Opera Studies Research Articles

A Comparative Analysis on the Relationship Between Artistic Creativity and Career Development in Chinese and Japanese Traditional Performing Arts

This research shows how different educational forms such as schooling and apprenticeship are related to the development of artistic creativity from the interdisciplinary perspective based on educational anthropology of performing arts and management studies. This topic has been insufficiently explored by previous studies in both fields. More specifically, by applying the concept of schoolnization, the research compares two contrasting case studies of Chinese Qin opera and Japanese Nohgaku, based on first-hand data acquired from years of ethnographic research, to formulate a hypothesis on the ideal relationship between the enhancement of artistic creativity and process of career development. The hypothesis serves as a practical analytical framework for future research in the field.

On the Problem of the Concept of "Topos" in Musicology (on the Example of A. Kholminov's Opera "Anna Snegina")

The purpose of the article is to consider the opera by A. N. Kholminov "Anna Snegina", applying the concept of "topos". In the center of the plot is the image of the poet Yesenin. To comprehend historical events through the iconic image of the epoch became for the composer a direct expression of the author's ideas. Borrowed from literary criticism, the category of "topos" allowed us to reveal the stylistic features of Kholminov's operatic language. The perspective of the proposed research will make an additional contribution to the list of works on the study of Russian opera, which determines the relevance of this article. A detailed study of the concept of "topos" in the humanities opens up great prospects for its application in relation to musical works. Scientific novelty is connected with the problem under study. Insufficient research on this issue prompts a thesis to turn to the term in its primary meaning and determines the relevance of its functioning in musicology. For the first time, A. N. Kholminov's opera is analyzed by means of such a concept as "topos". In this article, an attempt is made to apply the concept of "topos" to study the complex of musical and expressive means. As a result of the research, the author comes to the conclusion that the principles of fundamental importance in the analysis of the text in literary studies take place in the study of the artistic world of the opera "Anna Snegina" by A. N. Kholminov.

Grand Illusion: Phantasmagoria in Nineteenth-Century Opera, by Gabriela Cruz

<i>Grand Illusion: Phantasmagoria in Nineteenth-Century Opera</i>, by Gabriela Cruz

POSA392 Opera Study: Observatory of a Population Eligible to a Reintervention of a Bariatric Surgery in France- Impact of the Different Revisional Bariatric Surgeries on Diabetes Mellitus and Its Treatments.

POSA392 Opera Study: Observatory of a Population Eligible to a Reintervention of a Bariatric Surgery in France- Impact of the Different Revisional Bariatric Surgeries on Diabetes Mellitus and Its Treatments.

MELODY AS A FACTOR OF VOCAL AND PERFORMING INTERPRETATION OF THE OPERA IMAGE

The aim of the article is to determine current approaches to the phenomenon of opera melodics, clarify the concept of opera melody, substantiate the priority of vocal and performing interpretation in the formation of an opera image and in the development of an opera musical text. A comprehensive methodology for studying the genre nature of opera and its typological artistic features is proposed. The combination of textual and semantic approaches makes it possible to expand the understanding of the melodic functions of an opera text and its communicative tasks. The scientific novelty of the research is due to the identification of aesthetic, structural and compositional, artistic and psychological prerequisites for the creation of the theory of opera melos as an autonomous discipline that can influence modern opera studies and the creative practice of opera performers. The conclusions of the article indicate the key properties of the opera melody, which make it possible to characterize it as a way of creating an opera speech; emphasize the main factors of the opera melodic speech: the enlargement of the elements of the theme and the strengthening of its discreteness, the altitude-rhythmic fixation of the motivational relief, which makes it possible to convey the sound and content of the word, orientation on the “image of feeling”, emotional fullness and psychological personal reasoning, the requirement of getting used to and rebirth into an opera image and specific timbre predestination, that is, being attached to a certain type of vocal voice.

Made in Italy, tailored for Danes: Giuseppe Sarti and Italian Opera in Copenhagen

Abstract The institutionalization of a permanent Italian opera house in Copenhagen happened comparatively late for a European capital. The emergence of a new bourgeois audience, which for the first time shared loges with the aristocracy, created political and aesthetic turmoil linked to the politics of ‘Danishness’, Italophobia and anti-opera sentiment. This study focuses on Giuseppe Sarti, the first director of the opera in Copenhagen, and his strategies to adapt and translate opera for local audiences. The study examines connections between aesthetics, nationalism, and politics in Enlightenment Copenhagen. Bringing this perspective from the North into the study of opera in the age of reform allows us to understand not only the local context, but also the general processes by which Italian opera was adapted, produced, and consumed outside Italy—and the problems faced by the diaspora of Italian musicians to Europe’s Northern periphery.

Nighttime ambulatory pulse pressure predicts cardiovascular and all-cause mortality among middle-aged participants in the 21-year follow-up.

Office pulse pressure (PP) is a predictor for cardiovascular (CV) events and mortality. Our aim was to evaluate ambulatory PP as a long‐term risk factor in a random cohort of middle‐aged participants. The Opera study took place in years 1991–1993, with a 24‐h ambulatory blood pressure measurement (ABPM) performed to 900 participants. The end‐points were non‐fatal and fatal CV events, and deaths of all‐causes. Follow‐up period, until the first event or until the end of the year 2014, was 21.1 years (mean). Of 900 participants, 22.6% died (29.6% of men/15.6% of women, p<.001). A CV event was experienced by 208 participants (23.1%), 68.3% of them were male (p<.001). High nighttime ambulatory PP predicted independently CV mortality (hazard ratio [HR] 2.60; 95% confidence interval [CI 95%] 1.08–6.31, p=.034) and all‐cause mortality in the whole population (HR 1.72; Cl 95% 1.06–2.78, p=.028). In males, both 24‐h PP and nighttime PP associated with CV mortality and all‐cause mortality (24‐h PP HR for CV mortality 2.98; CI 95% 1.11–8.04, p=.031 and all‐cause mortality HR 2.40; CI 95% 1.32–4.37, p=.004). Accordingly, nighttime PP; HR for CV mortality 3.13; CI 95% 1.14–8.56, p=.026, and for all‐cause mortality HR 2.26; CI 95% 1.29–3.96, p=.004. Cox regression analyses were adjusted by sex, CV risk factors, and appropriate ambulatory mean systolic BP. In our study, high ambulatory nighttime PP was detected as a long‐term risk factor for CV and all‐cause mortality in middle‐aged individuals.

Efficacy and safety of ocrelizumab vs interferon beta-1a in participants of African descent with relapsing multiple sclerosis in the Phase III OPERA I and OPERA II studies

BackgroundPeople of African descent with multiple sclerosis (MS) appear to have a more severe disease course and may have an attenuated response to some medications compared with people of European descent. MethodsThis is a post hoc subgroup analysis of participants of African descent with relapsing forms of MS who were enrolled in the Phase III OPERA I or OPERA II clinical trials and treated with ocrelizumab (OCR) 600 mg every 6 months or interferon beta-1a (IFN β-1a) 44 μg 3 times per week. ResultsAmong the 1,656 participants enrolled in OPERA I and II, 72 (4.3%) were of African descent (OCR, 40; IFN β-1a, 32). A trend for reduction in annualized relapse rate (ARR) was observed in participants of African descent, with an ≈50% reduction with OCR vs IFN β-1a. The relative rate of the mean number of gadolinium-enhancing lesions on magnetic resonance imaging (MRI) was 0.04 (95% CI, 0.01–0.22; p=0.001) in participants of African descent treated with OCR compared with IFN β-1a. Similarly, the relative rate of the number of new or enlarging T2 lesions on MRI was 0.14 (95% CI, 0.06–0.32; p<0.001). In participants of African descent, those treated with OCR were 2.61 times more likely than those who received IFN β-1a to be classified as having no evidence of disease activity (95% CI, 1.24–5.49; p=0.003) and 4.17 times more likely to be classified as having no evidence of disease activity or progression (95% CI, 1.27–13.65; p=0.006). African-descent participants tended to have a greater radiographic burden of disease at baseline, develop more brain lesions when treated with IFN β-1a, and be at greater risk of disability progression than non–African-descent participants. Participants of African descent experienced slightly more adverse events, serious adverse events, and hypersensitivity reactions than non–African-descent participants. ConclusionIn this small sample of participants of African descent with relapsing MS from the OPERA studies, OCR demonstrated treatment benefits in clinical, MRI, and composite efficacy outcomes vs IFN β-1a, consistent with what was observed in the complete OPERA intention-to-treat cohorts.

Abstract PS13-16: Pharmacokinetic evaluation of an oral paclitaxel DHP107 (Liporaxel®) in patients with recurrent or metastatic breast cancer (MBC): Phase II study (OPERA, NCT03326102)

Abstract Background: Paclitaxel is a microtubule stabilizing anticancer therapy used to treat multiple cancers including breast cancer. DHP107 is an oral paclitaxel solubilized in lipid components using DaeHwa-Lipid bAsed Self-Emulsifying Drug delivery system (DH-LASED) technology. It demonstrated comparable efficacy and safety to IV paclitaxel in a phase 3 study for patients with advanced gastric cancer (Ann Oncol 2018) leading to regulatory approval in Korea, and also met the primary endpoint (ORR 54.5%) as first-line therapy (ESMO 2019) in the OPTIMAL Phase II study in patients with HER2 negative metastatic breast cancer (MBC). The confirmatory OPTIMAL Phase III study is ongoing in Asia and Europe. The OPERA Phase II study was designed as multinational, multicenter, randomized, open-label study to establish pharmacokinetic (PK) profile and efficacy of DHP107 in patients with MBC in the U.S. Method: A total of 72 patients with metastatic HER2 negative (HR+/HER2- or triple-negative breast cancer (TNBC)) will be randomized in a 2:1 fashion to receive DHP107 (200mg/m2 orally twice a day on Days 1, 8, and 15 in a 28-day cycle) or IV paclitaxel (80 mg/m2 on Days 1, 8, and 15 in a 28-day cycle) until disease progression or unacceptable toxicity. Tumor assessments are performed every 8 weeks. PK analyses were performed in a subset of patients receiving DHP107. A total of 103 blood samples were collected on Day 1 of Cycle 1 at predose and 1, 2, 3, 4, 6, and 10 hours post dose (before the 2nd dose administration on Day 1), and at predose on Day 8 of Cycle 1. All PK parameters were calculated by non-compartmental analysis using Phoenix WinNonlin version® 8.1. Results: A total of 13 subjects were enrolled in the PK substudy, All 13 patients were female and of Caucasian, non-Hispanic, ethnicity. Median Tmax was 2.17 h (range 1.92-4.08). Mean Cmax and AUC0-10h and their coefficient of variations (CV) were 330 ng/mL (31.1%) and 1233 ng·h/mL (30.3%), respectively (Table 1). The PK parameters of DHP107 were similar to those in a previous Phase I study in Korean cancer patients where Cmax and AUC0-48h were 235 ng/mL (43.9%) and 1348 ng·h/mL (19.7%) (Invest New Drugs 2012). Conclusion: PK profiles were well characterized from plasma concentrations in 13 Caucasian patients with MBC up to 10 hours after oral 200mg/m2 BID administration. DHP107 was rapidly absorbed and eliminated and inter-individual variability in exposure such as Cmax and AUClast was considered low. Compared to previous phase I PK results in Korean patients, Cmax and AUC parameters were similar after dosing with DHP107, demonstrating no clinically significant differences between Asian and Caucasian patients. Safety and efficacy will be evaluated in the ongoing OPERA and OPTIMAL studies. Table 1StatisticTmax(h)Cmax(ng/mL)AUClast, 0-10h(ngh/mL)AUCinf(ngh/mL)N13131311Mean(SD)330(103)1233(374)1462(411)CV%31.130.328.1Median[Min-Max]2.17[1.92-4.08] Citation Format: Hope S Rugo, Timothy J Pluard, Priyanka Sharma, Michelle Melisko, Ghassan Al-Jazayrly, Neelima Vidula, Yan Ji, David Weng, Hyeong-Seok Lim, Koung Eun Yoon, Hyun Ju Cho. Pharmacokinetic evaluation of an oral paclitaxel DHP107 (Liporaxel®) in patients with recurrent or metastatic breast cancer (MBC): Phase II study (OPERA, NCT03326102) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-16.

Validation of the adjusted multi-biomarker disease activity score as a prognostic test for radiographic progression in rheumatoid arthritis: a combined analysis of multiple studies

BackgroundThe multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors.MethodsFour cohorts were analyzed: the BRASS and Leiden registries and the OPERA and SWEFOT studies (total N = 953). Treatments included conventional DMARDs and anti-TNFs. Associations of radiographic progression (ΔTSS) per year with the adjusted MBDA score, seropositivity, and clinical measures were evaluated using linear and logistic regression. The adjusted MBDA score was (1) validated in Leiden and SWEFOT, (2) compared with other measures in all four cohorts, and (3) used to generate curves for predicting risk of radiographic progression.ResultsUnivariable and bivariable analyses validated the adjusted MBDA score and found it to be the strongest, independent predicator of radiographic progression (ΔTSS > 5) compared with seropositivity (rheumatoid factor and/or anti-CCP), baseline TSS, DAS28-CRP, CRP SJC, or CDAI. Neither DAS28-CRP, CDAI, SJC, nor CRP added significant information to the adjusted MBDA score as a predictor, and the frequency of radiographic progression agreed with the adjusted MBDA score when it was discordant with these measures. The rate of progression (ΔTSS > 5) increased from < 2% in the low (1–29) adjusted MBDA category to 16% in the high (45–100) category. A modeled risk curve indicated that risk increased continuously, exceeding 40% for the highest adjusted MBDA scores.ConclusionThe adjusted MBDA score was validated as an RA disease activity measure that is prognostic for radiographic progression. The adjusted MBDA score was a stronger predictor of radiographic progression than conventional risk factors, including seropositivity, and its prognostic ability was not significantly improved by the addition of DAS28-CRP, CRP, SJC, or CDAI.

One-hour post-load glucose improves the prediction of cardiovascular events in the OPERA study

Background To estimate the ability of fasting, 1-h, and 2-h post-load glucose to predict cardiovascular outcomes. Methods We examined a population-based study consisting of 977 middle-aged subjects who underwent an oral glucose tolerance test with glucose values measured at 0, 60, and 120 min. Participants were followed up to 24 years, and cardiovascular outcomes were collected from national registers. Predictive abilities of fasting, 1-h, and 2-h glucose were evaluated alone and in the prediction models with traditional cardiovascular risk factors using Cox proportional hazard models, the likelihood-ratio test, Harrell's concordance index and integrated discrimination improvement. Results Cardiovascular endpoint occurred in 222 (22.7%) participants during a median follow-up of 19.8 years. In the prognostic models, 1-h glucose (HR 1.67, 95%CI 1.10–2.53), but not fasting or 2-h glucose, predicted cardiovascular events statistically significantly. In addition, when adding glucose parameters into the model including traditional cardiovascular risk factors, only 1-h glucose improved the predictive ability (LR-test p=.046). Finally, 1-h glucose found slightly over 50% more cardiovascular endpoints that were not recognized by fasting or 2-h glucose levels. Conclusions Our findings support the earlier ones suggesting that 1-h glucose would be a better long-term predictor of cardiovascular morbidity and mortality than fasting or 2-h glucose. KEY MESSAGES In addition to conventional CV risk factors,1-h but not fasting or 2-h post-load glucoses seems to be an independent predictor of cardiovascular events and seems to improve the predictive ability of the traditional cardiovascular risk model. Elevated 1-hpost-load glucose finds a large number (slightly over 50%)of cardiovascular endpoints that were not recognized by fasting or 2-h post-load glucose levels. One-hour glucose seems to be a better long-term predictor of cardiovascular morbidity and mortality than fasting or 2-h post-load glucose.

Operatic Forays into Translation Studies: Translation, Adaptation and Rossini’s Otello

This article examines the ties between translation studies and opera studies through the lens of Rossini’s opera, Otello. The first part of the paper demonstrates how critics have the tendency to measure the opera’s success based on its correspondence to Shakespeare’s play. Notably, the rhetoric that they use closely resembles certain types of source-text oriented discourse that recur in translation studies, and which have often proved to be problematic. The second part of this paper sets out to demonstrate that this approach to the opera is misleading as it presupposes a direct connection between the opera and play, which does not exist. After all, the librettist of the opera, Francesco Berio di Salsa, had no knowledge of English and was therefore obliged to work with a French adaptation, an Italian adaptation and possibly an Italian translation. The translator and adapters were themselves unfamiliar with English and also had to rely on other translations and adaptations, thereby creating a complex literary web. Although the word “translation” has often been used metaphorically to describe the relationship between Shakespeare’s play and Rossini’s opera, the concrete ways in which translation has intervened have rarely been analyzed. This paper therefore calls for a closer examination of the role of translation in order to elucidate the relationship between an opera and its literary sources, arguing for a descriptive rather than prescriptive approach in order to take into account the specificities of genres and the particular aesthetic context in which each text was elaborated. Ultimately, this paper seeks to illustrate how looking at the role of translation in the creation of opera libretti can at once contribute to the interdisciplinary field of opera and translation, as well as enrich both fields of study.

Establishment of “Drama” Orientation: Transition of the Research Paradigm of Chinese Dramas in the 1920s and 1930s by Yifan Zhang

Reviewed by: Establishment of “Drama” Orientation: Transition of the Research Paradigm of Chinese Dramas in the 1920s and 1930s by Yifan Zhang Weiyu Li ESTABLISHMENT OF “DRAMA” ORIENTATION: TRANSITION OF THE RESEARCH PARADIGM OF CHINESE DRAMAS IN THE 1920s AND 1930s. By Yifan Zhang. Milton: Routledge, 2019. 232pp. $128.00. Through his compelling use of drama as a lens, Yifan Zhang’s Establishment of “Drama” Orientation: Transition of the Research Paradigm of Chinese Dramas in the 1920s and 1930s (hereafter Establishment) captures the cultural collision and exchange between China and the West as well as Chinese intellectuals’ visions of national essence and identity during one of the most significant periods in modern Chinese history: the 1920s and 1930s. Framed within this pivotal period, Zhang argues that the procedure of exploring the new concept of “national drama” and practicing it went hand-in-hand with China’s project of intense nation building. Moreover, he examines how this project necessarily promoted a certain understanding of culture to the Chinese in the modern context, and the cultural and psychological roots of Chinese pursuit of national drama, as a deeply inherent part of China’s nation building. To provide an in-depth reading of the evolution and development of the academic history of Chinese national dramas, Zhang further narrows his focus to the span of years between 1925 and 1937. Standing at this transitional moment between the iconic May Fourth period (1915–1925) and the eight-year War of Resistance against Japan (1937–1945), Zhang takes the National Drama movement in 1925 as a starting point from which to tackle three questions: what is “national drama”? What is the interaction between Chinese dramatic art and criticism during the journey of exploring and defining Chinese national drama? And how does this complex interaction of writers, performers, critics, and audiences promote the development of various dramatic theories, criticism, and performance arts? Contextualizing these questions with a historical approach from a cross-cultural perspective, Zhang successfully answers the questions by tracing not [End Page 587] only the emergence and influence of the Chinese National Drama Movement but also the shift of Chinese national drama studies from literature orientation to drama orientation. Furthermore, instead of mainly focusing on Chinese intellectuals’ debate about “old” and “new” cultures or the failure of the Chinese National Drama Movement during this critical time, however, the author gives more importance to how this movement promoted the construction and development of modern performance art theories and the discipline of opera and drama studies in early modern China. This book provides valuable, original, and inspiring sources on the Chinese pursuit of national drama, culture, as well as identity. It is a must-read work for educator and students in Chinese theatre studies, modern Chinese studies, and (post)colonial studies. As Yifan Zhang states in his Introduction, Chinese intellectuals’ views of what “national drama” would be and how to achieve it were not homogeneous. In Chapter 1, Zhang systematically traces the emergence and uses of the word “drama” in Chinese, and points out that this word includes various performance forms: it could either refer to xiqu, huaju, or wenmingxi. From this very ambiguity contained in the word “drama,” then Zhang shows the reader the complex cultural tensions and exchanges between China and West, old and new, traditionalism and modernism in the field of drama, and provides a sounder basis for understanding how these interactions promoted and impacted the National Drama Movement in 1925. With this promising premise, in Chapter 2, Zhang delivers an insightful view of the evolution and historical role of “national drama” from 1925 to 1937. He introduces the story of the “National Drama Movement” initiated by Yu Shangyuan in 1925 and the academic evaluation of this movement, and analyzes how the term “national drama” that was newly created in “National Drama Movement” gradually evolved to be the representation of Chinese traditional opera. Furthermore, he argues that the discovery of “national drama” provided the Chinese with both theoretical and body languages to not only discuss the notions of the national essence and cultural heritage that first entered Chinese discourse in the late Qing period but also to rehearse and stage national identity in the...

Дуалізм у музично-художньому втіленні образу Азучени в опері «Трубадур» Дж. Верді: технічні рекомендації

The aim of the article is to consider the musical embodiment of the image of the Mother in the dramatic basis of the work, the characteristics of the image, and how the dramatic image of the work depends on the stage image, techniques in performing the opera part, namely analysis on the example Verdi in the performing context. Also, the aim of the article is consideration of the possibilities of voice and techniques for the formation of the image of the Mother in the European opera music of the XIX–XX centuries, the identification of typical features of parallel dramatic lines. The methodology of the article is a combination of the principles of historical-cultural and typological methods, as well as stylistic analysis of performance. The scientific novelty is as follows: in the opinion of the author of the article, in modern studies of opera, two parallel dramatic lines in the image of Azuchena’s opera “Troubadour” by Giuseppe Verdi are not sufficiently studied. In a play, in turn, one dramatic line dominates over another or they act equally, uniting. This is a great challenge for the performer. This article examines the dualism in the musical-artistic embodiment, that is, the unification in one role of the images of Mother and Daughter who coexist in one heroine. Therefore, the performance coverage of this topic significantly complements the musicological theory of opera and its performance aspect. Conclusions. This article reveals the musical and artistic embodiment of dualism in the image of Azuchena in Giuseppe Verdi’s opera The Troubadour; extensive experience of the author’s work on the stage image, vocal difficulties that arise in an inexperienced performer, technical recommendations for party preparation, the ability to master the psychological load are revealed and systematized; the author’s goal was achieved as a singer to pass on his experience to the next generation of performers of the Azuchena part in Giuseppe Verdi’s opera The Troubadour. The practical value of the article is determined by the possibility of using its materials in the class of solo singing, as well as for courses in theory and history of performance in higher and secondary music school. The article is written on the example of the author’s own performance of Azuchena’s party.

Collecting Theater in Republican Beijing: Research Methods and the Birth of Chinese Opera Studies in Early Twentieth-Century China

Collecting Theater in Republican Beijing: Research Methods and the Birth of Chinese Opera Studies in Early Twentieth-Century China

1537P Phase I/II study with CXCL12 inhibitor NOX-A12 and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer

NOX-A12 is a CXCL12 inhibitor that prevents activation of receptors CXCR4 and CXCR7 and blocks formation of CXCL12 concentration gradients. The Opera study is a phase I/II study to investigate pharmacodynamics of NOX-A12 monotherapy and safety and efficacy of a combination with pembrolizumab in metastatic MSS colorectal (CRC) and pancreatic (PaC) cancer where PD-1 inhibition alone has no clinical benefit. Patients received NOX-A12 twice weekly for 2 weeks. Biopsies were taken from liver metastases before and after treatment to analyze immune cells and cytokines. Subsequently, patients received repeated 21-day cycles of NOX-A12 and pembrolizumab. 11 patients had CRC and 9 PaC. All patients were heavily pretreated with 5 (CRC) and 3 mean lines (PaC) of prior treatment. Best response to last prior treatment was progressive disease in 95% of cases. The AE profile was comparable with the pembrolizumab profile and typical for the underlying diseases. 2 weeks of NOX-A12 monotherapy induced changes in the tumor microenvironment: an upregulated cassette of Th1 cytokines in approx. 50% of patients, being associated with better clinical stabilization. Biopsy analysis before and after NOX-A12 monotherapy showed agglomeration of T cells and migration of T cells towards cancer cells in patients where NOX-A12 induced a Th1-type response. These trends suggest that CXCL12 inhibition increased effector immune cell infiltration of the tumor, resulting in a more effective immune response. 25% of patients achieved stable disease (SD) and long term disease control. Remarkably, 7 patients showed prolonged time on treatment vs. prior therapy. Median PFS was 1.87 months, OS was 42% at 6 and 22% at 12 months. Agglomeration of T cells within tumors was seen in ∼half of the patients where NOX-A12 had induced a Th1-type cytokine response. This was accompanied by reduced distances between T and cancer cells, i.e. more engaged T cells. Increased infiltration of effector immune cells into tumor was associated with SD in 25% of patients and prolonged time on treatment vs. prior therapy for 35% of pts. Safety profile of the combination was consistent with that of pembrolizumab in advanced cancer patients.

Abstract CT117: Phase 1/2 study with CXCL12 inhibitor NOX-A12 and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer

Abstract Background: NOX-A12 is an inhibitor of the chemokine CXCL12 which prevents engagement with its receptors CXCR4 and CXCR7 and blocks the formation of chemotactic CXCL12 concentration gradients in tissue. The Opera study (NCT03168139) is a Phase 1/2 study to evaluate pharmacodynamic effects and safety of monotherapy with NOX-A12 as well as safety and efficacy of a combination with pembrolizumab in metastatic microsatellite-stable colorectal and pancreatic cancer where PD-1 inhibition alone has not shown clinical benefit. Methods: Patients received 300 mg NOX-A12 twice weekly during a 2-week monotherapy phase. Biopsies were taken from liver metastases before and after NOX-A12 monotherapy for analysis of immune cell infiltration and cytokine signature. In a combination phase, patients received repeated 21-day cycles of 300 mg NOX-A12 and 200 mg pembrolizumab until progression or intolerable toxicity. Results: 11 of the patients had CRC and 9 PaC. All patients were heavily pretreated with 5 (colorectal cancer) and 3 median lines (pancreatic cancer) of prior treatment. Best responses to last prior treatment was progressive disease for 95% of patients. The AE profile was comparable with the pembrolizumab profile or typical for the underlying diseases. Two weeks of NOX-A12 monotherapy induced Th1 cytokines (IFNγ, IL-2, IL-16) in approx. half of the patients. Comparison of tumor biopsies from before and after NOX-A12 monotherapy shows trends towards (i) agglomeration of T cells and (ii) migration of T cells towards cancer cells in the patient sub-group where NOX-A12 induced a Th1-type cytokine response. These trends are consistent with preclinical data (Feig 2013, PNAS 110:20212; Zboralski 2017, Cancer Immunol Res 5:950), suggesting that neutralization of CXCL12 signaling - either through one or both receptors - increased infiltration of effector immune cells into tumor tissue and resulted in a more effective immune response. Although there were no objective responses, 25% of patients achieved stable disease; 7 patients showed prolonged time on treatment vs. the prior line of therapy. Median progression-free survival was 1.87 months, overall survival was 42% at 6 months and 22% at 12 months. Conclusions: A trend towards agglomeration of T cells within tumors was observed in about half of the patients where NOX-A12 had induced a Th1-type cytokine response. This agglomeration was accompanied by reduced distances between T cells and cancer cells, suggesting increased infiltration of effector immune cells into tumor tissue. Treatment with NOX-A12 plus pembrolizumab in the combination therapy part of the study resulted in stable disease in 25% of patients, and prolonged time on treatment vs. prior therapy for 35% of patients. The safety profile of the combination therapy was consistent with that of pembrolizumab in advanced cancer patients. Citation Format: Niels Halama, Anja Williams, Ulrike Prüfer, Anna Frömming, Diana Beyer, Dirk Eulberg, Jarl Ulf Jungnelius, Aram Mangasarian. Phase 1/2 study with CXCL12 inhibitor NOX-A12 and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT117.

Five years of ocrelizumab in relapsing multiple sclerosis: OPERA studies open-label extension.

ObjectiveTo assess over 3 years of follow-up the effects of maintaining or switching to ocrelizumab (OCR) therapy on clinical and MRI outcomes and safety measures in the open-label extension (OLE) phase of the pooled OPERA: I/II studies in relapsing multiple sclerosis.MethodsAfter 2 years of double-blind, controlled treatment, patients continued OCR (600 mg infusions every 24 weeks) or switched from interferon (IFN)-β-1a (44 μg 3 times weekly) to OCR when entering the OLE phase (3 years). Adjusted annualized relapse rate, time to onset of 24-week confirmed disability progression (CDP)/improvement (CDP), brain MRI activity (gadolinium-enhanced and new/enlarging T2 lesions), and percentage brain volume change were analyzed.ResultsOf patients entering the OLE phase, 88.6% completed year 5. The cumulative proportion with 24-week CDP was lower in patients who initiated OCR earlier vs patients initially receiving IFN-β-1a (16.1% vs 21.3% at year 5; p = 0.014). Patients continuing OCR maintained and those switching from IFN-β-1a to OCR attained near complete and sustained suppression of new brain MRI lesion activity from years 3–5. Over the OLE phase, patients continuing OCR exhibited less whole brain volume loss from double-blind study baseline vs those switching from IFN-β-1a (−1.87% vs −2.15% at year 5; p < 0.01). Adverse events were consistent with past reports and no new safety signals emerged with prolonged treatment.ConclusionCompared with patients switching from IFN-β-1a, earlier and continuous OCR treatment up to 5 years provided sustained benefit on clinical and MRI measures of disease progression.Classification of evidenceThis study provides Class III evidence that earlier and continuous treatment with OCR provided sustained benefit on clinical and MRI outcomes of disease activity and progression compared with patients switching from IFN-β-1a. The study is rated Class III because of the initial treatment randomization disclosure that occurred after inclusion in OLE.Clinical trial identifiersNCT01247324/NCT01412333.

Monoclonal antibodies in the treatment of multiple sclerosis: from clinical research to practical application

Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating and neurodegenerative disease with a multifactorial etiology of development. MS in most cases has a wave-like course (periods of exacerbations and remissions), over time, the disease becomes progressive, which worsens the quality of life of patients. The drugs disease-modifying therapies (DMT) has been actively used in clinical practice for more than 30 years to prevent exacerbations and progression of MS. In patients with MS, in which the disease occurs with frequent exacerbations and signs of radiological activity of the demyelinating process, according to magnetic resonance imaging (MRI) of the brain and spinal cord, it is recommended to use monoclonal antibody preparations. The only drug registered for the treatment of primary progressive MS is ocrelizumab. In addition, ocrelizumab is indicated for patients with remitting and secondary progressive MS. Ocrelizumab is a humanized monoclonal antibody that selectively depletes a population of CD20+ B cells. The article presents data from clinical studies of OPERA I and OPERA II and describes a clinical case from the practice of a neurologist. Depletion of the B cell population is achieved by several mechanisms, including antibody-dependent cell-mediated phagocytosis, antibody-dependent T cell-mediated cytotoxicity, complement-dependent cytotoxicity, and apoptosis induction. The issues of efficacy and safety of ocrelizumab therapy in patients with MS are considered.

Post-Modern Reception of the Idea of Two People in the Tan Dun’s Opera “Marco Polo”

Relevance of the study. Contemporary operas by Chinese composers are of undoubted interest to modern musicology. Tan Dun's creative experiments are extremely interesting. His operas demonstrate the search of the contemporary composer whose interests lie at the crossroads of national oriental and academic opera traditions. Thus, in the opera “Marco Polo” the concept of dichotomy and multiculturalism receives the status of the main ideas. The study of this aspect of opera is an urgent and prerogative task in the process of understanding the operatic experience of Chinese composers.Main objective of the study is to identify the peculiarities of reading the concept of the two worlds in the opera “Marco Polo” through the prism of the postmodern search of Tan Dun.Methodology. To achieve this goal, the following scientific methods were used: historiographical (studying stages of development of Chinese opera), the method of stylistic attribution (determining the stylistic components of opera and creative constants of Tan Dun’s style), structuralfunctional method (determining the peculiarities of opera) and semantic analysis (determining the semantic layers of the work associated with the idea of the two worlds).The main results / findings and conclusions. It was found that the idea of the two worlds of “Marco Polo's” opera was generated by the aesthetics of postmodernism, as a result of which the work became a cross-cultural art project that combined several languages, cultures and periods of time. The symbolism of the plot, which is nourished by Eastern and Western aesthetic and philosophical ideas, combining in the concept of two worlds, is determined. It is noted that the composer managed to preserve the cultural differences of both worlds. The Asian world is presented in a generalized way – in the form of stylizations, which are based on the fricative, rhythmic, instrumental and performance features of oriental music within the traditions of neo-orientalism. Western music is more specific – through the prism of compositional styles in a number of quotations and allusions, as well as in the involvement of avant-garde compositional techniques. Based on this, a conclusion was made about the dominance of Western tendencies in general and the traditions of postmodernism in particular in the world of “Marco Polo”, to which elements of the Asian musical style are subordinated.A detailed study of Tan Dun's opera expands the understanding of contemporary Chinese opera, contributes to the deepening of knowledge on the development of the opera genre and allows you to navigate within the eclectic space of postmodern art.