Allogeneic, Antigen-Presenting, GM-CSF-secreting, SV-BR-1-GM Whole Cell-Therapeutic Vaccine and Immunotherapy

Ki vehet részt

• Age ≥ 18 years
• Subject has a prior diagnosis of central nervous system (CNS) metastases per institutional standard of care and/or Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria on imaging
• Subject has disease progression of CNS metastases (brain and/or leptomeningeal metastases (LMD) ) with progression on ≥ 1 line of standard of care therapy
• Patients should have at least one metastasis approved by the research team that meets the following size requirements:; o Diagnosis and treatment response to measurable CNS and LMD will be per institutional and/or RANO-BM criteria modified to include the cut off point of 0.5 cm or higher; Patients with recurrent and or progressive symptomatic or asymptomatic brain lesions and >0.5 cm and twice the magnetic resonance imaging (MRI) slice thickness are allowed; Any recurrent or progressive brain lesions > 3 cm in size and or causing symptoms must be evaluated by the study team for SRC and or whole brain radiation therapy (WBRT) prior to study entry; Patients with recurrent brain lesions that are not treatable with local therapy or WBRT are eligible; 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); Patients should have recovered from the AEs of prior therapy to baseline or Grade ≤ 1; Patients with recurrent or progressive LMD are eligible
• Prior surgical resection of the brain metastases is allowed; patients must recover for at least four weeks prior to study enrollment
• Patients with extracranial disease are eligible as long as no signs of visceral crisis
• Prior immunotherapy is allowed
• No need for steroids for at least two weeks; Patients who recently started steroids should have completed tapering to be eligible; Patients who have been on chronic steroids are eligible as long as they are maintained on a dose of ≤ 10 mg of prednisone or equivalent
• Tumor not impinging on the middle cerebral artery/speech-motor strip
• Patients who undergo any other surgical procedures (other than SRS) must have recovered for at least 3-4 weeks before study entry
• Subject has a life expectancy of ≥ 12 weeks
• ECOG 0-2
• Preserved organ function; ANC ≥ 1,000/µl; Platelets ≥ 10,000 µl; Hemoglobin ≥ 8 gm/dL; Bilirubin ≤ 1.5 mg/dL; those with Gilbert syndrome may be included if their total bilirubin is ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN; Creatinine clearance ≥ 50 mL/min; AST, ALT ≤ 2.5 times institutional upper limit; ALP ≤ 2.5 × institutional upper limit, with the exception that ALP of < 5 x ULN is acceptable in patients with elevated ALP due to bone metastases (in the absence of liver metastases)
• Patients with lymphopenia are eligible at the discretion of the treating provider
• Female subjects must meet one of the following:; Postmenopausal for at least one year before enrollment, or surgically sterile (i.e., undergone bilateral oophorectomy); Premenopausal is defined as someone who has had menses at any time in the preceding 12 months. Premenopausal women who are eligible for this trial will require a GnRH analogue and treating physician, per institutional guidelines, may choose to monitor the ovarian function with laboratory tests (FSH/LH/Estradiol) to ensure a complete menopausal status with cessation of menses; Note: Pregnancy test should be administered per institutional guidelines
• Male patients must be willing to abstain from heterosexual activity and/or use a condom during treatment and three months after treatment discontinuation
• Willing to provide blood for biomarker assessments
• Optional CSF, when appropriate, for biomarker assessments (at the discretion of treating physician)
• Ability to understand a written informed consent document, and the willingness to sign it

Ki nem vehet részt

• History of last dose of antineoplastic therapy ≤ 7 days prior to the first dose of study drug. If sufficient wash-out time has not occurred (defined as 5 half-lives of the prior antineoplastic therapy), a longer wash-out may be needed, as suggested by the study team
• Patients with prior history of poorly controlled diabetes, lung disease, primary immunodeficiency syndromes
• Acute spinal cord compression, unless considered to have received definitive treatment for this and clinical evidence of stable disease for at least 28 days
• Active treatment with prednisone >10 mg or equivalent steroid (e.g., >1.5 mg dexamethasone) per day and/or other immunosuppressive therapies (e.g., interferon, azathioprine, mycophenolate)
• Active participation in other clinical trials evaluating an active investigational drug within the past four weeks
• Patients who received prior immune checkpoint inhibitors (CPIs) and have not recovered from Grade ≥ 2 AEs related to CPIs
• History of allergic reactions or intolerance to immunotherapy
• History of active or untreated infection, such as chronic untreated infections, HIV, Hepatitis B, Hepatitis C, or tuberculosis
• History of active inflammatory or autoimmune disease (granulomatosis, polyangiitis, Graves' disease, rheumatoid arthritis, polyphisitis, uveitis, etc.), except for the following; Vitiligo; alopecia; Hypothyroidism: stable on replacement therapy; Chronic skin disease that doesn't require steroid therapy; Active celiac disease or inflammatory bowel disease
• History of severe brain injury
• Patients with myelodysplastic syndrome (MDS), leukemia, or active blood disorders
• Severe cardiac disease as determined by the treating providers
• Presence of secondary malignancies (chronic lymphocytic leukemia [CLL], and other hematological or solid tumor malignancies), with the exception of in situ disease (ductal carcinoma in situ [DCIS], lobular carcinoma in situ [LCIS], cervical intraepithelial neoplasia [CIN], squamous cell and basal cell cancer, or remote history of successfully treated melanoma)
• Severe mental illness per physician's assessment
• Presence of severe neurological symptoms and unable to participate in the study due to acute decompensation
• Life expectancy <12 weeks
• Unresolved toxicities of NCI CTCAE Grade ≥ 2 such as neurotoxicity, cardiotoxicity, myelotoxicity, gastrointestinal, or others
• Women of childbearing potential who do not agree to precautions outlined in the inclusion criteria or having positive pregnancy tests
• Men who are sexually active and not willing to use effective contraceptives (e.g., condoms) during and 3 months after treatment
• Women who are pregnant or nursing