Survival of subjects with recurrent glioblastoma receiving intratumoral administration of controlled IL-12 with limited exposure to dexamethasone.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2564-2564
Author(s):  
Rimas Vincas Lukas ◽  
Sylvia Christine Kurz ◽  
John Yu ◽  
Joseph C. Landolfi ◽  
Ganesh Rao ◽  
...  
Keyword(s):  
Phase 1 ◽  
Recurrent Glioblastoma ◽  
Interleukin 12 ◽  
Main Study ◽  
Intratumoral Administration ◽  
Immune System Activation ◽  
Multifocal Disease ◽  
The Impact ◽  
Subject Characteristics

2564 Background: Interleukin-12 (IL-12) results in anti-tumor responses in preclinical models but requires tightly controlled production to achieve safety and elicit immune system activation to realize efficacy. A phase 1 “main study” (NCT02026271) enrolled subjects with Grade III or IV gliomas who at the time of resection received intratumoral administration of a replication-deficient adenovirus expressing IL-12 under control of a transcriptional switch (Ad-RTS-hIL-12, Ad) regulated by veledimex (V), referred to as “Controlled IL-12”. It was anticipated that dexamethasone (dex), a lymphocytotoxic corticosteroid used to control edema, might diminish response to immunotherapies. We report updated findings from a substudy of subjects who were dex-free during the 4 weeks prior to Ad administration. Methods: Multicenter, phase 1 substudy (NCT03679754) that assesses safety and tolerability of Controlled IL-12 by local injection (Day 0, time of resection) of Ad (2 x 1011 viral particles) + V (20 mg PO QD x15 doses, Days 0-14) in subjects that were bevacizumab naïve and not receiving dex 4 weeks prior to Ad. Results: 36 subjects were treated. Of the 36, a majority received low-dose corticosteroids (≤ 20 mg dex total during V) as compared with the main study (75% vs 40%). More subjects in the substudy as compared with the main study had multifocal vs. unifocal disease (39% vs 7%). The safety profile was similar for both. Adverse reactions were mild to moderate and were manageable and reversable upon withholding V. Activation of the switch in both the main study and substudy (V 20 mg; n = 51) resulted in increased mean peak values (Day 0-28) of serum IL-12 (25.8 vs. 20.4 pg/mL) and IFN-g (57.0 vs. 39.5 pg/mL). Initial median overall survival (mOS) (unifocal, ≤ 20 mg dex cumulative, n = 20) was 16.2 (8.9, 18.5) mons (mean follow-up 12.3 mons) (Neuro Oncol 2019; 21 [suppl_6]:vi5). mOS including the impact of dex and key subject characteristics from the two studies (n = 51) will be updated and tumor response data will be provided. Conclusions: Monotherapy with Controlled IL-12 resulted in sustained increase in serum recombinant IL-12 and downstream endogenous IFN-g. There is evidence of immune-mediated anti-tumor effects which is associated with increased mOS as compared with historical controls. Follow up will investigate the adverse impact of dex, as well as the effect of additional subject characteristics ( e.g., unifocal vs. multifocal disease) on mOS. Clinical trial information: NCT03679754 .

Evaluation of controlled IL-12 as monotherapy in subjects with recurrent GBM.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2053-2053
Author(s):  
Rimas Vincas Lukas ◽  
E. Antonio Chiocca ◽  
Sylvia Christine Kurz ◽  
John Yu ◽  
Joseph C. Landolfi ◽  
...  
Keyword(s):  
Immune System ◽  
Transcriptional Control ◽  
Low Dose ◽  
Cytotoxic T Cells ◽  
Phase 1 ◽  
Intratumoral Injection ◽  
Recurrent Glioblastoma ◽  
Interleukin 12 ◽  
Main Study ◽  
Median Serum

2053 Background: Interleukin-12 (IL-12), a master regulator of the immune system, results in anti-tumor responses in preclinical models, but safe use requires tightly controlled production. It was conditionally produced in Ph1 “main” study (NCT02026271) in subjects with recurrent glioblastoma (rGBM) using a replication-incompetent adenovirus modified to express IL-12 under transcriptional control of the proprietary RheoSwitch Therapeutic System (Ad-RTS-hIL-12, Ad) regulated by dose of veledimex (V). Monotherapy resulted in sustained intra-tumor influx of activated cytotoxic T cells, consistent with immune-mediated anti-tumor effect, improving overall survival (OS). This correlated with increased circulating CD8+/FoxP3+ T-cell ratio (“cytoindex”), an emerging biomarker of OS. While widely used with neurosurgery, dexamethasone (dex) blunts response to immunotherapies, nevertheless median mOS of subjects who received 20mg V of 12.7 mo (n=15) at 13.1 mo follow-up. However, subanalysis (n=6) showed low-dose dex (total ≤20 mg) during V dosing improved mOS (17.8 mo). We report a 36 subject substudy in rGBM with limited dex, total rGBM treated (n=70+). Methods: Ongoing Phase 1 substudy (NCT03679754) assesses safety and tolerability of local, inducible IL-12 by single intratumoral injection of Ad (2 x 1011 viral particles) + V (20 mg PO QD x15 doses Days 0-14) in subjects not receiving dex 4 wks prior to Ad. Results: As of 03Jan19, the majority of new subjects received low-dose dex (total ≤20mg Days 0-14). The initial impact of dex on mOS will be reported. As in the main study, Ad+V 20 mg respectively increased (median) serum IL-12 and downstream IFN-g from Days 0-3: 0.8 to 8.8 pg/mL and 0 to 8.6 pg/mL. Between Days 0-14, there was net increase in cytoindex (from 20 to 46). The safety profile was similar to the main study with the main adverse reaction (AR) being mild to moderate cytokine release syndrome (CRS) characterized by flu-like symptoms. No grade 4 CRS was noted; all ARs were manageable and reversable upon holding V. Conclusions: Local, controlled IL-12 production using the Ad + V platform in subjects with rGBM safely activates the immune system and when dex is limited, appears to further improve mOS, which warrants continued investigation. Clinical trial information: NCT03679754.

Promoting Stair Climbing in a Worksite and Public Setting: Are Footprints Enough?

2017 ◽  
Vol 32 (3) ◽  
pp. 527-535 ◽  
Author(s):  
Ann-Sophie Van Hoecke ◽  
Jan Seghers ◽  
Filip Boen
Keyword(s):  
Phase 1 ◽  
Interrupted Time Series ◽  
Stair Climbing ◽  
Health Message ◽  
Series Design ◽  
Public Setting ◽  
The Impact ◽  
A Company ◽  
Interrupted Time Series Design

Purpose: To evaluate the impact of footprints on stair climbing in different settings. Design: Interrupted time-series design. Setting: A company (stair/elevator choice) and a mall (stair/escalator choice). Participants: Employees (n = 5676) and visitors of the mall (n = 12 623). Intervention: An intervention comprising 3 consecutive phases was implemented—(1) footprints leading to the stairs were stuck on the floor, (2) a health message referring to the footprints was introduced, and (3) passersby were congratulated for their increased stair use. Measures: Stair climbing was observed before (ie, baseline), during, and 6 to 13 weeks after (ie, follow-up) the intervention. Analysis: Proportions of stair climbers were compared using χ2 analyses. Results: The footprints resulted in a closely significant increase in stair climbing in the company (from 27.7% at baseline to 31.2% in phase 1). However, they did not produce any effect in the mall. Introducing a health message yielded an additional 12.4% increase in stair climbing in the company and a significant 11.4% increase in the mall (22.3% in phase 2). Congratulating people did not further increase stair climbing. At follow-up, the proportions of stair climbers dropped but still exceeded baseline. Conclusion: Footprints tend to increase stair climbing in a worksite setting with a stair/escalator choice but not in a public setting with a stair/elevator choice. Adding a meaningful message seems essential to obtain stronger and longer term effects.

scholarly journals ATIM-25. PD-1 INHIBITION CAN BE COMBINED WITH IL-12 IN SUBJECTS WITH RECURRENT GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi6-vi7
Author(s):  
Ennio Chiocca ◽  
Rimas Lukas ◽  
Ganesh Rao ◽  
Jill Buck ◽  
Nathan Demars ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
Dose Escalation ◽  
Safety Profile ◽  
Adverse Reactions ◽  
Phase 1 ◽  
Recurrent Glioblastoma ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Main Study

Abstract Monotherapy with intratumoral Ad-RTS-hIL-12 (Ad), a novel gene therapeutic conditionally expressing IL-12 under the transcriptional control of oral veledimex (V, 20 mg) acting via the proprietary RheoSwitch Therapeutic System® (RTS®), was shown in a phase 1 Main study (NCT02026271) to elicit a sustained intra-tumoral activated cytotoxic T-cell response with co-expression of PD-1. Additionally, the Main study showed improved median overall survival (mOS), compared to historical controls, in subjects with recurrent glioblastoma (rGBM) receiving Ad + V. Herein, we report updated findings from on an ongoing open label, dose-escalation Phase 1 substudy (NCT03636477) evaluating safety and tolerability of local, controlled IL-12 plus nivolumab in adult subjects with rGBM. Ad was administered by single intratumoral injection (2 x 1011 viral particles) on Day 0 plus V (10 and 20 mg) PO QD x 15 with nivolumab (1 and 3mg/kg) IV on Days -7, 15, then Q2W. Subjects have been accrued into three cohorts and follow-up is ongoing. Data from all three cohorts regarding dose escalation of V and nivolumab will be presented. The initial safety profile during V dosing period was similar to Ad+V monotherapy with adverse reactions being dose-related and rapidly reversible upon discontinuation of V. And those adverse reactions during the follow on nivolumab dosing were tolerable and manageable and consistent with nivolumab labeling, with no synergistic toxicities, and drug-related deaths. In the first two cohorts (where data is available), combination therapy improved the biomarker “cytoindex” (ratio of circulating CD8+ T cells to FoxP3+ regulatory T cells). (In the Main study, cytoindex correlated with overall survival). Controlled IL-12 production using Ad+V with nivolumab is a rational combination with initial data consistent with immune-mediated anti-tumor effects with a favorable safety profile. Further phase 2 investigation of Ad+V plus a checkpoint inhibitor in rGBM is planned.

scholarly journals P094: Meeting patient expectations in the emergency department: preliminary findings from the preparing emergency patients and providers study

CJEM ◽  
2017 ◽  
Vol 19 (S1) ◽  
pp. S110
Author(s):  
J. Nunn ◽  
C. Cassidy ◽  
D. Chiasson ◽  
S. MacPhee ◽  
J. Curran
Keyword(s):  
Emergency Department ◽  
Response Rate ◽  
Phase 1 ◽  
Patient Expectations ◽  
Satisfaction With Care ◽  
Medical Encounter ◽  
X Ray ◽  
Phase Study ◽  
The Impact

Introduction: Effective communication to develop a shared understanding of patient expectations is critical in establishing a positive medical encounter in the emergency department (ED). However, there is limited research examining patient/caregiver expectations in the ED, and their impact on the beliefs, attitudes and behaviours during and after an ED visit. The objective of this study is to examine patient/caregiver expectations and satisfaction with care in the ED using a patient expectation questionnaire and a follow up survey. Methods: As a part of a larger 3-phase study on patient/caregiver expectations in adult and pediatric EDs, a 7-item, paper-based questionnaire was distributed to all patients and/or caregivers who presented to one of four EDs in Nova Scotia with a Canadian Triage and Acuity Scale (CTAS) score of 2 to 5. A follow-up survey was distributed to all willing participants via email to determine their satisfaction with care received in ED. Descriptive statistics were used to analyze responses. Results: Phase 1 was conducted from January to September 2016. In total, 24,788 expectation questionnaires were distributed to ED patients/caregivers, 11,571 were collected (47% response rate), and 509 patients were contacted for a follow-up survey. Preliminary analysis of 4,533 questionnaires shows the majority of patients (67.1%) made the decision by themselves to present to the ED, while others were advised by a family/friend (22%). Respondents were most worried about an injury (17.8%) followed by illness (15.6%) and expected to talk to a physician (69.9%) and receive an x-ray (39.3%). The majority of physicians (53.3%) reported the expectation tool helped in caring for the patient and 87.5% felt they met patient expectations. There were 147 patient/caregiver responses to a follow-up survey (29% response rate) and 87.1% of responders reported that ED clinicians met their expectations. Conclusion: Patient/caregivers have a variety of concerns, questions, and expectations when presenting to the ED. Obtaining expectations early in the patient encounter may provide opportunities for improved communication between clinicians and patients while enhancing satisfaction with care received. Further analysis is needed to determine the impact of the expectation questionnaire on productivity in the ED.

scholarly journals Examining the impact of a community-based exercise intervention on cardiorespiratory fitness, cardiovascular health, strength, flexibility and physical activity among adults living with HIV: A three-phased intervention study

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257639
Author(s):  
Kelly K. O’Brien ◽  
Aileen M. Davis ◽  
Soo Chan Carusone ◽  
Lisa Avery ◽  
Ada Tang ◽  
...  
Keyword(s):  
Physical Activity ◽  
Blood Pressure ◽  
Cardiovascular Health ◽  
Intervention Study ◽  
Phase 1 ◽  
Community Based ◽  
Phase 3 ◽  
Living With Hiv ◽  
The Impact

Purpose Our aim was to examine the impact of a community-based exercise (CBE) intervention on cardiorespiratory fitness, cardiovascular health, strength, flexibility, and physical activity outcomes among adults living with HIV. Methods We conducted a longitudinal intervention study with community-dwelling adults living with HIV in Toronto, Canada. We measured cardiopulmonary fitness (V̇O2peak (primary outcome), heart rate, blood pressure), strength (grip strength, vertical jump, back extension, push-ups, curl ups), flexibility (sit and reach test), and self-reported physical activity bimonthly across three phases. Phase 1 included baseline monitoring (8 months); Phase 2 included the CBE Intervention (6 months): participants were asked to exercise (aerobic, strength, balance and flexibility training) for 90 minutes, 3 times/week, with weekly supervised coaching at a community-based fitness centre; and Phase 3 included follow-up (8 months) where participants were expected to continue with thrice weekly exercise independently. We used segmented regression (adjusted for baseline age and sex) to assess the change in trend (slope) among phases. Our main estimates of effect were the estimated change in slope, relative to baseline values, over the 6 month CBE intervention. Results Of the 108 participants who initiated Phase 1, 80 (74%) started and 67/80 (84%) completed the intervention and 52/67 (77%) completed the study. Most participants were males (87%), with median age of 51 years (interquartile range (IQR): 45, 59). Participants reported a median of 4 concurrent health conditions in addition to HIV (IQR: 2,7). Participants attended a median of 18/25 (72%) weekly supervised sessions. Change in V̇O2peak attributed to the six-month Phase 2 CBE intervention was 0.56 ml/kg/min (95% Confidence Interval (CI): -1.27, 2.39). Significant effects of the intervention were observed for systolic blood pressure (-5.18 mmHg; 95% CI: -9.66, -0.71), push-ups (2.30 additional push-ups; 95% CI: 0.69, 3.91), curl ups (2.89 additional curl ups; 95% CI: 0.61, 5.17), and sit and reach test (1.74 cm; 95% CI: 0.21, 3.28). More participants engaged in self-reported strength (p<0.001) and flexibility (p = 0.02) physical activity at the end of intervention. During Phase 3 follow-up, there was a significant reduction in trend of benefits observed during the intervention phase for systolic blood pressure (1.52 mmHg/month; 95% CI: 0.67, 2.37) and sit and reach test (-0.42 cm/month; 95% CI: -0.68, -0.16). Conclusion Adults living with HIV who engaged in this six-month CBE intervention demonstrated inconclusive results in relation to V̇O2peak, and potential improvements in other outcomes of cardiovascular health, strength, flexibility and self-reported physical activity. Future research should consider features tailored to promote uptake and sustained engagement in independent exercise among adults living with HIV. ClinicalTrials.gov Identifier NCT02794415. https://clinicaltrials.gov/ct2/show/record/NCT02794415.

A psychosocial assessment and management tool for children and youth in crisis

CJEM ◽  
2018 ◽  
Vol 21 (1) ◽  
pp. 87-96 ◽  
Author(s):  
Alison Lee ◽  
Mariana Deevska ◽  
Karly Stillwell ◽  
Tyler Black ◽  
Garth Meckler ◽  
...  
Keyword(s):  
Emergency Department ◽  
Phase 1 ◽  
Pediatric Emergency ◽  
Psychosocial Assessment ◽  
Management Tool ◽  
Psychiatric Consultation ◽  
Pilot Implementation ◽  
Two Phases ◽  
The Impact

ABSTRACTObjectivesTo evaluate the psychometric properties of HEARTSMAP, an emergency psychosocial assessment and management tool, and its impact on patient care and flow measures.MethodsWe conducted the study in two phases: first validating the tool using extracted information from a retrospective cohort, then evaluating implementation on a prospective cohort of youth presenting with mental health complaints to a tertiary Pediatric Emergency Department (PED). In phase 1, six PED clinicians applied HEARTSMAP to extracted narratives and we calculated inter-rater agreement for referral recommendations using Cohen’s Kappa and the sensitivity and specificity for identifying youth requiring psychiatric consultation and hospitalization. In phase 2, PED clinicians prospectively used HEARTSMAP and we assessed the impact of the tool’s implementation on patient-related outcomes and Emergency department (ED) flow measures.ResultsWe found substantial agreement (κ=0.7) for cases requiring emergent psychiatric consultation and moderate agreement for cases requiring community urgent and non-urgent follow-up (κ=0.4 each). The sensitivity was 76% (95%CI: 63%, 90%) and specificity was 65% (95%CI: 55%, 71%) using retrospective cases. During pilot implementation, 62 patients received HEARTSMAP assessments: 46 (74%) of HEARTSMAP assessments triggered a recommendation for ED psychiatry assessment, 39 (63%) were evaluated by psychiatry and 13 (21%) were admitted. At follow-up, all patients with HEARTSMAP’s triggered recommendations had accessed community resources. For those hospitalized for further psychiatric care at their index or return visit within 30 days, 100% were initially identified by HEARTSMAP at the index visit as requiring ED psychiatric consultation.ConclusionsHEARTSMAP has strong reliability, and when applied prospectively is a safe and effective management tool.

scholarly journals CTIM-05. COMBINATION OF CONTROLLED INTERLEUKIN-12 GENE THERAPY WITH IMMUNE CHECKPOINT BLOCKADE IN RECURRENT GLIOBLASTOMA: UPDATED RESULTS OF A MULTI-INSTITUTIONAL, OPEN LABEL PHASE 1 TRIAL

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii33-ii33
Author(s):  
E Antonio Chiocca ◽  
Rimas Lukas ◽  
Clark Chen ◽  
Ganesh Rao ◽  
Christina Amidei ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Gene Therapy ◽  
T Cells ◽  
Immune Checkpoint ◽  
Phase 1 ◽  
Safety Data ◽  
Recurrent Glioblastoma ◽  
Interleukin 12 ◽  
Open Label ◽  
Phase 1 Trial

Abstract A published clinical trial of veledimex (V)-regulatable interleukin-12 (IL-12) gene therapy (“Controlled IL-12”) under the control of a transcriptional switch (RheoSwitch Therapeutic Systemâ, RTSâ) as monotherapy in recurrent glioblastoma (rGBM) showed sustained infiltration of activated T cells within the tumor months after treatment (Sci Transl Med. 2019;11(505)). These T cells demonstrated up-regulation of immune checkpoint signaling, providing a rationale for combination therapy with the PD-1 inhibitor, nivolumab (nivo). We report interim findings following completion of enrollment (with follow-up ongoing) for a multi-institutional, open label, dose-escalation phase 1 trial (NCT03636477) evaluating safety and tolerability of loco-regional Controlled IL-12 in combination with nivo in adults with rGBM. Replication-incompetent adenovirus coding for RTS-IL-12 (Ad) was administered during surgery by free-hand injection into the tumor and periphery (2 x 1011 viral particles, Day 0) accompanied by V (10 or 20 mg) PO QD x 15 (Days 0 to 14) in combination with nivo (1 or 3 mg/kg) IV on Days -7, 15, then Q2W. Twenty-one subjects were treated (Cohort 1: V 10 mg, nivo 1 mg/kg, n=3; Cohort 2: V 10 mg, nivo 3 mg/kg, n=3; and Cohort 3: V 20 mg, nivo 3 mg/kg, n=3 & 12 in expansion). Safety data were comparable to Ad+V monotherapy. Adverse reactions (ARs) during follow-on nivo dosing were consistent with nivo labeling. ARs were manageable and generally reversible with no synergistic toxicities. Updated overall survival findings will be presented. Baseline and post-treatment histochemical staining and multiplex immunofluorescence analyses for a subgroup of subjects will be discussed. The safety of this combination immunotherapy has been established, leading to a currently accruing phase 2 clinical trial of loco-regional Controlled IL-12 gene therapy in combination with the PD-1 inhibitor cemiplimab-rwlc (NCT 04006119).

scholarly journals P095: Preparing emergency patients and providers study: Clinician and patient satisfaction with communication tool

CJEM ◽  
2019 ◽  
Vol 21 (S1) ◽  
pp. S98
Author(s):  
J. Nunn ◽  
D. Chiasson ◽  
C. Cassidy ◽  
S. MacPhee ◽  
B. Rose-Davis ◽  
...  
Keyword(s):  
Nova Scotia ◽  
Response Rate ◽  
Phase 1 ◽  
Descriptive Statistics ◽  
Phase 2 ◽  
Phase 3 ◽  
Item Questionnaire ◽  
Ed Visits ◽  
The Impact

Introduction: Effective communication to develop a shared understanding of patient/caregiver (P/C) expectations is critical during emergency department (ED) encounters. However, there is limited research examining the use of communication tools of P/C expectations to improve communication in the ED. The objective of this study was to examine satisfaction with a patient expectations questionnaire, known as the PrEPP tool, and its impact on communication and management of patients in the ED. Methods: The PrEPP tool collected P/C expectations over 3 phases of the study. In phase1, the PrEPP tool was distributed to all P/Cs (CTAS score of 2 to 5) in four EDs in Nova Scotia. In phase 2 the PrEPP tool was refined to a 5-item questionnaire. In phase 3 the PrEPP tool was re-implemented over a six-month period. Follow-up surveys were distributed to P/Cs via email (phase 1, 3) and HCPs on iPads in the ED (phase 3) to determine the impact of the tool on communication and management of patients. Entries were compiled on a REDCap database and descriptive statistics were used to analyze responses related to satisfaction.The PrEPP tool collected P/C expectations over 3 phases of the study. In phase1, the PrEPP tool was distributed to all P/Cs (CTAS score of 2 to 5) in four EDs in Nova Scotia. In phase 2 the PrEPP tool was refined to a 5-item questionnaire. In phase 3 the PrEPP tool was re-implemented over a six-month period. Follow-up surveys were distributed to P/Cs via email (phase 1, 3) and HCPs on iPads in the ED (phase 3) to determine the impact of the tool on communication and management of patients. Entries were compiled on a REDCap database and descriptive statistics were used to analyze responses related to satisfaction. Results: In Phase 1, 11418 PrEPP tools and 147 surveys (29% response rate) were collected from January-June 2016. The majority of P/Cs found the PrEPP questionnaire easy to complete (95.9%) and felt HCPs met their expectations (87.1%). In Phase 3, 951 P/C (31.1% response rate) and 128 HCP surveys were collected. Of P/C respondents 45.9% felt PrEPP helped to communicate expectations, while 49.7% said that they would like to use it on future ED visits. The majority of P/C respondents (75.4%) indicated their expectations were met during their visit to the ED. Of those whose expectations were not met, 69% felt their expectations were not discussed. The majority of HCP respondents (90.4%) indicated they used the PrEPP tool at least sometimes. Also, 78.4% said it influenced patient communication and 42% indicated the tool influenced management of patients at least sometimes. Conclusion: Obtaining expectations early in the patient encounter may provide opportunities for improved communication in the ED. P/Cs found the PrEPP tool easy to use to communicate their expectations and HCPs felt it influenced communication and management of patients in the ED. Further qualitative thematic analysis is needed to explore how the PrEPP tool impacted ED visits.

scholarly journals Predicting the Development of Adult Nature Connection Through Nature Activities: Developing the Evaluating Nature Activities for Connection Tool

2021 ◽  
Vol 12 ◽  
Author(s):  
Victoria Carr ◽  
Joelene Hughes
Keyword(s):  
Behavioral Intentions ◽  
Phase 1 ◽  
Behavioral Outcomes ◽  
Incremental Validity ◽  
Short Term ◽  
Pilot Survey ◽  
Nature Connection ◽  
Conservation Organizations ◽  
The Impact

Nature Connection (NC) is considered an important driver of conservation behavior. Consequently, conservation organizations run many activities aiming to increase NC among participants. However, little is known about which activities are most effective at doing this and why. This study developed the Evaluating Nature Activities for Connection Tool (ENACT), to evaluate the effectiveness of activities for increasing participants’ NC and nature-related intentions. ENACT comprises 11 activity aspects identified through two research phases. In Phase 1, a literature search, focus group and interviews identified desired, short-term behavioral outcomes of nature activities, and variables that might promote these. In Phase 2, 241 adults completed a pilot survey immediately post-nature activity, with 1-month follow-up (N = 145), to evaluate the impact of participation on NC, nature-related behavioral intentions and behaviors. ENACT correlated with NC measures and offered incremental validity in predicting nature-related behavioral intentions and self-reported behaviors after 1 month.

scholarly journals ATIM-18. SURVIVAL OF SUBJECTS WITH RECURRENT GLIOBLASTOMA RECEIVING INTRA-TUMORAL ADMINISTRATION OF IL-12 MANAGED WITH LOW-DOSE DEXAMETHASONE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi5-vi5
Author(s):  
Rimas Lukas ◽  
Ennio Chiocca ◽  
Sylvia Kurz ◽  
John Yu ◽  
Joseph Landolfi ◽  
...  
Keyword(s):  
T Cells ◽  
Survival Data ◽  
Peripheral Blood ◽  
Low Dose ◽  
Phase 1 ◽  
Intratumoral Injection ◽  
Recurrent Glioblastoma ◽  
Biomarker Analysis ◽  
Gene Switch ◽  
Subject Characteristics

Abstract Ad-RTS-hIL-12 (Ad) is a novel gene therapy, conditionally expressing IL-12 via the RheoSwitch Therapeutic System® (RTS®) gene switch under control of an oral activator ligand, veledimex (V). We previously reported results from 51 subjects (NCT02026271 and NCT03679754) describing biological activity of controlled IL-12, safety and survival data. Previously, subjects who received Ad+V (20 mg) managed with low-dose dexamethasone in the Main study achieved a mOS of 17.8 months, which is approximately twice the anticipated survival compared to historical controls. The mechanism of action of Ad+V is based on controlled secretion of recombinant IL-12 (measured in peripheral blood as a surrogate for intra-tumor-production), downstream upregulation of endogenous IFN-g (measured in peripheral blood), and an increase in the “cytoindex” (ratio of circulating CD8+ T cells to FoxP3+ regulatory T cells), an emerging biomarker of overall survival. Herein we provide an update of subject characteristics, survival and biomarker analysis from the ongoing Phase 1 and expansion substudy. assessing safety and tolerability of local, inducible IL-12 by single intratumoral injection of Ad (2 x 1011 viral particles) + V (20 mg PO QD x15 doses Days 0–14) in subjects, including a subset receiving low-dose corticosteroids (≤20 mg cumulative dexamethasone Days 0–14). Drug-related toxicities were predictable, dose-related, and promptly reversible upon discontinuation of V with no drug-related deaths. Biomarker studies related to production of IL-12 and IFN-g, as well as cytoindex remain encouraging. As of 04Jun19, mOS in the Expansion substudy had not yet been reached (patient enrollment occurred from September 2018-February 2019). Most subjects (65%) received low-dose dexamethasone (cumulative ≤20mg Days 0–14); initial impact of this and other subject characteristics on survival will be presented.

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