Clinical Trial 21024

• Overview

  Study Title:

  A Phase IIa Study of Dendritic Cell Vaccines against HER2/HER3 and Pembrolizumab in Patients with Asymptomatic Brain Metastasis from Triple Negative Breast Cancer (TNBC) or HER2+ Breast Cancer (HER2+BC)

  Summary:

  This phase IIa trial studies how well dendritic cell vaccines against Her2/Her3 and pembrolizumab work for the treatment of triple negative breast cancer or HER2+ breast cancer that has spread to the brain (brain metastasis). Dendritic cell vaccines work by boosting the immune system (a system in the body that protect against infection) to recognize and destroy the cancer cells. . Pembrolizumab is an "immune checkpoint inhibitor" which is designed to either "unleash" or "enhance" the cancer immune responses that already exist by either blocking inhibitory molecules" or by activating stimulatory molecules. Giving dendritic cell vaccines and pembrolizumab may shrink the cancer.

  Objective:

  Primary Objective: - Best Overall CNS response rate per RANO-BM (1) Secondary Objectives: - Volumetric quantification of brain metastases - The non-CNS (i.e. of systemic disease) response rate as per RECIST 1.1 - The median CNS, non-CNS and overall Progression Free Survival (PFS). - The median Overall Survival (OS). - The safety of this regimen. - The proportion of patients not requiring retreatment for their brain metastasis at 6 months since the first dose of anti-HER2/3 vaccine. - Rate of failure of irradiated lesions.

• Treatments

  Therapies:

  Chemotherapy (NOS); Immunotherapy

  Medications:

  DC1 Vaccine (); Pembrolizumab (Keytruda)

• Inclusion Criteria

  Inclusion Criteria:
  • Female participant is eligible to participate if not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or A WOCBP who agrees to follow contraceptive guidance.
  • WOCBP must agree to use acceptable birth control methods for the duration of the study and until persistence of the study drug is no longer detected in the peripheral blood:this may be a period of several years. Methods for acceptable birth control defined in protocol.
  • Negative serum and highly sensitive urine pregnancy test(s): i) within 72 hours prior to study allocation; ii) following initiation of treatment, pregnancy testing will be performed for WOCBP and interpreted prior to every cycle of pembrolizumab iii) at the EOT Assessment; and iv) whenever pregnancy is otherwise suspected.
  • Histologically or cytologically confirmed diagnosis of triple negative breast cancer (TNBC) (estrogen receptor [ER] == 2.0, and the HER2 copy number signals/cell is >= 4 (ii) Definitive diagnosis will be rendered pending further workup in the following instances: (a) If the HER2/CEP17 ratio is >= 2.0 and an average HER2 copy number is = 6.0 signals/cell positive - if confirmed on retesting (c) If the HER2/CEP17 ratio is = 4.0 and > Measurable brain disease as per RANO-BM criteria modified to include the cutoff point of 0.5 cm or higher. Have at least one untreated brain metastasis approved by a research team that meets the size requirements per protocol.
  • Any brain metastasis >= 3.0 cm or causing symptoms must have previously been treated with local therapy (i.e. radiation or surgical resection, as clinically appropriate) prior to study enrollment. Any lesion present at the time of whole brain radiation therapy (WBRT) or included in the stereotactic radiotherapy field (or within 5 mm of the treated lesion) will NOT be considered evaluable unless it is new or documented to have progressed since treatment
  • Stereotactic radiosurgery (SRS) and/or prior radiotherapy is permitted >=2 weeks prior to initial Dendritic Cell (DC) vaccine dose (leaving one or more lesions which are not radiated and will be used as target lesions) but a follow up brain MRI should be obtained prior to dendritic cell (DC) vaccine to determine stability of the lesions. An interval of at least 4 weeks after the end of whole brain radiation or for any surgical resection of brain lesions is permitted ; an interval of at least 4 weeks or 5 half-lives (whichever is sorter) after the last cytotoxic, targeted, immunotherapeutic or investigational agent is permitted (prior to the start of DC vaccine). Previous whole brain radiation is allowed if patient has been diagnosed with recurrent, progressive brain metastasis. Previously irradiated lesions would be considered non-target lesions. Previously resected lesions or those treated with SRS would be considered nontarget lesions. There is no limitation on prior local therapies to other lesions.
  • If patient received major surgery, must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Add'l criteria apply

• Exclusion Criteria

  Exclusion Criteria:
  • Any condition which might confound the results of the study, interfere with the subject's participation for full participation (for the full duration of the study) or in the Investigator's opinion deems the participant an unsuitable candidate for the study
  • Symptomatic brain metastases. Any neurologic symptoms present must have resolved with local therapy by the time of administration of study drugs
  • May not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of DC vaccine treatment
  • Has had prior chemotherapy or targeted small molecule therapy (except treatment mentioned in inclusion criteria 17) within 4 weeks or 5 half-lives (whichever is sooner) prior to start of treatment (first DC vaccine) or who has not recovered (i.e., => Rapidly progressing systemic disease which might interfere with completion of all the vaccine doses
  • 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 and is allowed
  • History of allogenic tissue/solid organ transplantation
  • Has an active infection requiring systemic therapy which in the investigator's opinion will increase risk to the patient
  • Has known active hepatitis B or hepatitis C infection (Testing is not mandatory)
  • Has known immunosuppressive disease (e.g. human immunodeficiency virus [HIV], acquired immunodeficiency syndrome [AIDS] or other immune depressing disease). Testing is not mandatory
  • Has received a blood transfusion in the two weeks prior to leukapheresis
  • Pregnant or actively nursing (females who agree to stop nursing would be eligible) participants
  • Unwilling or unable to follow protocol requirements
  • Brain lesion size with significant midline shift or obstructive hydrocephalus
  • The use of corticosteroids to control cerebral edema or treat neurologic symptoms will not be allowed unless at a low dose, not to exceed 10 mg of prednisone (or equivalent) per day
  • History of stroke or transient ischemic attack within 6 months prior to study enrollment
  • History of (non-infectious) pneumonitis /interstitial lung disease that required steroids, or has current pneumonitis/ interstitial lung disease
  • Presence of leptomeningeal disease
  • Any contraindication to MRI
  • Has received prior radiotherapy within 2 weeks of start of study treatment with dendritic cell (DC) vaccine and/or has received SRS > Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Seasonal influenza vaccines for injection are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed. Administration of killed vaccines is allowed.
  • Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug (DC vaccine)
  • Additional criteria apply

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