Table 1 Immunotherapy clinical trials for the treatment of brain metastases and leptomeningeal metastases
From: Immunotherapy: an emerging modality to checkmate brain metastasis
Immunotherapy | Clinical trial identifier | Cancer type | Status | Patient Enrollment Criteria | Therapy Design | Outcome measures/outcomes |
|---|---|---|---|---|---|---|
HER2.CAR T-cells | NCT03696030 | HER2 + BC and BrM and/or leptomeningeal metastases | Recruiting | -18 to 75 years old -Recurrent BrM after radiation therapy (RT) or chemotherapy or untreated BrM or leptomeningeal metastases. -Karnofsky performance status (KPS) ≥70 -Life expectancy of ≥8 weeks | Intraventricular administration for 5 min, 1 dose weekly for 3 weeks | -Safety of treatment -Determine recommended phase 2 dosing -Assess disease response rate based on the Response Assessment in Neuro-Oncology Criteria (RANO), which characterizes disease as stable disease (SD), partial response (PR), or complete response (CR) in the brain -Evaluate median progression-free (mPFS) and mOS -In patients who undergo tumor resection or biopsy, analyze the TME for HER2-CAR T-cells, immune cell subsets, cytokine levels, and HER2 antigen expression levels. |
Dendritic cell vaccines against HER2/HER3 with pembrolizumab | NCT04348747 | Metastatic TNBC or HER2 + BC | Recruiting | -Females ≥18 years old -Not pregnant or breastfeeding -Brain lesion must meet Response Assessment in Neuro-Oncology BrM (RANO-BM) criteria -Any BrM lesion between 0.5 cm to < 3.0 cm that is asymptomatic -Radiotherapy (RT) and/or Stereotactic radiosurgery (SRS) allowed ≥2 weeks prior to first dendritic cell (DC) vaccine dose, with at least ≥1 lesion left irradiated, to use as target lesion(s). | DC vaccine anti-HER2/HER3 administered intradermally (ID) on days 1, 22, and 43 | -Determine CNS response via RANO-BM -quantify BrM -Assess mPFS, mOS -Evaluate the safety of treatment |
Dendritic cell vaccines pulsed with mRNA encoded tumor antigens | NCT02808416 | Patients with BrM (all cancer types) | Completed | -18 to 65 years old -Undergo tumor resection or biopsy -Karnofsky scores ≥70 -No corticosteroid treatment at least one week before vaccine administration. | Biweekly mRNA-pulsed autologous dendritic cell vaccine. | -A total of 10 patients were treated with dendritic cell vaccines. -7 patients tested for anti-tumor associated antigens (TAAs), most of the TAAs induced either antigen-specific CD4 + or CD8 + T-cell responses or both -Patients treated with DC vaccines had improved OS compared to patients treated with standard therapy. |
Dendritic cell vaccine | NCT03638765 | BrM from BC or LC | Completed | -18 to 65 years old -Life expectancy > 12 weeks -≥1 CNS metastasis ≥10 mm per RANO-BM criteria -≥1 CNS metastasis available for reservoir placement | Injection of autologous dendritic cells intratumorally | -Evaluate the safety of treatment -Determine the feasibility of vaccine administration via Ommaya reservoir directly to tumor lesions -Ascertain tumor response, OS, neurocognitive functioning, and rate of intracranial recurrence. |
Anti-ESO (Cancer/Test Antigen) mTCR (T-cell receptor) -transduced autologous peripheral blood lymphocytes and chemotherapy for treating metastases of cancer expressing NY-ESO-1 | NCT02774291 | HLA-A2 + BrM | Completed | -18 to 65 years old -measurable cancer that expressed NY ESO-1 as assessed by RT-PCR or IHC or serum Ab reactive with ESO -Recurrent or untreated BrM after standard treatment -≤3 brain lesions -≥8 weeks from antibody therapy including anti-CTLA-4 therapy | administration of therapy via IV over 20–30 min on day 0. | -Determine the safety and tolerability of treatment -Evaluate in vivo survival rate of T-cell receptor-engineered cells -Evaluate the objective response rate via the Response Evaluation Criteria in Solid Tumors (RECIST) criteria |
Memory-like natural killer cells in combination with nivolumab and relatlimab | NCT05629546 | Advanced or metastatic melanoma (including stable BrM) | Active, not yet recruiting | -≥18 years old -Eastern Cooperative Oncology Group (ECOG) Performance Status < 3 | -IV infusion of memory-like natural killer cells on day 0 -relatlimab/nivolumab combination given at day 29, every 28 days for 11 cycles. | -adverse events -objective response rate -duration of response Progression-free survival -overall survival |
Durvalumab | NCT04356222 | Leptomeningeal metastases (LM) from NSCLC | Recruiting | -≥18 years old -pathological proof of primary NSCLC -the presence of malignant cells in CSF determined via MRI | IV infusion 1x bimonthly | -Neurological Progression Free Survival (NPFS) -overall survival -adverse events |
Avelumab | NCT03719768 | Leptomeningeal metastases (LM) | Active, not recruiting | -≥18 years old -life expectancy of > 8 weeks -negative pregnancy test -the presence of malignant cells in CSF or radiographic abnormalities suspecting of LM -At least 4 weeks following surgery of brain lesions | 1 h IV infusion given 1x weekly for 2 weeks | -the safety of the drug, measured via adverse events -activation and number of T cells -Leptomeningeal disease response rate measured via Response Assessment in Neuro-Oncology (RANO)-Brain Metastases (BrM) criteria -OS at 3 months |
Nivolumab | NCT03025256 | Leptomeningeal metastases (LM) | Active, not recruiting | -≥18 years old -must have radiographic or cytological evidence of LM -must be at least 7 days out from IT, if administered | -5 min intrathecal nivolumab on day 1 of every cycle -cycle 2, patients also receive IV nivolumab for 30 min on day 1 -18 cycles, each cycle 14 days long -after 18 cycles, each cycle is 28 days long | -adverse events -OS -immunological effects of nivolumab |