Academic literature on the topic 'Tixan LLC'

PowerPC and high-performance computers (HPC) are important resources for computing in the ATLAS experiment. The future LHC data processing will require more resources than Grid computing, currently using approximately 100,000 cores at well over 100 sites, can provide. Supercomputers are extremely powerful as they utilize hundreds of thousands of CPUs joined together. However, their architectures have different instruction sets. ATLAS binary software distributions for x86 chipsets do not fit these architectures, as emulation of these chipsets results in huge performance loss. This paper describes the methodology of ATLAS software installation from source code on supercomputers. The installation procedure includes downloading the ATLAS simulation release code with 0.7 million C++ and Python lines as well as the source code of more than 50 external packages, such as ROOT and Geant4, followed by compilation, and rigorous unit and integration testing. The presentation reports the application of this procedure at Titan HPC and Summit PowerPC at Oak Ridge Computing Facility (OLCF).

At 0440 on July 14, 1953, the 468-foot long C3 Cargo/Oil Carrier SS Jacob Luckenbach was struck by the SS Hawaiian Pilot about 31 km (17 miles) west of the Golden Gate Bridge, San Francisco, CA. The Luckenbach sank with no loss of life, but sustained massive structural damage from the collision, which caused the sinking. At the time of her collision and sinking she was in route to Korea with a full cargo of jeeps, trucks, and railroad equipment for the Korean War effort. It is estimated that her bunkers were topped off for the trip with heavy bunker C oil.In early 2002, the Luckenbach was identified as the source of "mystery" oil spills along the California coast. In May 2002, Titan Maritime LLC, with engineers from PCCI Inc., was contracted by the U.S. Coast Guard, Pacific Area Command, San Francisco, to conduct a vessel assessment and remove available oil. Global Diving & Salvage, Seattle, provided saturation diving services and Crowley Maritime provided the primary work barge and tug services.Problems encountered included extended cold-water saturation diving at depths to 55 m, strong reversing currents, extremely adverse weather, and poor sub-sea visibility. The heavy residual oils in the deep tanks and double bottoms also proved to be a pumping challenge since some tanks contained oil that was far more viscous than normal number 6 fuel oil (Ingersoll-Dresser, 1998).This paper describes the approach to the oil recovery from this wreck, as well as expanding upon more recent and ongoing developments in the field of emergency ship and sunken vessel viscous oil off-loading methodologies.

The article presents experimental data on explosive compaction of chromium carbide (Cr3C2) powder mixtures with metals (Ti, Ni, Cu) provided with theoretical explanations. These data were used as a basis for stating science-based principles of composition selection and technology development to produce antifriction wear-resistant chromium carbide hard alloys and coatings by explosion. Explosive compaction of powder mixtures was carried out according to a scheme using a normally incident plane detonation wave in a wide range of loading parameters (powder heating temperature in shock waves varied from 200 to1000 °Cand maximum shock compression pressure varied from 4 to 16 GPa during experiments). Phase transformation analysis was carried out by the numerical thermodynamic modeling of phase equilibrium using the Thermo-Calc software. Microstructure, chemical and phase compositions were studied using optical («Axiovert 40МАТ» by CarlZeiss,Germany), scanning («Versa 3D» and «Quanta 3D FEG» byFEI,USA), transmission («BS 540» byTesla,Czech Republic, «Titan 80-300» and «Tecnai G2 20F» byFEI,USA) electron microscopes and «Solver Pro» atomic force microscope (LLC «NT-MDT», Zelenograd). Temperature stability and oxidation resistance at elevated temperatures of the materials obtained by explosion was studied using thermogravimetric analysis (TGA) using the «STA 449 F3 Jupiter» instrument (NETZSCH, Germany) in the synthetic air environment when heated to1500 °C. Tribological tests were carried out on the MI-1M friction machine (MEZIMiV,Moscow) according to the pin-on-ring scheme with plunging in distilled water environment. The mechanisms of consolidation and formation of strong boundaries between powder material particles during explosive compaction are described. It is shown that hard alloys of chromium carbide with titanium bond obtained by explosion retain their phase compositions without any changes and resist to oxidation up to600 °C, and also have significantly better anti-friction properties and wear resistance than the SGP-0,5 and KHN-20 materials used in water-lubricated friction couples until the present time.

The unprecedented computing resource needs of the ATLAS experiment at LHC have motivated the Collaboration to become a leader in exploiting High Performance Computers (HPCs). To meet the requirements of HPCs, the PanDA system has been equipped with two new components; Pilot 2 and Harvester, that were designed with HPCs in mind. While Harvester is a resource-facing service which provides resource provisioning and workload shaping, Pilot 2 is responsible for payload execution on the resource. The presentation focuses on Pilot 2, which is a complete rewrite of the original PanDA Pilot used by ATLAS and other experiments for well over a decade. Pilot 2 has a flexible and adaptive design that allows for plugins to be defined with streamlined workflows. In particular, it has plugins for specific hardware infrastructures (HPC/GPU clusters) as well as for dedicated workflows defined by the needs of an experiment. Examples of dedicated HPC workflows are discussed in which the Pilot either uses an MPI application for processing fine-grained event level service under the control of the Harvester service or acts like an MPI application itself and runs a set of job in an assemble. In addition to describing the technical details of these workflows, results are shown from its deployment on Titan (OLCF) and other HPCs in ATLAS.

124 Background: Apalutamide (APA) is approved to treat patients with non-metastatic castration-resistant prostate cancer (nmCRPC) or metastatic castration-sensitive prostate cancer (mCSPC) in the United States (US) but low enrollment of Black patients in clinical trials has led to limited clinical data about APA for this population. This study describes prostate-specific antigen (PSA) responses among Black and non-Black patients with nmCRPC or mCSPC treated with APA in a real-world community urology setting. Methods: Clinical data from 2/2018 to 3/2021 collected at 69 US urology practices were used to evaluate nmCRPC or mCSPC patients who received ≥1 APA prescription fill (index date). Baseline PSA was reported based with the most recent baseline PSA value and PSA doubling time (PSADT) in months (mo) was calculated in patients with at least 2 PSA tests before APA initiation. PSA response defined as the proportion of patients achieving either a reduction of 50% (PSA50) or 90% (PSA90) from baseline and was evaluated in patients with a PSA test result 8 weeks or later after initiating APA. Among patients with a response, the time from the index date to the response was also evaluated. Study results for Black and non-Black cohorts were summarized separately. Results: Data from 289 nmCRPC (19% Black) and 237 mCSPC (19% Black) patients were identified. Median baseline PSA, median baseline PSADT and post-index PSA responses are shown in Table. A PSA50 response was attained by numerically similar proportions of Black and non-Black patients with nmCRPC or mCSPC. A PSA90 response was observed in a numerically higher proportion of Black than non-Black nmCRPC patients. Median time to PSA50 and PSA90 was also similar between groups. Conclusions: This real-world study of nmCRPC and mCSPC patients demonstrates that PSA50 and PSA90 responses are achieved by high proportions of both Black and non-Black patients. Moreover, the PSA50 and PSA90 responses observed in this study are highly consistent with those observed in APA’s Phase 3 registrational trials for nmCRPC (SPARTAN)1 and for mCSPC (TITAN)2. References: 1Smith MR, et al. N Engl J Med. 2018;378:1408-1418. 2Chi KN, et al. N Engl J Med. 2019;381:13-24. Funding Source: Janssen Scientific Affairs, LLC.[Table: see text]

Viljelijäväestön tulotasoa ja sen muutoksia tutkittaessa joudutaan usein tarkastelemaan myösharjoitetun maatalouden merkitystä viljelijän kokonaistulonmuodostuksessa. Suomalaisissa tarkasteluissamaatilat on useimmiten jaettu neljään ryhmään sen perusteella, mikä osuus viljelijäpuolisoidentuloista tulee maataloudesta. Suora, tulo-osuuteen perustuva, ryhmittely kuitenkin huomioi herkästiväliaikaisten tulonvaihteluiden (esim. katovuosi, eläintaudit) vaikutuksen luokittelussa. Luokittelunsatunnainen vaeltelu aiheuttaa ylimääräistä virhettä aikasarjatarkasteluihin. Vakaamman luokittelijanmuodostamiseksi on tulotasotutkimuksen yhteydessä tutkittu mahdollisuutta hyödyntää tulotietojenlisäksi myös työpanoksen käyttötietoja maatalouden päätoimisuusasteen määrittelyssä.Luokitus muodostettiin vuoden 2003 verolomakkeilta saatavien viljelijöiden tulotietojen ja samanavuonna MMM/TIKE:n keräämien Maatalouden rakennetutkimuksen työvoimankäyttötietojenperusteella. Tulo- ja työnkäyttötietojen pohjalta tilat jaettiin ryhmittelyanalyysillä samankaltaistentilojen ryhmiin. Vastaavan tyyppistä analyysiä on sovellettu tekijöiden aiemmassa tutkimuksessa vuoden2000 tietoihin. Aiempaan tutkimukseen verrattuna tässä tutkimuksessa käytettiin yksinkertaisempaaanalyysimenettelyä ja suppeampaa aineistoa. Aiemmassa tutkimuksessa vuoden 2000 tiedot olikäytettävissä n. 8000 tilalta kun taas tässä vastaavat tiedot oli saatavissa vain n. 4200 tilalta lähtöaineistojenerilaisen keruutavan vuoksi.Analyysimenetelmien osalta merkittävimmät muutokset olivat tarkastelussa käytettävien muuttujienmäärän huomattava vähentäminen (2000 75kpl – 2003 3 kpl) sekä aineiston analysoiminen suoraanklusterianalyysillä. Analyysissä käytettiin muuttujina maataloustulojen osuutta kokonaistuloistaja viljelijäpuolisoiden työajankäyttöä TIKE:n kyselyn 7-portaisen luokituksen mukaan. Vuoden 2000tietojen analyysissä oli käytetty suurempaa joukkoa yksityiskohtaisempia tietoja maataloudesta, tulosta,menoista ja omaisuudesta. Tätä muuttujajoukkoa oli ”tiivistetty” faktorianalyysillä ennen klusterianalyysiä.Klusteroinnin perusteella aineisto jaettiin kuuteen ryhmään, jotka edustavat erityyppisiä maatiloja.Tulosten mukaan viljelijäpuolisoiden tiloista 35 % voidaan katsoa olevan sekä tulo että työajankäytönsuhteen päätoimisia kotieläintiloja. Näillä tiloilla maatalouden osuus kokonaistuloista on n. 86% ja molempien puolisoiden työaika käytetään miltei kokonaan maataloudessa. Tiloista 19 %:lla hankitaankeskimäärin 55 % kokonaistuloista palkkatyöstä ja työajan perusteella molemmat viljelijäpuolisoistaovat ainakin sivutoimisesti tilan ulkopuolella töissä. Loput 46 % tiloista jakautui neljään suunnilleensamankokoiseen ryhmään, joiden voidaan katsoa sijoittuvan maatalouden päätoimisuuden asteenperusteella em. ääriryhmien väliin. Täten voidaan todeta aiempaan verrattuna huomattavasti selkeämmälläanalysointitavalla saavutettavan asetettujen luokitustavoitteiden mukaisia tuloksia.

Background:Patients with psoriatic arthritis (PsA) present with heterogeneous clinical phenotypes, which includes different clinical manifestations such as peripheral arthritis, axial disease, dactylitis, enthesitis, and skin and nail psoriasis. Many drugs for treatment of PsA are available for individualised treatment strategies but robust evidence is available for peripheral arthritis only as primary endpoint of RCTs.Objectives:To evaluate perception of German physicians on the value of current PsA treatments on different clinical PsA manifestations.Methods:In a face-to-face meeting, 8 German physicians (dermatology, rheumatology), specialised in PsA research/patient care, proposed initial scores for the effect size of current PsA drugs on different PsA manifestations based on knowledge of study data and personal experience in use of the drugs. The ability to achieve a consensus of the proposed efficacy scores was explored by applying an online survey among a cohort of PsA experienced physicians. Finally, a second online survey evaluated how a larger group of physicians personally estimate the drug effect sizes on different PsA manifestations.Results:Table 1 summarises the efficacy scores proposed by the initial expert group. In the first online survey 25 treating physicians were invited to participate, 14 (56%) of whom completed the survey. An agreement rate of over 65% of the participants was archived for 49 (68%) of the 72 proposed efficacy scores (Table 1). The consensus was especially high for the group of biological disease-modifying antirheumatic drugs (bDMARDs), except for etanercept and abatacept. However, the second survey (16 (39%) participants out of 41 invited physicians) revealed that the experience with the treatment using abatacept was low (4 / 16 (25%)) or non-existing (3 /16 (18.8%)) and several manifestations could not be estimated (Figure 1). Distribution of answers were broad for etanercept in general and for particular drug-manifestation combinations (e.g. effect of ustekinumab on axial disease).Table 1.Efficacy scores proposed by a PsA expert group and consensus achieved by an online survey among PsA treating physicians Efficacy scores for different drugs and manifestations range from 0 (no effect) to 5 (maximal effect). Green fields indicate, that at least 65% of the survey participants agreed on the proposed efficacy score.Peripheral arthritisAxial diseaseEnthesitisDactylitisSkin diseaseNail diseaseMethotrexat2.50012.51.5Sulfasalazin100000Leflunomid2.500111Apremilast3132.533Etanercept4443.533.5Infliximab444444Adalimumab444444.5Golimumab444433Certolizumab pegol444444Ustekinumab3.52.54.534.54Secukinumab444454.5Abatacept3.50001.50Figure 1.Results from an online survey among physicians querying their perception of efficacies of PsA drugs on different manifestations. Therapeutic effectiveness is estimated by the participants on a scale from 0 (no effect) to 5 (maximal effectiveness); NA = no answer. The size of the dots relates to the number of answers given. Red stars indicate the scores proposed by the initial expert group.Conclusion:Many treatments are available to be used in PsA. The usage of treatment classes seems to depend on experience level and mode of action. Higher agreement on efficacy in specific diseases manifestation was achieved in the class of biologics whereas the opinion on efficacy of csDMARDs in general is divergent. Strategies are needed to guide physicians with lower level of experience in the use of specific drugs to achieve an optimised patient care level using personalized treatment strategies.Disclosure of Interests:Timm Oberwahrenbrock Grant/research support from: BMS, Hannah Tian: None declared, Diamant Thaçi Grant/research support from: Janssen Research & Development, LLC, Klaus Krueger Consultant of: Celgene, Jürgen Wollenhaupt Consultant of: Celgene, Michaela Köhm Grant/research support from: Pfizer, Janssen, BMS, LEO, Consultant of: BMS, Pfizer, Speakers bureau: Pfizer, BMS, Janssen, Novartis, Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Lilly and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai

Предложена методика модифицирования InP в парах серы, методом локального рентгеноспектрального микроанализа подтверждено её наличие на поверхности. Дляплёнок нанометрового диапазона толщины (до 50 нм), выращенных термическим оксидированием InP с предварительно обработанной в парах серы поверхностью, методом Оже-электронной спектроскопии установлено послойное распределение компонентов. По данным атомно-силовой микроскопии модифицирование InP серой приводит к формированию поверхности с зернистой структурой, более упорядоченной по сравнению с эталоном (собственное термооксидирование фосфида индия). Несмотря на то, что в результирующих плёнках сера не обнаружена, они обладают полупроводниковыми свойствами, тогда как для собственных оксидных слоёв на InP характерна омическая проводимость REFERENCES Markov V. F., Mukhamedzyanov Kh. N., Maskaeva L. N. Materialy sovremennoj jelektroniki [Materials of modern electronics]. Ekaterinburg, Publishing Ural. un-one, 2014, 272 p. (in Russ.) 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Abstract Background: Zanubrutinib is a selective next-generation Bruton tyrosine kinase (BTK) inhibitor designed to have high specificity for BTK and minimize off-target effects (J Med Chem 2019;62:7923-40). Data from several phase 2 CLL trials assessing BCL-2 and BTK inhibitor combination treatment suggested that undetectable minimal residual disease (uMRD)-driven fixed-duration combination treatment was tolerable and enabled durable responses after treatment discontinuation (JAMA Oncol 2021;1649.; EHA 2021 S147). However, a limited number of patients with the high-risk feature, deletion of chromosome 17p13.1 [del(17p)], have been included in these studies. Preliminary data from Arm C of the SEQUOIA trial suggested that zanubrutinib monotherapy was active (18-mo progression-free survival: 90.6%) and well-tolerated in CLL/SLL patients with del(17p) (ASH 2020 1306). Here, we present early results for patients with TN del(17p) CLL/SLL receiving zanubrutinib + venetoclax in Arm D of the SEQUOIA trial (NCT03336333). Methods: SEQUOIA is an open-label, global, multicenter, phase 3 study that includes a nonrandomized cohort (Arm D) of patients with TN del(17p) CLL/SLL (Blood 2020;136 [supplement 1]:24-5). Patients in Arm D were treated with zanubrutinib (160 mg twice daily) for 3 mos followed by zanubrutinib (same dosing) + venetoclax (ramp-up cycle followed by 400 mg once daily) combination treatment for 12-24 cycles until progressive disease (PD), unacceptable toxicity, or achievement of uMRD at <10 -4 sensitivity by flow cytometry (whichever occurred first). Adult patients with CLL/SLL who met International Workshop on CLL (iwCLL) criteria for treatment (Blood 2008;111:5446-56) were eligible if they had central verification of del(17p) by fluorescence in situ hybridization with >7% aberrant nuclei present. Initial safety and tolerability of zanubrutinib + venetoclax was assessed, including the risk of tumor lysis syndrome (TLS) both at baseline and prior to initiation of venetoclax. Responses for CLL and SLL were investigator-assessed per modified iwCLL criteria (Blood 2008;111:5446-56; J Clin Oncol 2012;30:2820-2) and Lugano criteria (J Clin Oncol 2014;32:3059-68), respectively. Bone marrow exams to confirm a suspected complete response (CR) or CR with incomplete hematological recovery were required starting at the end of Cycle 9. Results: As of 1 JUN 2021 (data cutoff), 35 of approximately 80 planned patients with centrally confirmed del(17p) were enrolled. Median follow-up was 9.7 mos. In the safety analysis population (n=35), 94.3% had CLL and high-risk characteristics including Binet stage C (51.5%), bulky disease ≥5 cm (42.9%), unmutated immunoglobulin heavy chain variable locus (85.3%, n=34), median del(17p) frequency of 81.5%, and elevated β 2-microglobulin (71.4%). At data cutoff, 29 patients had started combination therapy and 27 patients completed ramp-up venetoclax dosing. Thirty-two patients remained on study treatment and 3 patients ended treatment due to withdrawal of consent, PD, or adverse event (AE of lung cancer), all n=1. The patient with lung cancer had lung nodules present at screening and died due to lung adenocarcinoma. AEs and serious AEs were reported in 29 patients (82.9%) and 4 patients (11.4%), respectively. AEs reported in ≥10% of patients included diarrhea (n=5), neutropenia (n=5), fatigue (n=4), nausea (n=4), and petechiae (n=4). Thirteen patients (37.1%) had grade ≥3 AEs; most frequently neutropenia (n=4) and diarrhea (n=2). One patient with ongoing grade 2 atrial fibrillation at baseline reported grade 3 atrial fibrillation on study. To date, no AEs of TLS have been reported. At baseline, the TLS risk categories were high, medium, and low in 12 (34.3%), 22 (62.9%), and 1 (2.9%) patients, compared with 0 (0%), 21 (67.7%), and 10 (32.3%) patients, respectively, prior to initiation of venetoclax. For the 31 patients who reached the initial efficacy assessment at 3 mos after starting zanubrutinib, the overall response rate was 96.8% (30/31); one patient reported PD after having an initial partial response while on combination therapy. Conclusion: Preliminary safety data with the 9.7-mo median follow-up suggest that zanubrutinib + venetoclax was generally well tolerated in this high-risk population, with no new safety signals identified and no TLS reported. Enrollment is ongoing; updated safety, efficacy, and biomarker data will be presented. Figure 1 Figure 1. Disclosures Tedeschi: AbbVie: Honoraria, Other: Advisory Board and Travel, Accommodations, Expenses, Speakers Bureau; Janssen: Honoraria, Other: Advisory Board and Travel, Accommodations, Expenses, Speakers Bureau; BeiGene: Honoraria, Other: Advisory Board, Speakers Bureau; AstraZeneca: Honoraria, Other: Advisory Board, Speakers Bureau. Ferrant: Janssen: Other: Travel, Accommodations, Expenses; AbbVie: Honoraria, Other: Travel, Accommodations, Expenses; AstraZeneca: Honoraria. Flinn: Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Sarah Cannon Research Institute: Current Employment; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current holder of individual stocks in a privately-held company; Seattle Genetics: Research Funding. Tam: Roche: Consultancy, Honoraria; Novartis: Honoraria; Pharmacyclics: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Loxo: Consultancy; AbbVie: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria. Ghia: Acerta/AstraZeneca: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; ArQule/MSD: Consultancy, Honoraria; Celgene/Juno/BMS: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Gilead: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Sunesis: Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding. Robak: Biogen, Abbvie, Octapharma, Janssen: Honoraria, Other: Advisory board; AstraZeneca, Abbvie, Janssen, Octapharma, Gilead,Oncopeptides AB, Pharmacyclics, Pfizer, GlaxoSmithKline, Biogen: Research Funding; Medical University of Lodz: Current Employment. Brown: MEI Pharma: Consultancy; Bristol-Myers Squib/Juno/Celegene: Consultancy; Pfizer: Consultancy; Abbvie: Consultancy; Sun: Research Funding; Gilead: Research Funding; Rigel: Consultancy; Catapult: Consultancy; Eli Lilly and Company: Consultancy; Genentech/Roche: Consultancy; Novartis: Consultancy; Invectys: Other: Data Safety Monitoring Committee Service; Beigene: Consultancy; Nextcea: Consultancy; Morphosys AG: Consultancy; TG Therapeutics: Research Funding; Acerta/Astra-Zeneca: Consultancy; Janssen: Consultancy; SecuraBio: Research Funding; Loxo/Lilly: Research Funding. Ramakrishnan: BeiGene: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Other: Travel, Accommodations, Expenses. Tian: AbbVie: Ended employment in the past 24 months; BeiGene: Current Employment. Kuwahara: BeiGene: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Paik: BeiGene USA, Inc.: Current Employment, Current equity holder in publicly-traded company. Cohen: BeiGene: Current Employment, Current equity holder in publicly-traded company, Other: Travel, Accommodations, Expenses. Huang: BeiGene: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months, Other: Travel, Accommodations, Expenses; Protara Therapeutics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Hillmen: BeiGene: Honoraria; Janssen: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; AbbVie: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Pharmacyclics: Honoraria, Research Funding; Roche: Research Funding; Gilead: Research Funding; AstraZeneca: Honoraria; SOBI: Honoraria. OffLabel Disclosure: Zanubrutinib is an investigational agent and has not been approved for TN del(17p) CLL/SLL in the US

Abstract Background: Zanubrutinib (zanu) is a selective next-generation Bruton tyrosine kinase (BTK) inhibitor designed to have high specificity for BTK and minimize off-target effects (Guo, J Med Chem 2019;62:7923-40). In a phase 1/2 study, zanu demonstrated complete and sustained BTK occupancy in both peripheral blood mononuclear cells and lymph nodes and was associated with durable clinical responses in patients (pts) with CLL/SLL (Tam, Blood 2019;134:851-9). Here, we present interim results for the phase 3 SEQUOIA (BGB-3111-304; NCT03336333) trial, which evaluated the efficacy and safety of zanu vs BR in TN pts with CLL/SLL. Methods: SEQUOIA is an open-label, global phase 3 study that randomized TN pts with CLL/SLL without del(17p) to receive zanu 160 mg twice daily until progressive disease or unacceptable toxicity, or bendamustine 90 mg/m 2 on day 1 and 2 and rituximab 375 mg/m 2 in cycle 1, 500 mg/m 2 in cycles 2-6 for 6 × 28-day cycles. Adult pts with CLL/SLL who met International Workshop on CLL (iwCLL) criteria for treatment (Hallek, Blood 2008;111:5446-56) were eligible if they were either ≥65 y or unsuitable for treatment with fludarabine, cyclophosphamide and rituximab. Central verification of del(17p) status by fluorescence in situ hybridization was required. Pts were stratified by age (<65 y vs ≥65 y), Binet Stage (C vs A/B), IGHV mutational status, and geographic region. The primary endpoint was independent review committee (IRC)-assessed progression-free survival (PFS) for zanu vs BR. Secondary endpoints included PFS by investigator assessment (INV), overall response rate (ORR; by IRC and INV), overall survival (OS), and safety. Responses for CLL and SLL were assessed per modified iwCLL criteria (Hallek, Blood 2008;111:5446-56; J Clin Oncol 2012;30:2820-2) and Lugano criteria (Cheson, J Clin Oncol 2014;32:3059-68), respectively. Adverse events (AEs) were recorded until disease progression to support safety evaluation over an equivalent time period. Results: From 31 Oct 2017-22 Jul 2019, 479 pts without del(17p) were randomized to zanu (n=241) and BR (n=238). Treatment groups were well balanced for demographic and disease characteristics (zanu vs BR): median age, 70.0 y vs 70.0 y; unmutated IGHV, 53.4% (125/234) vs 52.4% (121/231); and del(11q), 17.8% vs 19.3%. At median follow-up (26.2 mo), PFS by IRC was significantly prolonged with zanu vs BR (HR 0.42, 95% CI 0.28-0.63, 1-sided and 2-sided P<0.0001; Figure); similar results were observed by INV (HR 0.42, 95% CI 0.27-0.66, 1-sided P<0.0001, 2-sided P=0.0001). Treatment benefit for zanu was observed across subgroups for age, Binet stage, bulky disease, and del(11q) status. Treatment benefit was also observed for pts with unmutated IGHV (HR 0.24, 1-sided and 2-sided P<0.0001), but not for mutated IGHV (HR 0.67, 1-sided P=0.0929). Estimated 24-mo PFS (IRC) for zanu vs BR was 85.5% (95% CI 80.1%- 89.6%) vs 69.5% (95% CI 62.4%-75.5%). ORR by IRC for zanu vs BR was 94.6% (95% CI 91.0%-97.1%) vs 85.3% (95% CI 80.1%-89.5%). Complete response rate was 6.6% with zanu and 15.1% with BR. ORR by INV for zanu vs BR was 97.5% (95% CI 94.7%-99.1%) vs 88.7% (95% CI 83.9%-92.4%) Estimated 24-mo OS for zanu vs BR was 94.3% (95% CI 90.4%-96.7%) and 94.6% (95% CI 90.6%-96.9%). The most common AEs are shown in the Table. AEs of interest occurring during the full reporting period (pooled terms, zanu vs BR) included atrial fibrillation (any grade [gr]: 3.3% vs 2.6%), bleeding (any gr/gr≥3: 45.0%/3.8% vs 11.0%/1.8%), hypertension (any gr: 14.2% vs 10.6%), infection (any gr/gr≥3: 62.1%/16.3% vs 55.9%/18.9%), and neutropenia (any gr/gr≥3: 15.8%/11.7% vs 56.8%/51.1%). Treatment discontinuation due to AEs occurred in 20 pts (8.3%) receiving zanu vs 31 pts (13.7%) receiving BR; 85.5% of pts receiving zanu remain on treatment. AEs leading to death occurred in 11 pts (4.6%) receiving zanu vs 12 pts (5.3%) receiving BR. No sudden deaths were reported. Conclusions: In this global registrational trial, zanu demonstrated statistically significant improvement in PFS compared to BR as assessed by IRC. Superiority was also observed in PFS by INV as well as ORR by both IRC and INV. Zanu was generally well tolerated, with low rates of atrial fibrillation consistent with those observed in the phase 3 ASPEN (Tam, Blood 2020;136:2038-2050) and ALPINE studies (Hillmen, EHA 2021 #LB1900). These data support the potential utility of zanu in the frontline management of pts with TN CLL/SLL. Figure 1 Figure 1. Disclosures Tam: AbbVie: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Pharmacyclics: Honoraria; Novartis: Honoraria; Loxo: Consultancy; Roche: Consultancy, Honoraria. Giannopoulos: Polish Myeloma Consortium, Next Generation Hematology Association: Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy, Honoraria; Pfizer: Honoraria; Teva: Honoraria; TG Therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Astra-Zeneca: Consultancy, Honoraria, Research Funding; Bei-Gene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi-Genzyme: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Gilead: Honoraria, Research Funding. Jurczak: Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Research Funding; Bayer: Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celtrion: Research Funding; Celgene: Research Funding; Debbiopharm: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo Oncology: Membership on an entity's Board of Directors or advisory committees; Sandoz: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Epizyme: Research Funding; Incyte: Research Funding; Merck: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding. Šimkovič: Janssen, Gilead, Roche, AstraZeneca, and AbbVie: Other: consultancy fees, advisory board participation fees, travel grants, and honoraria; University Hospital Hradec Kralove: Current Employment; AbbVie: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Merck: Current equity holder in publicly-traded company; Eli Lilly: Current equity holder in publicly-traded company; J&J: Current equity holder in publicly-traded company; Gilead: Other: Travel, Accommodations, Expenses. Shadman: Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune , Mustang Bio and Atara Biotherapeutics: Consultancy; Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding. Österborg: BeiGene: Research Funding; Gilead: Research Funding. Laurenti: Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Gilead: Honoraria; Roche: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; BeiGene: Honoraria. Walker: BeiGene: Consultancy; Acerta: Consultancy. Opat: Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Sandoz: Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Monash Health: Current Employment. Chan: AbbVie: Membership on an entity's Board of Directors or advisory committees; Eusa: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Travel, Accommodations, Expenses; Celgene: Other: Travel, Accommodations, Expenses; Roche: Speakers Bureau. Ciepluch: Copernicus Wojewodzkie Centrum Onkologii: Current Employment. Greil: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Sandoz: Honoraria, Research Funding; Amgen: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Daiichi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding. Trněný: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees; MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; 1st Faculty of Medicine, Charles University, General Hospital in Prague: Current Employment; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Celgene: Consultancy; Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Gilead Sciences: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; AstraZeneca: Honoraria. Brander: Verastem: Consultancy; ArQule: Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Juno Therapeutics/Celgene/Bristol Myers Squibb: Research Funding; MEI Pharma: Research Funding; Novartis: Research Funding; LOXO: Research Funding; Ascentage: Research Funding; AstraZeneca: Research Funding; BeiGene: Research Funding; DTRM: Research Funding; AbbVie: Consultancy, Other: informCLL registry steering committee, Research Funding; Pfizer: Consultancy, Other: Biosimilars outcomes research panel; NCCN: Other: panel member; ArQule/Merck: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding. Flinn: Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Sarah Cannon Research Institute: Current Employment; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current holder of individual stocks in a privately-held company; Seattle Genetics: Research Funding. Verner: Janssen-Cilag Pty Ltd: Research Funding. Brown: Janssen: Consultancy; MEI Pharma: Consultancy; Rigel: Consultancy; Bristol-Myers Squib/Juno/Celegene: Consultancy; Novartis: Consultancy; Invectys: Other: Data Safety Monitoring Committee Service; TG Therapeutics: Research Funding; Abbvie: Consultancy; Acerta/Astra-Zeneca: Consultancy; Beigene: Consultancy; Catapult: Consultancy; Loxo/Lilly: Research Funding; Sun: Research Funding; Nextcea: Consultancy; Gilead: Research Funding; SecuraBio: Research Funding; Eli Lilly and Company: Consultancy; Genentech/Roche: Consultancy; Pfizer: Consultancy; Morphosys AG: Consultancy. Kahl: AbbVie, Adaptive, ADCT, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Celgene, Genentech, Incyte, Janssen, Karyopharm, Kite, MEI, Pharmacyclics, Roche, TG Therapeutics, and Teva: Consultancy; AbbVie, Acerta, ADCT, AstraZeneca, BeiGene, Genentech: Research Funding. Ghia: Sunesis: Research Funding; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Research Funding; Celgene/Juno/BMS: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; ArQule/MSD: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Acerta/AstraZeneca: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Tian: BeiGene: Current Employment; AbbVie: Ended employment in the past 24 months. Marimpietri: BeiGene USA: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Paik: BeiGene USA, Inc.: Current Employment, Current equity holder in publicly-traded company. Cohen: BeiGene: Current Employment, Current equity holder in publicly-traded company, Other: Travel, Accommodations, Expenses. Huang: BeiGene: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months, Other: Travel, Accommodations, Expenses; Protara Therapeutics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Robak: Biogen, Abbvie, Octapharma, Janssen: Honoraria, Other: Advisory board; AstraZeneca, Abbvie, Janssen, Octapharma, Gilead,Oncopeptides AB, Pharmacyclics, Pfizer, GlaxoSmithKline, Biogen: Research Funding; Medical University of Lodz: Current Employment. Hillmen: Pharmacyclics: Honoraria, Research Funding; Roche: Research Funding; Gilead: Research Funding; AstraZeneca: Honoraria; SOBI: Honoraria; BeiGene: Honoraria; AbbVie: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding. OffLabel Disclosure: Zanubrutinib is an investigational agent and has not been approved for TN CLL/SLL without del(17p) in the US

У роботі розглядаються теоретичні аспекти здійснення імпорту на зарубіжних ринках, визначається вплив внутрішнього та зовнішнього середовища на імпортну діяльність підприємства та методи її оцінки. Проаналізовано зовнішньоекономічну діяльність ТОВ «Тіксан», здійснено факторний і кореляційно-регресійний аналіз впливу чинників, що сприяють та заважають здійсненню імпортної діяльності. Розраховани показники стану та динаміки імпортної дільності. Запропоновано напрями вдосконалення імпортної діяльності підприємства, розроблено заходи щодо оптимізації імпорту та підвищення ефективності збуту і просування, зокрема шляхом диверсифікації ринків збуту та виробництва, використання можливостей.
The paper considers the theoretical aspects of imports in foreign markets, determines the impact of internal and external environment on the import activities of the enterprise and methods of its evaluation. The foreign economic activity of Tiksan LLC was analyzed, the factor and correlation-regression analysis of the influence of the factors that promote and hinder the implementation of import activity was carried out. Indicators of efficiency of import activity are calculated. The directions of improvement of the import activity of the enterprise are offered, measures on optimization of import and increase of efficiency of the logistic scheme of supply, in particular by diversification of the markets of sale and manufacture, use of possibilities of e-commerce are developed.