Status:
NOT_YET_RECRUITING
Allogeneic, Antigen-Presenting, GM-CSF-secreting, SV-BR-1-GM Whole Cell-Therapeutic Vaccine and Immunotherapy: A Phase I Pilot Safety and Feasibility Study for Solid Tumor Patients With CNS Metastases
Lead Sponsor:
Medical College of Wisconsin
Conditions:
Brain Metastases
Leptomeningeal Metastasis
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
This is a prospective, single-center, phase 1 basket trial that will evaluate the safety and feasibility of administering SV-BR-1-GM in combination with pembrolizumab to solid tumor oncology patients ...
Detailed Description
This prospective, single-site, open-label, single-arm, phase 1 basket trial is designed to evaluate whether a SV-BR-1-GM vaccine and pembrolizumab combination therapy is safe and can be feasibly admin...
Eligibility Criteria
Inclusion
- 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.
- i. 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.
Exclusion
- 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
- Presence of severe neurological symptoms and unable to participate in the study due to acute decompensation.
- History of severe brain injury.
- 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 myelodysplastic syndrome (MDS), leukemia, or active blood disorders.
- Patients with prior history of poorly controlled diabetes, lung disease, primary immunodeficiency syndromes.
- Severe cardiac disease as determined by the treating providers.
- Life expectancy \<12 weeks.
- 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).
- 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).
- Active participation in other clinical trials evaluating an active investigational drug within the past four weeks.
- Unresolved toxicities of NCI CTCAE Grade ≥ 2 such as neurotoxicity, cardiotoxicity, myelotoxicity, gastrointestinal, or others.
- Patients who received prior immune checkpoint inhibitors (CPIs) and have not recovered from Grade ≥ 2 AEs related to CPIs.
- 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.
- Severe mental illness per physician's assessment.
Key Trial Info
Start Date :
March 1 2026
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
April 1 2029
Estimated Enrollment :
20 Patients enrolled
Trial Details
Trial ID
NCT07199413
Start Date
March 1 2026
End Date
April 1 2029
Last Update
September 30 2025
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