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Background Systemic therapies for refractory meningiomas are limited with no FDA-approved therapeutics. Vascular endothelial growth factor (VEGF) is a signaling protein associated with neovascularization, peritumoral edema, and meningioma tumorigenesis. Methods This phase II study investigates the efficacy of bevacizumab (BEV), a VEGF binding monoclonal antibody, in patients with progressive Grade I (G1M), Grade II (G2M), Grade III (G3M) meningioma, and other non-parenchymal tumors including vestibular schwannoma (n = 4) and hemangiopericytoma (n = 4) with the primary endpoint of progression-free survival rate at 6-months (PFS-6). Non-meningiomas were included with the respective meningioma grade in the analysis. Secondary endpoints include median overall survival (mOS) and response rate. Results Fifty Patients (26 women; median age 54 years; range 23–81), 42 with progressive meningioma were treated: 10 G1M, 20 G2M, and 12 G3M. Prior treatments include surgical resection (41 patients), radiosurgery (24 patients), external beam radiotherapy (28 patients), and chemotherapy (14 patients). Median infusions administered were 16 (range, 2–68). Response was graded using the Macdonald’s criteria. PFS-6, median PFS, and mOS were 87%, 22 months, 35 months for G1M; 77%, 23 months, 41 months for G2M; and 46%, 8 months, 12 months for G3M. Best radiographic responses include stable disease (G1M: 100%; G2M: 85%; G3M: 82%); partial response (G1M: 0%; G2M: 5%; G3M: 0%) and progressive disease (G1M: 0%; G2M: 10%; G3M:18%). The most common toxicities were hypertension (n = 19, 42.2%), proteinuria (n = 16, 35.6%), and fatigue (n = 14, 31.1%). Conclusion This study showed BEV is well tolerated and appears to be a promising systemic treatment option for patients with recurrent and refractory meningiomas.

3014 Background: The oncogenic transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) promotes tumor survival and proliferation and inhibits differentiation. ST101 is a peptide antagonist of C/EBPβ, with anti-tumor activity in prostate cancer (PC), glioblastoma (GBM), breast cancer (BC), melanoma, and other pre-clinical models. Methods: This phase 1 study enrolled patients (pts) with refractory solid tumors with varying histologies. The primary objective was to evaluate safety/tolerability of ST101 and to determine the recommended phase 2 dose (RP2D). Secondary and exploratory objectives included pharmacokinetics (PK), preliminary efficacy (RECIST 1.1), and pharmacodynamic (PD) evaluation. The study used a 3+3 dose-escalation design, with once-weekly IV infusion dosing of ST101 at 0.5, 1, 2, 4, 6, 9 mg/kg or a flat dose of 500 mg. Results: Enrollment in phase 1 was completed in November 2021 with a total of 25 pts with multi-metastatic disease that were refractory to standard therapy. As of February 15, 2022, five pts remain on study with a median treatment duration of 27 weeks’ (16-77). There were no DLTs, dose modifications, or serious adverse events (SAEs) related to ST101. The only AEs of note were G1-2 histaminergic infusion-related reactions (IRRs), largely pruritis and urticaria, managed with antihistamines, montelukast, and interruption/slowing of infusion. IRRs affected 93% of pts on the first dose at ≥4mg/kg and led to prolongation of infusion time. Intensity and frequency of IRRs decrease with repeat dosing. No other AEs were consistently reported. There was no evidence of accumulation upon continued exposure of ST101 and no anti-drug antibodies. Tumor immunohistochemistry showed dose-proportionate staining for ST101 and decreased tumor proliferation in several pts represented by decreased Ki67 expression. Population PK analysis supported flat dosing in phase 2. Five pts continue on treatment with one confirmed partial response in a patient with cutaneous melanoma lasting >42 weeks and four pts with ongoing stable disease. Conclusions: ST101 demonstrated safety at all doses explored and evidence of efficacy across dose levels, particularly higher doses and in pts with melanoma. PK and PD support a dose relationship for efficacy and selection of 500 mg as the RP2D. Pts are now enrolling in phase 2 cohorts to assess response in cutaneous melanoma, GBM, castrate-resistant PC, and HR+ BC. Clinical trial information: NCT04478279. [Table: see text]

2014 Background: Cytomegalovirus (CMV) antigens have been reported in over 90% of GBMs. CD4+ and CD8+ T cells are most frequently directed against the gB and pp65 antigens, respectively, which are immunogenic targets in a CMV-based GBM immunotherapeutic. Methods: A total of 20 first-recurrent GBM patients were enrolled, with Karnofsky Performance Status of at least 70, across 2 arms of the Phase IIa extension phase to receive VBI-1901 (a gB/pp65 enveloped virus-like particle [eVLP]) adjuvanted with either GM-CSF (given intradermally) or AS01B (given intramuscularly) (NCT03382977). Patients were vaccinated with VBI-1901 every 4 weeks, with serologic immune-monitoring 2 weeks after each vaccination and surveillance brain MRI scans every 6 weeks. Results: 10 patients (6 women, 4 men) with a median age of 58 (33-67 yrs) were enrolled into the GM-CSF arm and 10 patients (3 women, 7 men) with a median age of 65 (40-67) enrolled into the AS01B arm. The 12-month OS rates for the GM-CSF and AS01B arms were 60% and 70%, respectively; the 18-month OS rate for the GM-CSF arm was 30%, and for the AS01B arm is expected to be 30%-40% (data has not yet matured). Two durable partial responses (locally determined by RANO) have been observed in the GM-CSF arm, with one patient progression-free and on protocol after 2 years with a tumor size reduction of 93% relative to start of treatment. Immunological analyses demonstrate that prolonged, monthly dosing with VBI-1901 does not lead to immunological tolerance. Dynamic boosting and loss in the peripheral blood of CMV-specific CD4 Tem cells after treatment with VBI-1901 formulated with GM-CSF may correlate with tumor responses. Conclusions: The U.S. FDA granted Fast Track Designation to VBI-1901 adjuvanted with GM-CSF in first-recurrent GBM patients, and an expansion of the ongoing trial with this formulation in this patient population, with the addition of randomization with a contemporaneous control arm, is anticipated to begin in H1 2022. Acknowledgement: GlaxoSmithKline Biologicals SA provided the AS01B adjuvant used in this study. Clinical trial information: NCT03382977.

TPS2084 Background: Glioblastoma Multiforme (GBM), is the most common and aggressive brain tumor. Tumor Treatment Fields (TTFields) is a noninvasive, regional antimitotic treatment modality approved for the treatment of recurrent and newly diagnosed GBM by the US Food and Drug Administration. TTFields delivers low intensity (1-3 V/cm), intermediate frequency (100-300 kHz), alternating electric fields to the tumor through noninvasive transducer arrays placed on the skin, around the region of the body containing the tumor. During mitosis, TTFields disrupt the formation of the mitotic spindle during metaphase resulting in apoptosis. Dermatologic adverse events (AEs) to TTFields include dermatitis and infections and were reported in 54% of patients in a phase III trial. Topical triamcinolone and clindamycin have demonstrated anecdotal benefit because of their anti-inflammatory and antimicrobial activity. Pre-clinical studies have shown no negative effect on impedance when applied onto skin under the arrays. The effect of topical triamcinolone and clindamycin for the prevention of skin AEs to TTFields has not been studied prospectively. Methods: We are conducting a phase II multicenter clinical trial in patients receiving standard-of-care TTFields therapy for GBM to determine the efficacy of a prophylactic intervention: topical clindamycin 1% solution and triamcinolone 0.1% lotion in preventing grade ≥2 epicutaneous device-related events. Eligible patients must be ≥18 years of age, newly diagnosed with GBM and initiating TTFields within 7 days of study enrollment. The primary objective is to determine the effect of topical clindamycin 1% and triamcinolone 0.1% on the prevention of grade ≥2 device-related skin AEs. Secondary objectives include investigating the effect of study agents on skin-related quality of life (using the PRO-CTCAE modules for rash, ulcer, and pruritus), evaluating the efficacy of study agents applied to the scalp at every array change by standardized photography evaluated by a blinded investigator, measuring the duration of skin toxicities and usage of the TTFields device, measuring the duration of treatment interruptions and time to first grade ≥ 2 skin events, determining the bacterial flora of scalp infections, and determining the effect of study agents on TTFields’ impedance. Patients will be on study for 90 days. An end-of-study assessment will occur on day 90, and a post-treatment visit will occur on day 120. The first patient was enrolled on October 21, 2020 and hitherto, 8 patients have been consented. Participating sites include Memorial Sloan Kettering Cancer Center, Columbia University Medical Center, Tufts University Medical Center, Northwestern University, Washington University, University of Cincinnati, and John Theurer Cancer Center - Hackensack Meridian Health. Clinical trial information: NCT04469075.