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BACKGROUND Newly diagnosed glioblastoma (nGBM) has dismal outcomes with survival of 15-18 months. Tumor associated “survivin” is expressed in > 95% of nGBM and targetable by SurVaxM immunotherapy. METHODS nGBM patients (pts) were enrolled in this Phase 2 study, age ≥ 18, KPS ≥ 70, IHC confirmed surviving-expression, expression of HLA-A*02, A*03, A*11 or A*24 MHC-I alleles and residual contrast enhancement of ≤1 cm3 by MRI. Pts were treated with standard TMZ chemoradiation followed by initiation of 4 priming doses of SurVaxM (500 mcg in emulsion with Montanide ISA 51, every 2 weeks) with 100 mcg sargramostim. Maintenance doses of SurVaxM-Montanide plus sargramostim given every 12 weeks with Adjuvant TMZ for at least 6 cycles. The primary endpoint was 70% progression free survival (PFS) at 6 mos. Primary analyses of median PFS (mPFS) and median overall survival (OS) were measured from the first immunization. Safety, tolerability, and immune responsiveness were also determined. RESULTS 63 pts (38 males), median age, 60 years were treated at 5 sites. SurVaxM was well tolerated, with no serious adverse events. A strong positive correlation, accounting for censoring, was observed between PFS and OS of all pts (r = 0.79; 95% CI (0.66,0.87)). SurVaxM was immunogenic and produced survivin-specific CD8+ T-cells and antibody (IgG) titers in both methylated and unmethylated MGMT pts. Both groups showed clinical benefit with PFS of 11.4 months for the for the whole group, 7.0 months for unmethylated and 17.9 months for methylated group. OS of 25.9 months for the whole group, 16.5 months for unmethylated and 41.4 months for methylated group. CONCLUSIONS SurVaxM appeared to be safe and well-tolerated in pts with nGBM. SurVaxM was effective at stimulating survivin-specific immune responses and the primary endpoint was met. SurVaxM represents a promising therapy for nGBM, randomized trial is ongoing. Clinical trial information: NCT02455557.

BACKGROUND: Survivin is an anti-apoptotic protein that is highly expressed in glioblastoma (GBM). We conducted a single-arm, multi-center phase II trial in newly diagnosed GBM (nGBM) to determine 6-month progression-free survival (PFS-6), 12-month overall survival (OS-12) and immunologic response in patients treated with surgery, chemoradiation, adjuvant temozolomide (TMZ) and survivin-targeted immunization. METHODS: Patients with nGBM who hadwith HLA-A*02, -A*03, -A*11 and -A*24 haplotypes and, Karnofsky performance status ≥70 were included. Following craniotomy (3 residual contrast enhancement) and chemoradiation, patients received 4 prime-boost doses of SurVaxM (500 mcg) every 2 weeks, followed by adjuvant TMZ and maintenance SurVaxM every 12 weeks until progression. Immunogenicity of SurVaxM was assessed by measuring anti-survivin antibody levels and survivin-specific CD8+ T-cells using multimers. RESULTS: Sixty-three patients, median age 60 years (range, 20–82), including 38 males were treated. Survivin expression was detectable in all patients (1–40% ([median = 12%]) of tumor cells by immunohistochemistry). The vaccine was highly immunogenic and produced survivin-specific CD8+ T-cells and antibody (IgG) titers. The regimen was well-tolerated and immunogen-related adverse events were mild with no regimen limiting toxicity attributable to SurVaxM. PFS-6 was 96.7% (C.I. = 87.6%- 99.1%) and OS-12 was 94.2% (C.I. =83.0%-98.1%) as measured from diagnosis. In MGMT methylated, PFS6 of 96.9% (C.I. = 99.6% to 79.8%); OS12 of 98.1% (C.I. = 99.0% to 97.2%) and in unmethylated tumors, PFS6 of 96.6% (C.I. = 99.6% to 78%); OS12 of 88.9% (C.I. = 99% to 77.2%) was observed. Methylated patients with higher survivin levels had significantly better PFS-6 than those with low survivin levels (r = 0.4). CONCLUSIONS: SurVaxM is safe and a promising adjunct therapy in nGBM. Compared to historical matched controls, addition of SurVaxM improved PFS-6 and OS-12 in nGBM. Patients with poor prognostic factors (unmethylated MGMT, higher survivin levels) treated with SurVaxM achieved better survival than expected.

2016 Background: SVN53-67/M57-KLH (SurVaxM) is a novel cancer vaccine designed to stimulate an immune response targeting the tumor-specific antigen survivin. A multi-center, single-arm phase 2 clinical trial of SurVaxM in survivin-positive newly diagnosed glioblastoma (nGBM, NCT02455557) is now fully enrolled and data updated. Methods: Patients (n = 63) with nGBM were enrolled at 5 US cancer centers and followed for safety, 6-month progression-free survival (PFS6), 12-month overall survival (OS12) and immunologic response. All patients underwent craniotomy with near-total resection ( < 1 cm3 residual contrast enhancement), TMZ chemoradiation, adjuvant TMZ and SurVaxM. Patients received 4 doses of SurVaxM (500 mcg) in Montanide with sargramostim (100 mcg) biweekly, followed by maintenance SurVaxM with adjuvants every 12 weeks until tumor progression. Immunogenicity of SurVaxM was assessed by detection of survivin-specific antibody (IgG) and CD8+ T-cell levels. Results: Median age was 60 yrs (range, 20-82), 53% methylated MGMT, 46% unmethylated MGMT (1 N/A) and 60% were male. Survivin expression ranged from 1-40% (median 12%) by immunohistochemistry. Median time to first immunization was 3.0 mo (1.9-4.0 mo) from diagnosis. There have been no RLT or grade ≥ 3 SAE attributable to SurVaxM. The most common AE was grade 1-2 injection site reactions. OS12 was 86% from first immunization and 93.4% from diagnosis. OS12 for meMGMT was 93.1% and unMGMT was 78% from first immunization. Median time to tumor progression (mPFS) was 13.9 months from diagnosis. Median OS has not yet been reached. SurVaxM produced an increase in survivin-specific IgG titre from pre-vaccine baseline to ≥ 1:10,000 in 67% of pts and ≥ 1:100,000 in 27%. CD8+ T cell responses were observed. Anti-survivin IgG and OS were correlated. Conclusions: SurVaxM immunotherapy generated encouraging efficacy and immunogenicity in nGBM and has minimal toxicity. A randomized, prospective trial of SurVaxM in nGBM is planned. Clinical trial information: NCT024455557.

Purpose/objectives To explore the survivor experience of adults who have been diagnosed three years or longer with a primary malignant brain tumor (PMBT). Research approach Qualitative using a biographical narrative approach. Setting Six sites across the United States. Participants Survivors of PMBTs (N = 35) and their family caregivers (N = 35). Methodologic approach Using a semistructured interview guide, survivors and caregivers were interviewed individually about their lives before and since the PMBT diagnosis. Thematic analysis was performed to identify themes. Findings Stability in survivor lives disintegrated as a result of the changes experienced related to the tumor and its treatment. Those changes were profound and ultimately contributed to multiple losses in key areas of their lives. Over time, living with the diagnosis and its consequences required survivors and their caregivers to adapt to the new reality of their lives. Through the process of becoming a survivor, individuals were able to take back control of their lives. Adaptation required survivors to use internal and external resources as ways of coping with their new reality. Conclusions People with PMBTs require support as they adapt to losses and changes that impact their lives. Assessment of specific changes that impact survivors' lives may be useful in guiding type of support given. Symptom management and mobilization of internal and external resources may lessen the life-changing impact. Interpretation Nurses should capture symptom meaning during assessments and expand assessments to include social support systems. Instituting measures that facilitate survivor independence may lessen the impact of disability. The significance of symptom worsening over time requires additional research. Knowledge translation Restoring self-worth and taking control of their lives are critical concerns for survivors of PMBTs.

2041Background: To determine 6-month progression-free survival (PFS-6), 12-month overall survival (OS-12) and immunologic response in newly diagnosed glioblastoma (nGBM) treated with concurrent tem...

Over the past 16 years, there has been an explosion of knowledge in the field of monoclonal antibody technology. There is an enormous potential for the use of monoclonal antibodies in the diagnosis and treatment of malignancies, and many clinical trials are under way. This paper serves as an introduction to monoclonal antibody concepts for the oncology nurse. Antibody/antigen principles, production of monoclonal antibodies, common side effects of use, and nursing implications are discussed. Results of a recent clinical trial and a patient case study are used to illustrate the application of radiolabeled monoclonal antibodies as a cancer diagnostic technique.

Background: Recent studies using SurVaxM, a survivin based multi-epitope cryptic peptide mimic, show specific CD8+ T cell responses and specific CD4+ T cell stimulation. Currently SurVaxM has completed a phase I clinical trial designed to study its safety, tolerability and immunological effects in patients with survivin-positive recurrent malignant gliomas. Survivin is an intracellular inhibitor of apoptosis protein (IAP) that mediates a number of anti-apoptotic and oncogenic effects and is highly expressed in malignant gliomas and other cancers. The vaccine is immunogenic in humans with HLA-A*02, HLA-A*03, HLA-A*24 and other haplotypes and pre-clinical studies demonstrate potent and specific cytokine-supported antitumor CTL responses. Methods: Nine patients with survivin-positive, recurrent malignant gliomas and either HLA-A*02 or HLA-A*03 haplotypes received a series of 4 subcutaneous injections of SurVaxM at 2 week intervals. MRIs were performed at baseline, week 8, and at subsequent intervals. Results: SurVaxM was well tolerated with no SAE related to vaccine administration. Most AE were grade 1, including 6 of 9 patients with grade 1 localized erythema at the injection site. Three patients reported grades 1 or 2 fatigue, 2/9 experienced myalgia, possibly related to the study drug. Grade 1 lymphopenia was seen in 3/9 patients and grade 1 or 2 leukopenia was recorded in 3 patients. The only grade 3 AE, a seizure, was not related to the vaccine. The majority of patients developed specific cellular and humoral immune responses to survivin and 3 of 8 patients (all with recurrent glioblastoma), who are evaluable for clinical response, had stable disease after 17-26 months of ongoing follow-up. Five others have had progressive disease, although 4 of these maintained stable disease for 8-14 months. Conclusion: This study demonstrated the safety and tolerability of SurVaxM in patients with recurrent or progressive malignant glioma following failure of standard therapy. SurVaxM proved to be immunogenic in most patients. By activating multiple CD8+ CTL responses and CD4+ helper support, SurVaxM has a significant theoretical advantage as an active specific immunogen compared with survivin vaccines using a single class I-restricted peptide, or ones that incorporate generic helper peptides, which produce non-specific helper support. Early indicators point to a strong rationale for continued study. A phase II clinical trial of SurVaxM is planned. Citation Format: Michael J. Ciesielski, Laszlo Mechtler, Kathleen Mogensen, Jingxin Qiu, Manmeet Ahluwalia, Kelvin Lee, Alex Adjei, Robert Fenstermaker. Phase I study of SurVaxM in patients with survivin-expressing recurrent malignant gliomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT301. doi:10.1158/1538-7445.AM2015-CT301

BACKGROUND: Survivin is an inhibitor of apoptosis protein (IAP) that is highly expressed in malignant gliomas and other cancers. Induction of cytotoxic immunity against survivin is an attractive antitumor strategy. Preclinical studies demonstrated the ability of a KLH-conjugated survivin peptide mimic (SVN53-67/M57-KLH; SurVaxM) to induce an immune response capable of inhibiting the growth of gliomas in mice, and killing human glioma cells ex vivo. The vaccine is predicted to be immunogenic in humans with HLA-A*02, HLA-A*03, HLA-A*24 and other haplotypes and pre-clinical studies demonstrate potent and specific cytokine-supported antitumor CTL responses. METHODS: Nine patients with survivin-positive, recurrent malignant gliomas and either HLA-A*02 or HLA-A*03 haplotypes received a series of 4 subcutaneous injections of SurVaxM at 2 week intervals. MRIs were performed at baseline, week 8, and at subsequent intervals. RESULTS: SurVaxM was well tolerated with no SAE, and mostly grade one AE. 6 of 9 patients experienced grade 1 localized erythema at the injection site, likely related to the vaccine. 3 patients reported grades 1 or 2 fatigue, 2/9 experienced myalgia, possibly related to the study drug. Grade 1 lymphopenia was seen in 3/9 patients and grade 1 or 2 leukopenia was recorded in 3 patients. The only grade 3 AE, a seizure, was not related to the vaccine. The majority of patients developed specific cellular and humoral immune responses to survivin and 3 of 8 patients (all with GBM), who are evaluable for clinical response, have stable disease after more than 12 months of follow-up. All others have had progressive disease. Survival data will be described. CONCLUSION: This study demonstrated the safety and tolerability of SurVaxM in patients with recurrent or progressive malignant glioma following failure of standard therapy. SurVaxM proved to be immunogenic in most patients. A phase II clinical trial of SurVaxM is planned.