Negative Breast Cancer
  • Official Title: A Phase 1b Study of Safety and Immune Response to PVX-410 Vaccine Alone and in Combination With Pembrolizumab in HLA-A2+ Patients With Metastatic Triple Negative Breast Cancer (TNBC)

Clinical Trial IDs

  • ORG STUDY ID: 17-328
  • NCT ID: NCT03362060

Conditions

  • Triple Negative Breast Cancer
  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaPVX-410
PVX-410PVX-410

Purpose

This research study is studying immunotherapy as a possible treatment for metastatic Triple Negative Breast Cancer (TNBC) in participants who are HLA-A2+. The drugs involved in this study are: - PVX-410 - Pembrolizumab - Hiltonol - Montanide

Detailed Description

      This research study is a Phase Ib clinical trial, which tests the safety of an
      investigational drug combination and also tries to better understand how the investigational
      intervention affects the body.

      "Investigational" means that the FDA (the U.S. Food and Drug Administration) has not approved
      the combination of PVX-410 and pembrolizumab as a treatment regimen for this specific
      disease.

      The FDA has not approved PVX-410 as a treatment for any disease. PVX-410 is a type of vaccine
      that may help the immune system stimulate immunity against the cancer cells.

      The FDA has not approved pembrolizumab for this specific disease but it has been approved in
      the United Sates for other types of cancer.

      Pembrolizumab is a drug that may treat cancer by working with the immune system. The immune
      system is the body's natural defense against disease. The immune system sends types of cells
      throughout the body to detect and fight infections and diseases, including cancer. For some
      types of cancer, the immune cells do not work as they should and are prevented from attacking
      the tumors. Pembrolizumab is thought to work by blocking a protein in the cells called
      Programmed Death-1 (PD-1), which then allows these cells and other parts of the immune system
      to attack tumors.

      In this research study, the investigators are studying the body's immune response to the
      PVX-410 study vaccine in combination with pembrolizumab. This study will help researchers
      understand if the vaccine and pembrolizumab can work together to help the body's immune
      system recognize and treat triple negative breast cancer. The investigators are also studying
      the safety of the PVX-410 together with the pembrolizumab
    

Trial Arms

NameTypeDescriptionInterventions
PVX-410ExperimentalPVX-410 vaccine at W0, 1, 2, 3, 4, and 5 followed by booster PVX-410 vaccine doses at W10 and 28 Pembrolizumab will be administered every 3 weeks intravenously starting with week 1
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to provide written informed consent for the study.

          -  Female aged ≥18 years on the day of signing informed consent.

          -  HLA A2+ by deoxyribonucleic acid (DNA) sequence analysis (by history with
             documentation or as part of this study).

          -  Histopathological diagnosis of metastatic or inoperable locally advanced TNBC that
             meets the following criteria:

             --Triple negative defined as Estrogen Receptor (ER)<1%, Progesterone Receptor (PR)<1%,
             and Human Epidermal Growth Factor Receptor 2 (HER2) negative according to American
             Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
             by local testing according to institutional standards.

          -  For tumors with equivocal interpretation of receptor status (e.g., ER/PR ≥1% "weak" or
             "faint" staining), the Principal Investigator will have final determination of
             triple-negative status. For tumors with discrepant receptor results between 2 or more
             biopsies (including metastatic and/or early stage biopsies), the Principal
             Investigator will have final determination of triple negative status, but in general
             the most recent biopsy can be used for eligibility purposes. If receptor testing is
             not available on a metastatic biopsy, the primary tumor test result is acceptable.

          -  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 without a documented metastatic biopsy, provided the patient has a
             prior diagnosis of TNBC that otherwise meets the eligibility criteria.

             --Ductal, lobular, mixed, or metaplastic histology.

          -  Measurable disease, as determined by RECIST 1.1.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Appendix
             section 16.1)

          -  At least one line of prior systemic therapy for metastatic or recurrent breast cancer
             (there is no limit to the number of prior therapies).

          -  Adequate normal organ and marrow function within 10 days of planned treatment
             initiation, as defined below:

        Hematologic

          -  Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin dependency
             (within 7 days of assessment)

          -  Absolute neutrophil count (ANC) ≥1.5x10^9/L (≥1500 per mm3)

          -  Platelet count ≥100x109/L (≥100,000 per mm3) Renal

          -  Serum creatinine ≤1.5 x the upper limit of normal (ULN) OR measured or calculated
             creatinine clearance ≥60 mL/min for patients with creatinine levels >1.5 x
             institutional Upper Limit of Normal (ULN) (calculated per institutional standard).
             (Glomerular filtration rate can be used in place of creatinine or creatinine
             clearance.) Hepatic

          -  Serum bilirubin ≤1.5 x institutional ULN OR direct bilirubin ≤ ULN for patients with
             total bilirubin levels >1.5 x ULN

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 x institutional
             ULN OR ≤5 x ULN for patients with known liver metastases.

          -  Albumin ≥2.5 mg/dL Coagulation

          -  International normalized ratio (INR) or prothrombin time (PT) ≤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.

          -  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 Other

          -  Lactate Dehydrogenase (LDH) ≤1.5 x institutional ULN

               -  Willing to provide archived tissue for correlative studies. If no archived sample
                  is available the patient will still be eligible.

               -  Negative virology/serology for human immunodeficiency virus (HIV)-1, HIV-2,
                  hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) DNA.

               -  Either of non-reproductive potential (i.e., post-menopausal by history of age ≥50
                  years old and no menses for ≥1 year without an alternative medical cause; OR
                  history of hysterectomy, history of bilateral tubal ligation, or history of
                  bilateral oophorectomy) OR must have a negative urine or serum pregnancy within
                  72 hours prior to receiving the first dose of study treatment. If the urine test
                  is positive or cannot be confirmed as negative, a serum pregnancy test will be
                  required.

               -  If of childbearing potential (i.e., does not meet criteria for non-reproductive
                  potential above), willing to use 2 methods of birth control, or be surgically
                  sterile, or abstain from heterosexual activity for the course of the study
                  through 120 days after the last dose of study treatment

               -  Willing and able to comply with the protocol for the duration of the study
                  including undergoing treatment and scheduled visits and examinations, including
                  follow-up

        Exclusion Criteria:

          -  Currently participating and receiving study therapy or has participated in a study of
             an investigational agent and received study therapy or used an investigational device
             within 4 weeks of the first dose of study treatment.

          -  Previous enrollment in the present study.

          -  Mucinous or tubal histology or other good prognosis histology.

          -  Known hypersensitivity to any component of PVX-410, Hiltonol®, Montanide,
             pembrolizumab, or excipients.

          -  Receipt of the last dose or treatment of anti-cancer chemotherapy, radiotherapy,
             surgery, endocrine therapy, targeted therapy, biologic therapy, or tumor embolization
             ≤2 weeks (4 weeks for any monoclonal Antibody (mAb), 6 weeks for nitrosoureas or
             mitomycin C) prior to first dose of study treatment, or has not recovered (i.e., to
             ≤Grade 1 or Baseline) from clinically significant Adverse Events (AEs) due to these
             previously administered agents.

               -  Patients with ≤Grade 2 neuropathy are an exception to this criterion and may
                  qualify for the study.

               -  Subjects with other irreversible toxicity (e.g., hearing loss) or reversible
                  toxicity (e.g. alopecia) that is not reasonably expected to be exacerbated by the
                  investigational product and is not expected to interfere with study participation
                  may be included.

               -  If patient received major surgery, they must have recovered adequately from the
                  toxicity and/or complications from the intervention prior to starting therapy.

          -  Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

          -  Received a live vaccine within 30 days of planned start of study therapy.

             --Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.

          -  Ongoing or planned systemic anti-cancer therapy or radiation therapy.

          -  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.

          -  Known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          -  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.

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial.

          -  History or current evidence of any other condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the patient's
             participation for the full duration of the study, or is not in the best interest of
             the patient to participate, in the opinion of the treating investigator
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Immune Response following treatment with PVX-410 in combination with pembrolizumab
Time Frame:3 years
Safety Issue:
Description:The fold activation of T cells from blood of treated patients at week 10 compared to baseline

Secondary Outcome Measures

Measure:Late Immune response after treatment with PVX-410 and pembrolizumab
Time Frame:3 years
Safety Issue:
Description:The fold activation of T cells from blood of treated patients at week 28 compared to baseline.
Measure:Incidence of treatment emergent adverse events (safety and tolerability) of PVX-410 in combination with pembrolizumab
Time Frame:3 years
Safety Issue:
Description:Number of patients who develop treatment emergent adverse events according to the Common Toxicity Criteria of Adverse Events (CTCAE) version 4.0
Measure:Progression Free Survival
Time Frame:3 years
Safety Issue:
Description:The median time from study enrollment to disease progression of all treated participants.
Measure:Overall Survival
Time Frame:3 years
Safety Issue:
Description:The median time from study enrollment of all participants until death of all treated participants.
Measure:Response rate
Time Frame:3 years
Safety Issue:
Description:The rate of RECIST defined responses (complete and partial response).
Measure:Disease Control Rate
Time Frame:3 years
Safety Issue:
Description:The sum of the rates of best response (Complete Response, Partial Response, and Stable Disease).
Measure:Clinical Benefit Rate
Time Frame:3 years
Safety Issue:
Description:The sum of the RECIST defined rates of Complete Response, Partial Response, and Stable Disease.
Measure:Duration of response
Time Frame:3 years
Safety Issue:
Description:The median time of the response from time of first response to time of progression for all responding treated participants.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Triple Negative Breast Cancer
  • Vaccine
  • Immunotherapy
  • PD-1 Inhibitor
  • Metastatic Breast Cancer

Last Updated

January 25, 2018