42 research outputs found
Abstract CT114: The MITCI (Phase 1b) study: A novel immunotherapy combination of intralesional Coxsackievirus A21 and systemic ipilimumab in advanced melanoma patients with or without previous immune checkpoint therapy treatment
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Background: CAVATAKTM is a novel bio-selected oncolytic and immunotherapeutic strain of Coxsackievirus A21 (CVA21). In a phase 2 study, intratumoral (i.t.) CVA21 injection of advanced melanoma lesions resulted in increases in tumor immune-cell infiltration, up-regulation of γ-INF response and immune-checkpoint genes, including CD122 which may be a potential prognostic marker for enhanced anti-tumor activity by anti-CTLA-4 blockade strategies. Intratumoral replication of CAVATAK may act as a strong “immune-sequestration signal” to circulating activated T-cells following CTLA-4 blockade. We present the preliminary data of the open-label, Phase Ib MITCI (Melanoma Intra-Tumoral Cavatak and Ipilimumab) study of novel immunotherapy combination Coxsackievirus A21 and ipilimumab in patients (pts) with advanced melanoma.
Methods: The Phase Ib MITCI study (NCT02307149) is investigating the efficacy and safety of i.t. CVA21 and i.v. ipilimumab in up to 50 pts with treated or untreated unresectable Stage IIIC-IVM1c melanoma. Pts received up to 3 x 108 TCID50 CVA21 i.t. on study days 1, 3, 5, 8 and 22, and then q3w for a further 6 series of injections. Ipilimumab (3 mg/kg) q3w was given as 4 i.v. infusions starting at Day 22. The first response assessment (irWHO) occurred at study Day 106. The primary endpoint was to assess safety of CVA21 in combination with ipilimumab treatment.
Results: At present no DLT’s have been reported in the 23 pts currently enrolled. Combination treatment has been generally well-tolerated with surprisingly only one Gr 3 or higher treatment-related AE being ipilimumab-related fatigue. The study met its primary statistical futility endpoint of achieving ≥ 4 confirmed objective responses (CR or PR) in the first 12 pts enrolled. Currently, of the first 18 pts eligible for investigator response assessment, the confirmed ORR for the ITT population is 50.0% (9/18), with the ORR for immune checkpoint-naïve pts being 60% (6/10) and previous immune checkpoint therapy pts being 38% (3/8). Of note, is the encouraging ORR of 57.1% (4/7 pts) in pts with stage IVm1c disease. The DCR (CR+PR+SD) on the ITT population is currently 78% (14/18) of which 66% of patients have been administered prior systemic therapy(s) with DCR of 100% (7/7) in pts with stage IVm1c disease. All responses were observed by 3.5 mths with complete tumor responses being observed in individual injected and non-injected lesions. Preliminary immune monitoring has indicated that CVA21 + ipilimumab increases the % of activated CD8 and CD4 T-cells with effector and memory phenotypes in the peripheral blood. The greatest increases in activated T cells in the peripheral blood occurred after the third ipilimumab dose.
Conclusions: Treatment of pts with CVA21 and ipilimumab has demonstrated durable response with minimal toxicity. The combination immunotherapy treatment has displayed anti-tumor activity in local, visceral and non-visceral lesions. The preliminary ORR rate for the ITT population of 50.0% is higher than published rates for either agent used alone (CVA21: ~28% and ipilimumab :~15-20%) in advanced melanoma patients. Finally, responses are observed in pts with PD following immune checkpoint inhibitor therapy, suggesting the additive therapeutic benefit of CVA21 with ipilimumab.
Citation Format: Brendan Curti, Jon Richards, Sigrun Hallmeyer, Mark Faries, Robert Andtbacka, Greg Daniels, Mark Grose, Darren R. Shafren. The MITCI (Phase 1b) study: A novel immunotherapy combination of intralesional Coxsackievirus A21 and systemic ipilimumab in advanced melanoma patients with or without previous immune checkpoint therapy treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT114. doi:10.1158/1538-7445.AM2017-CT114</jats:p
Positive Behavior Intervention Support Handbook for Paraeducators
No full textChallenging behaviors in the classroom can be taxing on everyone in the classroom. When behavioral needs are not met, academics can decline. Maintaining a safe and ready to learn environment requires meeting behavioral needs of all students, from minor behavior disruptions such as side talk and being out of seat to major disruptions such as yelling, refusal of work, and any unsafe behaviors. These challenging behaviors can happen in special and general education classrooms and the staff members who have a front row seat to these behaviors are paraeducators. Paraeducators are staples in the classroom, supporting students academically and behaviorally and they may often have limited resources to manage these behaviors. In order to provide paraeducators with more resources, the author aligned Positive Behavior Intervention Support (PBIS) and Win-Win Discipline (Kagan, Kyle, & Scott, 2004) in order to create a handbook for paraeducators focusing on how to best support students with challenging behaviors. The handbook provides an overview of PBIS, brief description of each Tier of the Multi-Tiered System of Support (MTSS), supports used in each Tier, and worksheets that paraeducators can use throughout the day. The author’s goal is to provide paraeducators with more support and resources in supporting students with challenging behaviors in the classroom and throughout their daily interactions
Abstract CT214: Phase II CALM study: Changes in the tumor microenvironment induced by the immunotherapeutic agent coxsackievirus A21 delivered intratumorally in patients with advanced melanoma
No full textManagement of Breast Cancer during Pregnancy: Are We Compliant with Current Guidelines?
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Introduction The purpose of this study was to evaluate the management of patients with breast cancer in pregnancy treated at the Advocate Health Care, to determine whether these patients were treated according to guidelines for pregnant patients, which aim to maximize both fetal and maternal outcomes.
Methods A retrospective chart review was performed at the Advocate Lutheran General Hospital, Christ Medical Center, and Illinois Masonic Medical Center from 2002 to 2012 on patients diagnosed with breast cancer during pregnancy using ICD-9 (International Classification of Diseases - 9th version) codes.
Results Eleven patients between 12 and 37 weeks' gestation matched the search criteria. One patient terminated the pregnancy. Patients in our study were treated appropriately according to guidelines with the following exceptions. Trastuzumab was used in one patient during pregnancy which likely caused the oligohydramnios resulting in an induction of labor at 33 weeks. Three patients were delivered preterm between 34 and 36 weeks without an obstetric indication. Two patients underwent sentinel node biopsy.
Conclusion The diagnosis of breast cancer in pregnancy is an infrequent but devastating diagnosis that is likely to increase. Although sentinel lymph node biopsy is not generally recommended in pregnancy, this may be an outdated guideline as using a low-dose lymphoscintigraphic technique appears to be safe in pregnancy.</jats:p
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381 Intratumoral oncolytic virus V937 plus ipilimumab in patients with advanced melanoma: the phase 1b MITCI study
No full textBackgroundIntratumoral administration of V937, a bioselected genetically unmodified Coxsackievirus A21, has shown antitumor activity both as a monotherapy and in combination with the anti–PD-1 antibody pembrolizumab.1–3 V937 induces lytic tumor cell infection and upregulation of members of immune checkpoint pathways.2 We present the results from the phase 1b MITCI study that evaluated V937 plus ipilimumab for advanced melanoma.MethodsEligible patients had unresectable or metastatic stage IIIB/C or IV melanoma amenable to intratumoral injection. Patients received intratumoral V937 3×108 TCID50 on days 1, 3, 5, 8, and 22, then Q3W for 14 more injections plus intravenous ipilimumab 3 mg/kg Q3W administered 4 times starting on day 22. Imaging was done Q6W beginning at day 106; response was assessed per immune-related response criteria (irRC). The primary endpoints were safety and ORR in the overall population and in patients whose disease progressed on prior anti–PD-1 therapy.Results50 patients were enrolled and received ≥1 dose of study treatment. At data cutoff (February 21, 2020), all had discontinued the study and study therapy. Median (range) age was 64.5 (28–88) years. Fourteen patients (28%) had stage III disease. Forty patients (80%) had received prior systemic treatment, 33 of whom had received anti–PD-1 therapy. The median number of cycles of ipilimumab was 4 (range, 1–4), and the number of intratumoral injections of V937 was 9 (range, 5–19). Among the 94% of patients who had ≥1 treatment-related AE, 14% had grade 3/4 treatment-related AEs, none of which were considered related to V937. The most common grade 3/4 treatment-related AEs were dehydration, diarrhea, and hepatotoxicity (4% each). No grade 5 treatment-related AEs occurred. The most common treatment-related AEs were pruritus (50%), fatigue (44%), diarrhea (32%), and nausea (22%). Efficacy outcomes for the overall population and by prior anti-PD-1 therapy use are presented in table 1. Tumor regression was observed in injected and noninjected lesions.Abstract 381 Table 1ConclusionsV937 plus ipilimumab was safe and the toxicities were manageable and consistent with that anticipated for the individual treatment components. ORR was robust and significantly higher than anticipated with ipilimumab monotherapy, including in patients who had received prior anti–PD-1 therapy. Most responses were durable (≥26 weeks), and responses seen in noninjected metastases provided evidence of probable systemic immune activation. The combination of V937 plus ipilimumab warrants further investigation in a larger trial in patients with advanced melanoma.AcknowledgementsMedical writing assistance was provided by Kathleen Estes, PhD, of ICON plc (North Wales, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationNCT02307149ReferencesPandha H, Harrington K, Ralph C, Melcher A, Gupta S, Akerley W, et al. Abstract CT115: phase 1b KEYNOTE 200 (STORM study): a study of an intravenously delivered oncolytic virus, coxsackievirus A21 in combination with pembrolizumab in advanced cancer patients. Cancer Res 2017;77(13 suppl):CT115.Andtbacka RHI, Curti BD, Kaufman H, Nemunaitis JJ, Daniels GA, Hallmeyer S, et al. Dynamics of tumor response in advanced melanoma patients treated with coxsackievirus A21. J Clin Oncol 2016;34(15 suppl):9553.Silk AW, Kaufman H, Gabrail N, Mehnert J, Bryan J, Norrell J, et al. Phase 1b study of intratumoral coxsackievirus A21 (CVA21) and systemic pembrolizumab in advanced melanoma patients: interim results of the CAPRA clinical trial. Cancer Res 2017;77(13 suppl):CT026.Ethics ApprovalAn independent institutional review board or ethics committee approved the protocol at each study site, and the trial was conducted in compliance with Good Clinical Practice guidelines and the Declaration of Helsinki. All patients provided informed consent
Abstract PO4-11-11: Provider perceptions of the POSITIVE trial, endocrine therapy interruption, and fertility preservation
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