MDNA55: A locally administered IL4 guided toxin as a targeted treatment for recurrent glioblastoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2039-2039 ◽  
Author(s):  
Dina Randazzo ◽  
Achal Achrol ◽  
Manish K. Aghi ◽  
Martin Bexon ◽  
Steven Brem ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Negative Control ◽  
Recurrent Glioblastoma ◽  
Survival Outcomes ◽  
Tissue Banks ◽  
Open Label ◽  
Convection Enhanced Delivery ◽  
Sensitivity Testing ◽  
Specificity And Sensitivity ◽  
Recurrent Gbm

2039 Background: IL4 receptor (IL4R) is frequently and intensely expressed on a variety of human cancers and is associated with poor survival outcomes. Determining the role of the IL4R biomarker in glioblastoma (GBM) will be important for treatment with targeted therapies such as the IL4 fusion toxin MDNA55. Methods: A classification for IL4Rα expression in GBM tissues by H-Score was developed using a validated immunohistochemistry-based approach. MDNA55-05 is an open-label study of MDNA55 administered intratumorally via convection enhanced delivery in recurrent GBM. Levels of IL4Rα expression were assessed retrospectively in 24 subjects in the clinical trial and were correlated with GBM history, imaging responses and survival outcomes following treatment with MDNA55 to explore clinical validation. Results: Range, linearity, specificity and sensitivity testing using a rabbit polyclonal antibody to IL4Rα were performed using normal cortex (negative control) and a panel of normal human tissues and GBM cases from tissue banks. A total of 41 GBM samples were screened and grouped by reactivity thresholds: H-Scores ≥50 were observed in 95% of cases (39/41), H-Scores ≥200 were observed in 51% of cases (21/41), and H-Scores ≥250 were observed in 24% of cases (10/41). GBM tissues obtained at initial diagnosis from subjects enrolled in the trial show that moderate/high IL4R expression (H-Score > 75) was associated with shorter time to first relapse when compared to subjects with low IL4R expression (H-Score ≤ 75) (10.3 mos vs. 16.7 mos, respectively) after upfront standard-of-care treatment, consistent with published findings that IL4R expression is associated with more aggressive disease. Remarkable decreases in tumor size seen in some subjects following MDNA55 treatment were associated only with moderate/high IL4R expression and survival rate at 12 months in this group was also improved (OS12 = 55%) compared to subjects with low IL4R expression (OS12 = 30%). Conclusions: Treatment options for patients with recurrent GBM are very limited and positive outcomes remain rare. Targeting therapies such as MDNA55 by IL4R status may improve patient outcomes and help guide patient selection strategies for future clinical studies. Clinical trial information: NCT02858895.

A multicenter, 3-arm, open-label, phase IIa clinical trial to evaluate the safety and efficacy of tanibirumab (VEGFR2 mAb), in patients with recurrent glioblastoma (GBM).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13522-e13522 ◽  
Author(s):  
Lawrence Cher ◽  
Anna K. Nowak ◽  
George Iatropoulos ◽  
Weon Sup Lee ◽  
Seon Young Lee ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Signal Transduction Pathway ◽  
Study Drug ◽  
Current Data ◽  
Recurrent Glioblastoma ◽  
Open Label ◽  
Eligibility Criteria ◽  
Impaired Wound Healing ◽  
Safety And Efficacy ◽  
Recurrent Gbm

e13522 Background: Treatment of recurrent GBM remains a challenge. The VEGF signal transduction pathway is upregulated in GBM. We evaluated Tanibirumab, a mAb to VEGFR2, in an open-label, dose-escalation, 3-arm, Phase 2a clinical trial. Primary and secondary endpoints were determining safety and efficacy (6-month PFS, ORR, DCR and OS). Methods: Eligibility criteria included age ≥19 yrs at 1st or 2nd recurrence of GBM, measurable disease, KPS≥80, and no prior bevacizumab. Patients were enrolled in 3 arms: Arm 1 (8mg/kg d1,8,15/q28 days); Arm 2 (12mg/kg d1,8,15/q28 days) and Arm 3 (12mg/kg weekly). Response evaluation with MRI (RANO criteria) including DCE, was performed every 2 cycles. Results: 12 patients were enrolled over 10 months from 2 sites: 3 patients each in Arms 1 & 2; 6 in Arm 3. The median age was 50 years and 8 were male. 6 patients had second recurrence. At 1st infusion, 8 out of 12 were on baseline corticosteroids. 10 patients have progressed. No dose limiting toxicities (DLT) were observed. Cutaneous hemangiomas (CH) were frequent (83% of patients) and all G2 or less. No drug-related G3 or 4 AEs were observed. All SAEs were unrelated to the study drug apart from G2 bleeding haemangioma and G2 cerebral haemorrhage. Expected AEs with anti-angiogenic drugs (hypertension; impaired wound healing) were not observed. Among 12 patients allocated to Arm 1, 2 and 3, no objective radiological responses were observed. 3 patients demonstrated stable disease (SD); 2 patients had SD beyond 4 cycles and are still receiving treatment at weeks 45 (Arm 1) & 20 (3). This was correlated with the highest expression of VEGFR2 using immunohistochemistry on archival tumour and blood vessels. Only 2 patients needed to initiate or increase corticosteroids for control of tumor edema while on treatment. Current data are immature to determine time to event efficacy endpoints (PFS,OS). Conclusions: Tanibirumab can be safely administered to patients with recurrent GBM, with CH being common. SD was seen in 2 patients up to 10+ months, with some indication that VEGFR2 expression may be a response biomarker. Clinical trial information: NCT03033524.

scholarly journals ACTR-26. SAFETY AND EFFICACY OF BEVACIZUMAB PLUS TTFIELDS IN PATIENTS WITH RECURRENT GLIOBLASTOMA (GBM): DATA FROM A PHASE II CLINICAL TRIAL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi18-vi18 ◽  
Author(s):  
Jaleh Fallah ◽  
Rekha Chaudhary ◽  
Lisa Rogers ◽  
Wei (Auston) Wei ◽  
Cathy Brewer ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Disease Progression ◽  
Muscle Weakness ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Open Label ◽  
Safety And Efficacy ◽  
Phase 2 Clinical Trial ◽  
Recurrent Gbm

Abstract BACKGROUND Studies of bevacizumab monotherapy and TTFields monotherapy have shown activity but limited clinical benefit in patients with recurrent GBM. In an open label, single-arm, phase 2 clinical trial, the safety and efficacy of the combination of bevacizumab and TTFields was studied in patients with recurrent GBM. METHOD Bevacizumab-naïve patients with histologically confirmed GBM or other grade IV glioma, with recurrent disease after radiotherapy and temozolomide chemotherapy, were eligible. Bevacizumab dose was 10mg/kg intravenously every 2 weeks and TTFields was worn at least 18 hours daily. The primary endpoint was safety, progression-free survival at 6 months (PFS6) and overall survival at 12 months (OS12). Treatment was continued until disease progression or unacceptable toxicity. Survival outcomes were assessed using the Kaplan-Meier method. Treatment-related adverse events were reported according to CTCAE, v4.0 criteria. RESULTS 25 patients were enrolled and 23 were eligible for data analysis: 18 (78%) men and 5 (22%) women, median age 60 years (range 17–78). 21 patients were Caucasian, 1 was African American and 1 of unknown race. Median follow-up was 6.0 months (range 2.4–22). Seven patients (30 %) had disease progression. Median PFS was 9.9 (95% CI: 6.7-NA) months. PFS rate at 6 months (PFS6) was 71% (95% CI: 0.54–0.94). Median overall survival was 9.9 (95%CI 7.3-NA) months. OS rate at 12 months (OS12) was 42% (95%CI 0.24–0.74). 7 patients (30%) had grade 3 toxicity (cough, dysphagia, muscle weakness, hyperglycemia, hypertension, psychosis, seizure, lymphopenia, transaminitis). 1 patient developed grade 4 muscle weakness in the lower extremities. CONCLUSION Treatment with the combination of bevacizumab and TTFields in patients with recurrent GBM is safe and feasible and has shown clinical efficacy.

scholarly journals SURG-13. LASER INTERSTITIAL THERMAL THERAPY FOR RECURRENT GLIOBLASTOMA: A REVIEW OF SURVIVAL OUTCOMES COMPARED TO A MATCHED SURGICAL COHORT

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii206-ii206
Author(s):  
Hassan Fadel ◽  
Sameah Haider ◽  
Jacob Pawloski ◽  
Hesham Zakaria ◽  
Farhan Chaudhry ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Subgroup Analysis ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Thermal Therapy ◽  
Survival Outcomes ◽  
Repeat Surgery ◽  
Laser Interstitial Thermal Therapy ◽  
Recurrent Gbm

Abstract INTRODUCTION Glioblastoma (GBM) is uniformly associated with a poor prognosis and inevitable recurrence. Management of recurrent GBM remains unclear, with repeat surgery often employed with varying degrees of success. We evaluated the efficacy of Laser Interstitial Thermal Therapy (LITT) for recurrent GBM when compared to a carefully matched cohort of patients treated with repeat surgical resection. METHODS A retrospective single-institution database was used to identify patients who underwent LITT or surgical resection of recurrent GBM between 2014-2019. LITT patients were matched with surgical resection patients according to baseline demographics, comorbidities, tumor location, and eloquence. Subgroup analysis matching similar patients for tumor volume was also completed. Overall survival (OS) and progression-free survival (PFS) were the primary endpoints. RESULTS A LITT cohort of 20 patients was matched to 50 similar patients who underwent repeat surgical resection. Baseline characteristics were similar between both cohorts apart from tumor volume, which was larger in the surgical cohort (17.5 cc vs. 4.7 cc, p< 0.01). On long-term follow-up, there was no difference in OS (HR, 0.72; 95%CI, 0.36-1.45) or PFS (HR, 0.67; 95%CI, 0.29-1.53) between the LITT and surgical cohorts when controlling for tumor volume. Subgroup analysis of 23 LITT patients matched according to tumor volume with 23 surgical patients with similar clinical characteristics also found no difference in OS (HR, 0.66; 95%CI, 0.33-1.30) or PFS (HR, 0.58; 95%CI, 0.90-1.05) between the cohorts. LITT patients had shorter length of stays (1 vs. 4 days, p< 0.001) and a higher rate of home discharge (84% vs. 67%, p=0.172) compared to the surgical cohort. CONCLUSION After matching for demographic, clinical, and tumor characteristics, there was no difference in outcomes between patients undergoing LITT compared to surgical resection for recurrent GBM. LITT patients had similar survival outcomes yet shorter hospital stays and more favorable dispositions, potentially mitigating post-treatment complications.

scholarly journals CTNI-14. A 3-ARM, PHASE IIA TRIAL OF SAFETY & EFFICACY OF OLINVACIMAB, A MONOCLONAL ANTIBODY TO VEGFR2 IN PATIENTS WITH RECURRENT GLIOBLASTOMA MULTIFORME WITH IMAGING AND PK/PD ASSESSMENTS: FINAL REPORT

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii44-ii45
Author(s):  
Lawrence Cher ◽  
Anna Nowak ◽  
George Iatropoulos ◽  
Samantha Bowyer ◽  
Hui Gan ◽  
...  
Keyword(s):  
Recurrent Glioblastoma ◽  
Final Report ◽  
Recurrent Glioblastoma Multiforme ◽  
Open Label ◽  
Impaired Wound Healing ◽  
Significant Difference ◽  
Angiogenic Effect ◽  
Vegf Pathway ◽  
Recurrent Gbm

Abstract The VEGF pathway remains an important target in GBM given its vascularity and autocrine VEGF signalling. Olinvacimab (TTAC-0001) is a fully humanised VEGFR2 Mab that binds and inhibits the receptor. This report assesses the safety, dosing schedules and efficacy of Olinvacimab in recurrent GBM. We conducted a two-site, 3 arm, open-label study of Olinvacimab in recurrent GBM. Eligible patients were ≥18 years with RANO-measurable lesion, KPS ≥ 80, and had completed chemoradiotherapy without prior bevacizumab therapy. We assessed three arms, 8 mg/kg and 12mg/kg weekly for 3 of every 4 weeks, and 12 mg/kg weekly. Three patients were treated in arms 1 and 2 and 6 in arm 3. Safety assessments were performed prior to dose escalation. The main toxicity was development of grade 1 (67%) and 2 (8%%) cutaneous haemangiomas. Common toxicities seen with other VEGF directed therapies, including hypertension, impaired wound healing, and proteinuria were not seen in this cohort. Efficacy was assessed by MRI using RANO criteria. 6 month PFS was 17%, with disease control in 25%, with steroid dose reduction. The longest response was 15 months. On DCE MRI, there was no significant difference in perfusion parameters between baseline and 1st follow-up MRI comparing those with SD and PD. However, 6 of 12 patients showed decreased Ktrans > 20 % of baseline, consistent with an anti-angiogenic effect of Olinvacimab. Pharmacokinetics showed a decreased clearance rate and increased half-life of Olinvacimab compared to the prior Phase I study. Pharmacodynamic studies showed significantly higher levels of angiogenic markers, particularly VEGF-A in those treated at 12mg/kg vs arm 1. VEGF-A, C and D levels were elevated in patients with SD compared to those with PD. Conclusion: Olinvacimab was well tolerated with a different toxicity profile to other VEGFR directed therapies. There were promising responses in 25% of patients.

Cyto-KIK: A phase II trial of cytoreductive surgery in kidney cancer plus immunotherapy (nivolumab) and targeted kinase inhibition (cabozantinib).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4598-TPS4598
Author(s):  
Karie Runcie ◽  
Eric A. Singer ◽  
Moshe Chaim Ornstein ◽  
Christopher B. Anderson ◽  
Matthew Dallos ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Cytoreductive Nephrectomy ◽  
Open Label ◽  
Orthotopic Mouse Model

TPS4598 Background: Despite recent therapeutic advancements in metastatic renal cell carcinoma (mRCC), only 5-10% of patients will achieve a complete response (CR) to therapy. Cytoreductive nephrectomy removes a large portion of the tumor which may be a source of immunosuppression driven by tumor cell-intrinsic factors in the tumor microenvironment. A pre-clinical orthotopic mouse model of aggressive metastatic triple negative breast cancer showed that neoadjuvant anti-PD-1 checkpoint inhibition generated enhanced and sustained antitumor immune responses with improved survival compared to adjuvant therapy (Liu J et al. Cancer Discov. 2016:1382). Clinical validation of improved outcomes with neoadjuvant compared to adjuvant immune checkpoint inhibitors has been demonstrated in trials for patients with non-small cell lung cancer, advanced melanoma, and recurrent glioblastoma (Forde, P.M., et al. N Engl J Med. 2018:1976; Amaria, R.N., et al Nat Med. 2018:1649; Cloughesy T.F., et al. Nat Med 2019:477). Recent data from a phase III trial in subjects with untreated mRCC, demonstrated the superiority of combination cabozantinib and nivolumab over sunitinib and established a new standard of care for mRCC (Choueiri T.K., et al. Annals of Onc, 2020;31 (suppl; abstr 6960). We hypothesize that if tumor specific immune responses to immunotherapy are greatest prior to nephrectomy, then treatment with nivolumab (nivo) and cabozantinib (cabo) prior to cytoreductive nephrectomy will lead to maximal peripheral and intra-tumoral specific immune responses and higher rates of CR during the course of treatment. Methods: This is an open label phase II, multicenter clinical trial of combination nivo and cabo prior to cytoreductive nephrectomy in patients with mRCC (NCT04322955). 48 treatment- naïve subjects with radiological or histological diagnosis of mRCC will be enrolled with the primary endpoint of CR rate according to RECIST version 1.1. Subjects will receive cabo (40mg) daily and nivo (480mg) every 4 weeks for 12 weeks prior to nephrectomy and a 3+3 design will be used to evaluate the safety of the interval (21 or 14 days) between the discontinuation of cabo and nephrectomy. Post-operatively, subjects will resume treatment with cabo and nivo until evidence of disease progression. Secondary endpoints include median size reduction of the primary tumor, response rate, PFS, OS, and surgical outcomes using the Clavien-Dindo classification system. Tissue based assays will quantify treatment related changes in the renal tumor microenvironment through polychromatic immunofluorescence, single cell RNA sequencing of the biopsy and nephrectomy specimen, and multiplex assessment of circulating serum cytokines. Dynamic contrast-enhanced MRI will be performed in a subset of subjects to assess radiologic correlates of response. The study is currently open to enrollment. Clinical trial information: NCT04322955.

Phase II trial of cytoreductive surgery in kidney cancer plus immunotherapy (nivolumab) and targeted kinase inhibition (cabozantinib) (Cyto-KIK).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS371-TPS371
Author(s):  
Karie Runcie ◽  
Eric A. Singer ◽  
Moshe Chaim Ornstein ◽  
Christopher B. Anderson ◽  
Matthew Dallos ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Cytoreductive Nephrectomy ◽  
Open Label ◽  
Orthotopic Mouse Model

TPS371 Background: Despite recent therapeutic advancements in metastatic renal cell carcinoma (mRCC), only 5-10% of patients will achieve a complete response (CR) to therapy. Cytoreductive nephrectomy removes a large portion of the tumor which may be a source of immunosuppression driven by tumor cell-intrinsic factors in the tumor microenvironment. A pre-clinical orthotopic mouse model of aggressive metastatic triple negative breast cancer showed that neoadjuvant anti-PD-1 checkpoint inhibition generated enhanced and sustained antitumor immune responses with improved survival compared to adjuvant therapy (Liu J et al. Cancer Discov. 2016:1382). Clinical validation of improved outcomes with neoadjuvant compared to adjuvant immune checkpoint inhibitors has been demonstrated in trials for patients with non-small cell lung cancer, advanced melanoma, and recurrent glioblastoma (Forde, P.M., et al. N Engl J Med. 2018:1976; Amaria, R.N., et al Nat Med. 2018:1649; Cloughesy T.F., et al. Nat Med 2019:477). Recent data from a phase III trial in subjects with untreated mRCC, demonstrated the superiority of combination cabozantinib and nivolumab over sunitinib and established a new standard of care for mRCC (Choueiri T.K., et al. Annals of Onc, 2020;31 (suppl; abstr 6960). We hypothesize that if tumor specific immune responses to immunotherapy are greatest prior to nephrectomy, then treatment with nivolumab (nivo) and cabozantinib (cabo) prior to cytoreductive nephrectomy will lead to maximal peripheral and intra-tumoral specific immune responses and higher rates of CR during the course of treatment. Methods: This is an open label phase II, multicenter clinical trial of combination nivo and cabo prior to cytoreductive nephrectomy in patients with mRCC (NCT04322955). 48 treatment- naïve subjects with radiological or histological diagnosis of mRCC will be enrolled with the primary endpoint of CR rate according to RECIST version 1.1. Subjects will receive cabo (40mg) daily and nivo (480mg) every 4 weeks for 12 weeks prior to nephrectomy and a 3+3 design will be used to evaluate the safety of the interval (21 or 14 days) between the discontinuation of cabo and nephrectomy. Post-operatively, subjects will resume treatment with cabo and nivo until evidence of disease progression. Secondary endpoints include median size reduction of the primary tumor, response rate, PFS, OS, and surgical outcomes using the Clavien-Dindo classification system. Tissue based assays will quantify treatment related changes in the renal tumor microenvironment through polychromatic immunofluorescence, single cell RNA sequencing of the biopsy and nephrectomy specimen, and multiplex assessment of circulating serum cytokines. Dynamic contrast-enhanced MRI will be performed in a subset of subjects to assess radiologic correlates of response. The study is currently open to enrollment. Clinical trial information: AAAS6927 .

CTIM-28. MDNA55, AN INTERLEUKIN-4 RECEPTOR TARGETED IMMUNOTHERAPY, FOR RECURRENT GBM DELIVERED BY CONVECTION ENHANCED DELIVERY (CED)

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi56-vi57
Author(s):  
John Sampson ◽  
Achal Singh Achrol ◽  
Manish K Aghi ◽  
Krystof Bankiewiecz ◽  
Martin Bexon ◽  
...  
Keyword(s):  
De Novo ◽  
Symptom Control ◽  
Recurrent Glioblastoma ◽  
Interleukin 4 ◽  
External Control ◽  
High Dose ◽  
Open Label ◽  
Convection Enhanced Delivery ◽  
High Concentrations ◽  
Dose Volumes

Abstract BACKGROUND MDNA55 is an IL4R-targeted toxin in development for treatment of recurrent glioblastoma (rGBM). MDNA55 binds to IL4R expressed by tumor cells and non-malignant cells of the tumor microenvironment. METHOD MDNA55-05 was an open-label, single-arm study of MDNA55 delivered by CED as a single treatment in patients with 1st or 2nd recurrence following de novo GBM, IDH wild type status and not indicated for resection at relapse. Dose volumes (up to 60mL) and concentration of MDNA55 (1.5 to 9.0 μg/mL) were studied. RESULTS MDNA55 showed an acceptable safety profile at all doses tested. Median OS (mOS) amongst all subjects was 11.9 months, OS-24 was 20%, and PFS-12 was 27%. Among subjects expressing high levels of IL4R (irrespective of MDNA55 dose) and low levels of IL4R expression administered high dose (≥ 180μg) of MDNA55 (IL4Rhi + IL4Rlo/hd), mOS further improved to 14.0 months with OS-24 of 20%. Unmethylated MGMT promoter status did not affect MDNA55 treatment outcomes. In the IL4Rhi + IL4Rlo/hd population (N=17), mOS was 14.9 months with OS-24 of 22%. Following treatment with high concentrations of MDNA55 (6.0 or 9.0 μg/mL), transient (median of 3 cycles) low dose Avastin (5mg/kg q2w or 7.5mg/kg q3w) was used for symptom control and steroid sparring. Among these subjects, mOS amongst all comers (N=9) and the IL4Rhi + IL4Rlo/hd group (N=8) increased to 21.8 and 18.6 months with OS-24 of 44% and 38%, respectively. CONCLUSIONS MDNA55 shows potential to benefit all rGBM patients treated at high dose irrespective of IL4R expression. In the 1:1 randomized Phase 3 trial, the study will enrol two-thirds of subjects in the SOC arm from a matched external control arm. Unlike conventional RCTs, the hybrid design sets a new precedent for GBM trials, allowing robust OS analysis while significantly reducing the number of subjects randomized to SOC arm.

scholarly journals ACTR-68. FEASIBILITY STUDY OF THE EMULATE THERAPEUTICS™ VOYAGER SYSTEM IN PATIENTS WITH RECURRENT GLIOBLASTOMA (GBM)

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi29-vi29
Author(s):  
Garni Barkhoudarian ◽  
Michael Badruddoja ◽  
Nicholas Blondin ◽  
Ricky Chen ◽  
Sajeel Chowdhary ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Skin Irritation ◽  
Recurrent Glioblastoma ◽  
Secondary Outcome ◽  
Open Label ◽  
Serious Adverse Events ◽  
Radio Frequency Energy ◽  
Long Term Treatment ◽  
Recurrent Gbm

Abstract BACKGROUND The EMulate Therapeutics Voyager system is an investigational non-sterile, non-invasive, non-thermal, non-ionizing, portable, home-use medical device that uses a specific, localized ultra-low radio frequency energy (ulRFE®) cognate for the treatment of brain cancer. METHODS This ongoing, open-label, multi-center study (NAT-101) is being conducted in the US and Australia in patients with recurrent GBM. There are 3 treatment groups: 32 patients treated with Voyager alone, 43 patients treated with Voyager + Investigator’s choice of anti-cancer therapy, and 21 patients treated with Voyager+lomustine+/-bevacizumab. The objective of the study is to assess if the Voyager is a safe and feasible treatment for recurrent GBM. The primary outcome measure is safety, assessed by the incidence and evaluation of adverse events (AEs) associated with the Voyager. The secondary outcome measures are progression-free survival and overall survival. RESULTS Enrollment is closed, and long-term treatment and follow-up is ongoing. 96 patients were enrolled and treated. 82 patients reported at least one AE, and 18 AEs were assessed as device-related (mild-moderate; 12 headache, 2 vomiting, 1 nausea, 1 confusion, 1 insomnia, and 1 skin irritation). 31 patients reported at least one serious AE, and none were assessed as device-related. 33% of patients treated with Voyager alone and 36% of patients treated with Voyager + chemotherapy were progression-free after 6 months. 58% of patients treated with Voyager alone and 60% of patients treated with Voyager + chemotherapy remained alive after 6 months; median overall survival is 7 months (95% CI=4.4±14.3) in patients treated with Voyager alone and 10 months (95% CI=6.7±11.5) in patients treated with Voyager + chemotherapy. CONCLUSIONS The Voyager system appears to be safe and feasible for the treatment of recurrent GBM. Given that therapy is delivered non-invasively and no device-related serious adverse events were reported, further prospective study of the investigational device is planned.

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