CXR severity as a predictor for post-COVID-19 related ILD

COVID-19 is caused by SARS COV-2, which first emerged in China and spread widely worldwide. Chest X-ray(CXR) is the first-line tool for COVID-19, and it allows initial assessment and follow-up, giving a great insight into the disease course. A high-resolution computed tomography (HRCT) has become essential for the diagnosis of postCOVID related interstitial lung disease (ILD). Our aim was to determine the COVID-19 disease severity using the CXR scoring system and then evaluate whether the severity of admission CXR could predict the presence of post-COVID related ILD. Data were analysed retrospectively for all adult patients presenting to our hospital between August 2020 and December 2021. 44 patients were found with post-COVID related ILD on HRCT which was performed as a result of persistent abnormalities on 6-12 week follow up CXR. We used severity scoring systems which were classified as mild, moderate, and severe depending on the number of lung segments involved. Severity scoring was performed by an experienced radiologist. Each CXR classification was then compared to HRCT findings. A total of 44 patients with COVID-19, 31 men and 13 women were included. The mean age was 67.7 (range 45-93). The following disease patterns were reported on HRCT: ground-glass opacities, traction bronchiectasis, reticulation, fibrosis, consolidation, organizing pneumonia, and honeycombing. When HRCTs were correlated, 18 admission CXRs were classified as mild, 23 as moderate and 3 as severe. This suggests that the severity of admission CXR does not predict the subsequent emergence of post-covid related ILD. We would recommend looking at other possible predictors such as the need for ventilatory support, comorbidities, and intensive care admissions.

A Study on an Understanding of Migrant Women's Empowerment and Their Perceptions Toward Participation in Park Management and Its Correlation

Background and objective: There have been an increasing number of migrant women in Korea. However, they are facing many difficulties in terms of language, psychology, poverty and many other things. Moreover, many mental health problems have emerged since COVID-19, to which migrant women have been more vulnerable. Alternatively, parks and green spaces have been a key to recovering mental health. In line with this, long-term management of green spaces has been raised as an issue to help promote people's health and empowerment. However, we have little evidence that the issue also conveys the empowerment of migrants and positivity through participation in park and green space management. Therefore, this study aims at 1) understanding migrant women's perception toward participation in park and green space management, 2) analyzing the correlation between empowerment and place-keeping, and 3) deriving implications. Methods: To address the objectives, this study conducts 1) a theoretical review of empowerment and place-keeping of migrant women through literature review and 2) a non-face-to-face survey targeting 108 migrant women. The collected data was analyzed using SPSS 26. Results: The results are as follows: 1) migrant women have highly positive perceptions toward participation in park and green space management, with statistical significance in funding and governance depending on the marital status, and 2) there is a significant correlation between place-keeping and empowerment in role and expression. This means that increasing the role and expression in empowerment can promote more active participation in park and green space management. Conclusion: In conclusion, in order to improve the empowerment of migrant women, they should be guided to actively participate in park and green space management and provided with the opportunity to participate in policy-making. © 2022 by the Society for People, Plants, and Environment.

Intracranial activity of dacomitinib in treatment naive advanced EGFR mutated non-small cell lung cancer (NSCLC): Prespecified subgroup analysis of the ATORG-003 trial

Background: Dacomitinib is a second generation EGFR tyrosine kinase inhibitor approved as first-line therapy in advanced EGFR mutated NSCLC. In the phase 3 ARCHER 1050 trial, PFS and OS were improved with dacomitinib compared to gefitinib. However, patients (pts) with central nervous system (CNS) metastases (mets) were ineligible to enroll into the study. ATORG-003 is an ongoing investigator-initiated single-arm phase 2 trial evaluating a dose titration strategy to improve the safety and tolerability of dacomitinib whilst maintaining efficacy. The intracranial activity of dacomitinib was evaluated in a prespecified subgroup analysis. Method(s): ATORG-003 (9 sites, 5 Asian countries) is enrolling newly diagnosed stage IIIB-IV NSCLC pts with EGFR mutations (exon 19 deletion [ex19del] or L858R). Pts receive dacomitinib 30 mg orally once daily for one cycle (4 weeks [wks]), after which pts with grade <=1 toxicity may escalate to 45 mg once daily (investigator/pt decision). A 24 pt subgroup with asymptomatic/controlled CNS mets completed enrollment in Jun2021. CNS mets were assessed by MRI scan at baseline and every 8 wks for 18 months (mo), then every 12 wks with MRI/CT. Key study secondary endpoints include intracranial objective response rate (iORR) and intracranial progression free survival (iPFS). Analyses were based on 7Jun2022 data cutoff date (median 18.7 mo follow-up). Result(s): Of 24 pts with CNS mets, median age was 65 years (range 33-78), ECOG PS 0/1 in 17%/83% and ex19del/L858R/both in 50%/46%/4%. 8/24 (33%) pts had prior intracranial radiotherapy. 2/24 pts dose escalated to 45 mg once daily after Cycle 1. There was measurable (>=10 mm target lesion) CNS mets in 9/24 (38%) pts. The iORR was 67% (1 intracranial CR [iCR], 5 intracranial PR), and median intracranial duration of response (iDoR) was not reached (NR). In 14 pts with non-measurable CNS mets only, iCR was seen in 6 (43%) pts. Median iPFS was NR with only n=5 CNS progression events in the entire cohort and n=7 remain on treatment. Overall (intra and extracranial) ORR was 67% and PFS rate at 12 mo was 42%. Conclusion(s): Dacomitinib has significant intracranial activity with observed durable responses in advanced EGFR mutated NSCLC with CNS mets. Clinical trial identification: NCT04027647. Legal entity responsible for the study: Asian Thoracic Oncology Research Group (ATORG). Funding(s): Pfizer. Disclosure: A. Tan: Financial Interests, Personal, Advisory Board: Amgen, Pfizer, Bayer. D. Kim: Financial Interests, Institutional, Principal Investigator: Alpha Biopharma, Amgen, Astrazeneca/Medimmune, Boehringer Ingelheim, BMS, Bridge BioTherapeutics, Chong Keun Dang, Daiichi-Sankyo, GSK, Hanmi, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan;Financial Interests, Institutional, Funding: InnoN, Asia Thoracic Oncology Research Group;Non-Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, BMS/ONO Pharmaceuticals, Daiichi-Sankyo, GSK, Janssen, Merck, MSD, Oncobix, Pfizer, SK Biopharm, Takeda;Financial Interests, Personal, Advisory Role: Scientific advisor for Health insurance review and assessment service, Korea;Non-Financial Interests, Personal, Leadership Role: Asian Thoracic Oncology Research Group, Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology. T. Baisamut (Reungwetwattana): Financial Interests, Personal, Advisory Board, and speaker: Astrazeneca, Pfizer, Roche, MSD, Novartis, BMS, Amgen;Financial Interests, Personal, Advisory Board: Yuhan;Financial Interests, Institutional, Invited Speaker: Astrazeneca, Roche, Novartis, MSD. L. Yueh Ni: Financial Interests, Personal, Other, Panel of Discussion for Hepatocellular Carcinoma: AstraZeneca;Financial Interests, Personal, Advisory Board, Advisory Board Meeting for early breast cancer management in our current practice.: Roche;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A multicentre, open-label, single-arm, lecular profiling study of patient with EGFR mutation-positive locally advanced or metastatic NSCLC treated with Osimertinib: AstraZeneca;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Phase 3 Double-blinded, Two-arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) versus Placebo as Adjuvant Therapy in Participants with Hepatocellular Carcinoma and Complete Radiological Response after Surgical Resection or Local Ablation (KEYNOTE-937): MSD;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Phase III, Randomized, Double-blind Study to Assess the Efficacy and Safety of Lazertinib versus Gefitinib as the First-line Treatment in Patients with Epidermal Growth Factor Receptor Sensitizing Mutation Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer: YUHAN;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A phase II randomized study of the combination of Ribociclib plus goserelin acetate with Hormonal Therapy versus physician choice chemotherapy in premenopausal or perimenopausal patients with hormone receptor-positive/HER2-negative inoperable locally advanced or metastatic breast cancer - RIGHT Choice Study: Novartis;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Global, Randomized, Phase 3, Open-Label Study of REGN2810 (Anti-PD-1 Antibody) versus Platinum-Based Chemotherapy in First-Line Treatment of Patients with Advanced or Metastatic PD-L1+ Non-Small Cell Lung Cancer: Regeneron;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Phase 3 study to Evaluate Zimberelimab (AB122) Monotherapy Compared to Standard Chemotherapy or Zimberelimab Combined with AB 154 in Front-Line, PD-L1 Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer: Arcus;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Prospective, Multicenter, Non-Interventional Genomic Profiling Study in Subjects with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) using Foundation Medicine: Roche;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Phase 3, randomize, double-blind trial of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) in participants with treatment naiv , metastatic non-small cell lung cancer (NSCLC) whose tumors have a tumor proportion score (TPS) greater than or equal to 1% (LEAP-007): MSD. G.F. Ho: Financial Interests, Personal, Advisory Board: Merck & Co., Inc., Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer;Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Pfizer, Merck & Co., Inc., Novartis, Roche, Boehringer Ingelheim;Financial Interests, Personal, Other, Chairperson: Bristol Myers Squibb;Financial Interests, Institutional, Invited Speaker: EliLily, Regeneron, Merck & Co., Inc., AB Science, Astellas, Tessa Therapeutics, Roche, Arcus Bioscience, AstraZeneca, Pfizer;Non-Financial Interests, Institutional, Product Samples: Pfizer, Eli Lilly, Novartis, Janssen Pharmaceuticals. L.M. Tho: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Roche, MSD, Pfizer. N. Prasongsook: Financial Interests, Personal, Advisory Board: Roche (Thailand), Novartis;Financial Interests, Personal, Invited Speaker: AstraZeneca. T.S.K. Mok: Financial Interests, Personal, Invited Speaker: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Fishawack Facilitate, InMed Medical Communication, Lunit USA, Inc., Merck Serono, MSD, Roche, MD Health, Medscape/WebMD, PeerVoice, Permanyer SL, Prime Oncology, Research to Practice, Touch Medical Media, Sanofi-Aventis, Takeda, PER, Daz Group, Janssen Pharmaceutical NV, Jiahui Holdings Co., LiangYiHui Healthcare, Lucence Health Inc., Merck Pharmaceuticals HK Ltd., MiRXES, Novartis, OrigiMed Co. Ltd., Pfizer, Shanghai BeBirds Translation & Consulting Co., Ltd., Taih harmaceutical Co., Ltd., AstraZeneca;Financial Interests, Personal, Advisory Board: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Blueprint Medicines, Berry Oncology, CStone Pharma, Daiichi Sankyo, Fishawack Facilitate, Eisai, Gritstone Oncology, Guardant Health, G1 Therapeutics, Hengrui, Ignyta, IQVIA, Incyte Corporation, Inivata, Janssen, Loxo Oncology, Qiming Dev., Lunit USA, Inc., Merck Serono, MSD, Roche, Mirati Therapeutics, MoreHealth, Novartis, OrigiMed, Puma Tech., Sanofi-Aventis, Takeda, Virtus Medical, Yuhan, Curio Science, Bayer Healthcare Pharmaceuticals Ltd., Covidien LP, C4 Therapeutics, Cirina Ltd., Da Volterrra, F. Hoffmann-La Roche Ltd./Genentech, Gilead Sciences, Lucence Health Inc., Medscape LLC / WebMD, MiRXES, OSE Immunotherapeutics, Pfizer, SFJ Pharmaceutical Ltd., Synergy Research, Tigermed, Vertex Pharmaceuticals, Berry Oncology, D3 Bio Ltd., Lakeshore Biotech;Financial Interests, Personal, Officer, Chairman: ACT Genomics-Sanomics Group;Financial Interests, Personal, Invited Speaker, Former known as Hutchison Chi-Med: HutchMed;Financial Interests, Personal, Stocks/Shares: Sanomics Ltd., Biolidics Ltd., Aurora Tele-Oncology, AstraZeneca;Financial Interests, Personal, Stocks/Shares, Former known as Hutchison Chi-Med: HutchMed;Financial Interests, Institutional, Funding, For clinical trials performed at CUHK: AstraZeneca, BMS, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology;Non-Financial Interests, Personal, Advisory Role: geneDecode;Non-Financial Interests, Personal, Other, Invited Speaker: AstraZeneca, Aurora Tele-Oncology, Lunit USA, Inc., Sanomics Ltd.;Non-Financial Interests,Personal, Leadership Role, Term ended on 30 June 2022: American Society of Clinical Oncology (ASCO);Non-Financial Interests, Personal, Leadership Role: Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), St. Stephen's College & Prep. School (Hong Kong);Non-Financial Interests, Personal, Leadership Role, Term ended: Chinese Society of Clinical Oncology (CSCO);Non-Financial Interests, Personal, Leadership Role, Term ended on 30 April 2019: International Association for he Study of Lung Cancer (IASLC). D.S.W. Tan: Financial Interests, Personal, Invited Speaker: Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda;Financial Interests, Personal, Advisory Role: Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli-Lilly, Loxo, GlaxoSmithKline, MSD;Financial Interests, Institutional, Funding: Novartis, AstraZeneca, Bayer, Pfizer, Amgen. H.H.F. Loong: Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, MSD;Financial Interests, Personal, Invited Speaker: Eli-Lilly, Illumina, Bayer, Guardant Health;Financial Interests, Personal, Advisory Board: Novartis, Takeda. All other authors have declared no conflicts of interest. Copyright © 2022

Role of Aerosols in Spring Blooms in the Central Yellow Sea During the COVID-19 Lockdown by China

Reduced amounts of aerosols blowing into the Yellow Sea (YS), owing to the temporary lockdown of factories in China during COVID-19, resulted in a 15% decrease in spring chlorophyll-a concentration (CHL) in March 2020 compared to its mean March values from 2003 to 2021. Particularly, the effect of land-based AOD is insignificant compared with that of atmospheric aerosols flowing into the YS, as indicated by the currents and wind directions. Hence, the main objective of this study was to understand the relationship between atmospheric aerosols and CHL by quantitatively considering relevant environmental changes using a Random Forest (RF) algorithm. Various input physical forcing variables to RF were employed, including aerosol optical depth (AOD), sea surface temperature (SST), mixed layer depth (MLD), wind divergence (WD), and total precipitation (TP). From the RF-based analysis, we estimated the relative contribution of each physical forcing variable to the difference in CHL during and after the COVID-19 lockdown period. The sensitivity of the RF model to changes in aerosol levels indicated positive effects of increased amounts of aerosols during spring blooms. Additionally, we calculated the quantitative contribution of aerosols to CHL changes. When SST was warmer and TP was lower than their climatology in March 2020, CHL increased by 0.22 mg m-3 and 0.02 mg m-3, respectively. Conversely, when MLD became shallower and AOD was lower than their climatology, CHL decreased as much as 0.01 mg m-3 and 0.20 mg m-3. Variations in WD caused no significant change in CHL. Overall, the specific estimations for reduced spring blooms were caused by a reduction in aerosols during the COVID-19 lockdown period. Furthermore, the RF developed in this study can be used to examine CHL changes and the relative role of significant environmental changes in biological blooms in the ocean for any normal year. Copyright © 2022 Baek, Park, Kim, Lee, Lee, Lee and Jo.

CML-466 Asciminib Provides Durable Molecular Responses in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With the T315I Mutation: Updated Efficacy and Safety Data From a Phase I Trial

CONTEXT: In CML-CP, the BCR::ABL1 T315I mutation confers resistance to previously approved ATP-competitive tyrosine kinase inhibitors (TKIs), except ponatinib and olverembatinib. In a previous analysis of the phase I, dose-escalation trial X2101, asciminib-a BCR::ABL1 inhibitor that binds to the ABL myristoyl pocket-demonstrated efficacy and a favorable safety profile in heavily pretreated patients with T315I-mutated CML. We report updated efficacy and safety data in patients with CML-CP with the T315I mutation (data cutoff: January 6, 2021). OBJECTIVE: Provide updated safety and efficacy data for patients with T315I-mutated CML-CP after added exposure. DESIGN: Patients with T315I-mutated CML-CP and treated with >=1 prior TKI were enrolled and received asciminib 200mg twice daily (BID). RESULTS: 48 patients were included;25 patients (52.1%) received >=3 prior TKIs. At data cutoff, treatment was ongoing in 27 patients (56.3%). 45 of 48 patients were evaluable (BCR::ABL1IS >0.1% at baseline) for major molecular response (MMR);3 were excluded for BCR::ABL1 atypical transcripts. Among evaluable patients, 19 (42.2%) achieved MMR by week 24 and 22 (48.9%) by week 96. Evaluable patients included 26 ponatinib-pretreated and 19 ponatinib-naive patients;34.6% and 68.4%, respectively, achieved MMR by week 96. The probability of maintaining MMR for >=96 weeks was 84% (95% CI, 68.1%-100.0%). 23 of 37 patients (62.2%) with BCR::ABL1IS >1% at baseline achieved BCR::ABL1IS <=1% by week 96. The safety/tolerability profile of asciminib remained favorable after =9 months of added exposure (median duration of exposure, 2.08 years;range, 0.04-4.13 years). The most common (>=10%) grade >=3 adverse events (AEs) were lipase increase (18.8%, all asymptomatic elevations) and thrombocytopenia (14.6%). Arterial occlusive events occurred in 4 patients (8.3%);none led to dose adjustment/interruption/discontinuation. AEs leading to discontinuation occurred in 5 patients (10.4%). Only 2 study deaths, both due to COVID-19, occurred in this patient population. CONCLUSIONS: After a median exposure of >2 years, asciminib monotherapy 200mg BID exhibited a sustained, favorable safety profile and clinical efficacy in patients with T315I-mutated CML-CP-a population with high unmet medical need. This updated analysis confirms asciminib as a treatment option for patients with T315I-mutated CML-CP, including those previously treated with ponatinib.

ASCIMINIB PROVIDES DURABLE MOLECULAR RESPONSES IN PATIENTS (PTS) WITH CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE (CML-CP) WITH THE T315I MUTATION: UPDATED EFFICACY AND SAFETY DATA FROM A PHASE I TRIAL

Background: In pts with CML, the BCR::ABL1 T315I mutation is associated with poor clinical outcomes and confers resistance to previously approved ATP-competitive tyrosine kinase inhibitors (TKIs). Until recently, ponatinib (PON) was the only TKI available for these pts, but its use may be limited by associated cardiovascular events. In the primary analysis of the phase I trial X2101, asciminib-the 1st BCR::ABL1 inhibitor to Specifically Target the ABL Myristoyl Pocket (STAMP)-demonstrated efficacy and a favorable safety profile in heavily pretreated pts with CML with T315I. These results supported the FDA approval of asciminib as a new treatment option for pts with CML-CP with T315I (NCCN 2021). We report updated efficacy and safety data in these pts (data cutoff: January 6, 2021). Aims: Provide updated safety and efficacy data for pts with CML-CP with T315I treated with asciminib monotherapy 200 mg twice daily (BID) after added exposure. Methods: Pts with CML-CP with T315I were enrolled if treated with ≥1 prior TKI and no other effective therapy was available, provided informed consent, and received asciminib 200 mg BID. Results: 48 pts with T315I were included;2 (4.2%) pts had additional BCR::ABL1 mutations at baseline. Eight (16.7%), 15 (31.3%) and 25 (52.1%) pts received 1,2, and ≥3 prior TKIs, respectively. At data cutoff, treatment was ongoing in more than half (27 [56.3%]) of pts;the predominant reason for treatment discontinuation was physician's decision (11 [22.9%]), mainly due to lack of efficacy. Of the 48 pts, 45 were evaluable (BCR::ABL1IS >0.1% at baseline) for major molecular response (MMR);3 were excluded for BCR::ABL1 atypical transcripts. Among evaluable pts, 19 (42.2%) achieved MMR by wk 24 and 22 (48.9%) by wk 96;19 were still in MMR at the cutoff date. Evaluable pts included 26 PON-pretreated and 19 PONnaive pts;34.6% and 68.4%, respectively, achieved MMR by the cutoff date (Table). The probability of pts maintaining MMR for ≥96 wks was 84% (95% CI, 68.1-100.0). Thirteen (28.9%) and 11 (24.4%) pts achieved MR4 and MR4.5, respectively. Twenty (54.1%) and 23 (62.2%) of 37 pts with BCR::ABL1IS >1% at baseline achieved BCR::ABL1IS ≤1% by wk 48 and 96, respectively. The median duration of exposure was 2.08 (range, 0.04-4.13) yrs with more than half (27 [56.3%]) of pts receiving treatment for ≥96 wks;the median daily dose intensity was 398.3 (range, 179-400) mg/day. The safety/tolerability profile of asciminib remained favorable after ≈9 months of added follow-up (Table). The most common (≥5%) grade ≥3 adverse events (AEs) were lipase increase (18.8%, all asymptomatic elevations), thrombocytopenia (14.6%), and vomiting, ALT increase, abdominal pain, hypertension, anemia, neutropenia, and neutrophil count decrease (6.3% each). Arterial occlusive events occurred in 4 (8.3%) pts;none led to dose adjustment/interruption/discontinuation. AEs leading to discontinuation were reported in 2 new pts since the previous data cutoff;both pts discontinued and died due to COVID-19. These were the only study deaths reported in this pt population. Image: Summary/Conclusion: Asciminib monotherapy 200 mg BID exhibited a sustained, favorable safety profile after added exposure with no new safety signals in pts with CML-CP with T315I-a population with high unmet medical need. The clinical efficacy of asciminib is demonstrated by the high proportion of pts achieving durable MMR and BCR::ABL1IS ≤ 1%. The updated analysis confirms asciminib as a treatment option for pts with CML-CP with T315I, including those for whom treatment with PON has failed.

CHANGING PERFORMANCE OF COLORECTAL CANCER SCREENING FOLLOWING A COVID-19 PANDEMIC IN KOREA

Background/Aim: It is easy to predict that the actual COVID-19 pandemic would have had a negative impact on cancer screening activities and the outcomes of screenings, but to date, real-time population-based evidence to substantiate this concern is very scarce. In this study, to understand the changes in the behavior and performance of CRC screening following the COVID-19 pandemic, the indicators of CRC screening processes and outcome measures were compared with both monthly data in 2019 and monthly changes focusing on the peaks that appeared in 2020. Method: This population-based nationwide study used fecal immunochemical test (FIT) and colonoscopy claims data from the Korean National Health Insurance System (NHIS) from 2019 to 2020. Data were analyzed from 15,867,759 subjects in 2019 and 16,155,930 subjects in 2020. We compared the data of CRC screening (FIT/ colonoscopy) of the COVID-19 pandemic period (2020) with those of the same period of 2019. Result: In the COVID-19 period, 3,445,660 (21.3%) subjects underwent FIT, whereas in 2019, 6,490,707 (40.9%) subjects performed FIT (almost 2-fold). Participation rate in colonoscopy after FIT positive fell in 2020 by 36.0% compared with the average rate recorded in 2019 (44.5%). In particular, it was confirmed that the participation rate of the CRC screening further decreased immediately after the COVID-19 peak periods (first and second wave: March 2020 and August 2020). Conclusion: The overall adherences to CRC screening tests decreased substantially during COVID-19 pandemic. Therefore, urgent modulation for not only easier access but also planning a restart for CRC screening is needed to address the growing burden of under-detected CRC in Korea.

An update of safety and efficacy results from phase 1 dose-escalation and expansion study of vodobatinib, a novel oral BCR-ABL1 tyrosine kinase inhibitor (TKI), in patients with chronic myeloid leukemia (CML) and philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ All) failing prior tki therapies

Introduction: Vodobatinib is a novel third generation TKI effective against wild-type and mutated BCR-ABL1 (except T315I) with limited off-target activity. We present updated results from the Phase 1 dose-escalation (DEs) and expansion (DEx) study in CML and Ph+ALL patients (pts) failing ≥ 3 prior TKIs (< 3 prior TKIs if approved TKI is not clinically advised or available);patients with T315I are not eligible (NCT02629692). Methods: This is an open-label, phase 1, multicentre, 3+3 study evaluating maximum tolerated dose (MTD), safety and efficacy of vodobatinib administered once daily in 28 day cycles (dose range: 12 to 240 mg). MTD was established at 204 mg. DEx study enrolled chronic phase CML (CP-CML) patients at 174 mg dose of vodobatinib. Treatment continued until unacceptable toxicity, disease progression, consent withdrawal or death. Adverse events were assessed using NCI-CTCAE v4.03. Results: As of 15 Jul 2021, 52 pts are enrolled in DEs and DEx cohorts. Forty one of these pts received doses from 12 to 240 mg in the DEs cohort;32 chronic phase (CP-CML), 3 accelerated phase CML (AP-CML), 4 blast phase CML (BP-CML), 2 Ph+ ALL. Eleven CPCML pts were enrolled in DEx cohort at 174 mg dose. The baseline demographics and disease history are represented in Table 1. Efficacy: Of the 32 CP-CML pts enrolled in DEs: At baseline, 21 (65%) pts had no cytogenetic response, 4 (12.5%) were in PCyR, 7 (22%) were in CCyR. On vodobatinib therapy, 11(34%) pts achieved CCyR, 3 (9%) achieved PCyR and 7 (22%) maintained baseline CCyR. Baseline major molecular response (MMR) was present in 1 (3%) pt;and 14 pts (44%) achieved MMR on study. Of the remaining 11 pts, 5 (16%) had haematologically stable disease (no CyR and molecular response) and 6 (19%) had disease progression (cytogenetic or hematological) as their best response (Table 2 and 3). Seventeen CP-CML pts had prior ponatinib treatment, of which 11 (65%) had MCyR (4 achieved CCyR, 4 maintained CCyR, 3 achieved PCyR);while 8 (47%) achieved MMR. In the remaining 15 pts ponatinib naïve CP-CML: 10 (66%) had CCyR (7 achieved CCyR, 3 maintained CCyR);with 7 (47%) with MMR (6 achieved, 1 maintained). Two of the 3, AP-CML pts had baseline hematological response (CHR) with absence of cytogenetic and molecular response. The 3 pts further deepened their responses with 1 pt achieving CCyR with MMR and 2 pts in PCyR. Of the 4 BP-CML pts, 2 achieved CHR and 2 patients had disease progression as their best response;Of the 2 Ph+ ALL pts, 1 pt maintained CCyR and MMR while the other reported disease progression as the best response. Median duration of treatment overall was 23 (0.5-51) months [CP-CML 23 (0.5-51);AP-CML 36 (9-40);BP-CML 3 (0.5-18) and Ph+ ALL 4 (0.7-7.3) months]. Twenty one pts continue in study. In the DEx cohort, 1 of the 11 CP-CML pts was in PCyR at baseline. No pts had molecular response. Of the 11 patients, 6 (54 %) pts achieved CCyR, 1(10%) pt achieved PCyR. MMR was achieved by 1 pt (10%). Data is maturing for 1 pt. Median duration of treatment is 16 (0.3-19) months and 10 pts continue in study. Safety: Forty nine of 52 pts reported at least 1 TEAE. Most common any grade TEAEs included thrombocytopenia (33%), cough (19%), anaemia & diarrhoea (17% each). Thirty one pts (60%) reported Grade 3 and 4 treatment emergent AEs: most common were thrombocytopenia (15%), neutropenia and anaemia (12%), increased amylase and lipase (8% each). Ten (19%) pts reported cardiovascular TEAEs (Grade 1: angina pectoris, palpitations, ventricular extra-systoles, arteriosclerosis, hot flush, hypotension, intermittent claudication;Grade 2: hypertension, hypotension;Grade 3: cardiac failure congestive, hypertension);with a Grade 2 hypertension being vodobatinib related. Nineteen pts (37%) reported SAEs;vodobatinib related SAEs were reported in 3 pts (fatal intracranial haemorrhage (ICH), Grade 2 back pain and Grade 3 amnesia reported in 1 pt each). There were 5 deaths on study: 1 was related to use of vodobatinib (1 ICH, confounded by disease progression to blast phase that include extra-medullary sites) and the remaining unrelated (1 sudden death, 1 disease progression, 1 pneumonia fungal, 1 suspected COVID-19). Conclusion: Vodobatinib continues to be associated with favourable long term safety and efficacy in heavily pre-treated CML failing ≥ 3 prior TKIs, including ponatinib. Phase 2 study evaluating vodobatinib in pts failing at least 3 prior lines of therapy, including ponatinib, is ongoing.

Phase Ib study of BI 836880 (VEGF/Ang2 inhibitor) plus ezabenlimab (BI 754091;anti-PD-1 antibody) in patients (pts) with advanced hepatocellular carcinoma (HCC)

Background: Combination of anti-VEGF compounds and immune checkpoint inhibitors is an approved therapy across multiple solid tumors, including advanced HCC. This phase Ib study (NCT03468426) is assessing BI 836880 (bispecific VEGF/Ang2 nanobody) + ezabenlimab (anti-PD-1 antibody) in pts with advanced solid tumors. The recommended phase 2 dose (RP2D) of BI 836880 720 mg + ezabenlimab 240 mg given IV every 3 weeks was determined in Part 1. In Part 2, RP2D was assessed in 7 expansion cohorts. We report data from cohorts in HCC after prior sorafenib/lenvatinib (cohort F) and untreated unresectable HCC (cohort G). Methods: Pts with locally advanced or metastatic HCC, Child-Pugh class A, not eligible for surgical or locoregional therapies were enrolled. Cohort F enrolled pts who had progressed on or after first-line treatment with sorafenib or lenvatinib or who had discontinued due to poor tolerability after ≥2 weeks of treatment. Cohort G enrolled pts who had received no prior systemic therapy for HCC. Treatment continued until disease progression, undue toxicity or consent withdrawal. Primary endpoint is objective response rate (ORR) by RECIST 1.1. Results: As of Aug 2021, 30/31 pts have been treated in cohorts F/G: 87/77% male;median age 65/64 yrs. Follow-up is ongoing in both cohorts. 9/19 pts in cohorts F/G remain on treatment;median (range) duration of treatment is 175 (42-532)/ 169 (42-336) days in cohorts F/G. All pts were evaluable for response in cohort F: confirmed ORR to date is 40% (1 complete response;11 partial responses [PRs]). Of 28 evaluable pts in cohort G, confirmed ORR to date is 21% (6 PRs). 12 (40%) pts in cohort F and 18 (64%) in cohort G have stable disease. In cohort F, AEs were reported in 28 (93%) pts, most frequently hypertension and proteinuria (each 30%). In cohort G, AEs occurred in 26 (84%) pts, most frequently ascites (26%) and thrombocytopenia (19%). 24 (80%) pts in cohort F and 15 (48%) in cohort G had treatmentrelated AEs (TRAEs). Most frequent TRAEs were proteinuria (27%), infusion-related reactions (IRRs) and hypertension (each 20%) in cohort F, and hypertension (13%), IRRs, hypothyroidism and diarrhea (each 10%) in cohort G. There were 3 pts with G5 AEs in cohort F (COVID-19 pneumonia [n = 1];low Glasgow coma score and dyspnea [n = 1];hepatic cirrhosis [n = 1]) and 1 G5 AE in cohort G (hepatic failure);none were considered related to treatment. AEs leading to discontinuation occurred in 2 pts in cohort F (G3 hepatic encephalopathy and G2 duodenal ulcer) and 3 in cohort G (G5 hepatic failure [n = 1];G2 acute kidney injury and G1 decreased appetite [n = 1];G2 diarrhea [n = 1]). Conclusions: BI 836880 + ezabenlimab had a manageable safety profile and showed promising activity in pts with untreated and second-line post-sorafenib/lenvatinib advanced HCC. Data continue to mature, particularly in cohort G. Cohort F has been expanded by a further 30 pts.

Phase Ib study evaluating BI 836880 (VEGF/Ang2 nanobody) in combination with ezabenlimab (BI 754091;anti-PD-1 antibody) in patients with solid tumours

Background: Combining anti-VEGF/Ang2 and anti-PD-1 therapy promotes an immunopermissive state, supportive of T-cell-mediated tumour cell destruction. This phase Ib study is assessing BI 836880 plus ezabenlimab in patients (pts) with advanced solid tumours. In Part 1 (dose escalation in pts with advanced NSCLC), the recommended phase 2 dose (RP2D) was determined as BI 836880 720 mg + ezabenlimab 240 mg IV q3w. Here, we report updated results, including data from Part 2 (expansion cohorts). Methods: Part 2 has 7 cohorts: metastatic (m) NSCLC after checkpoint inhibitor (CPI) monotherapy (Cohort A);mNSCLC after chemotherapy (CT) + CPI (Cohort B);mSCLC after CT ± CPI (Cohort C);recurrent GBM (1st and 2nd recurrence;Cohort D);immunotherapy-resistant m-melanoma (Cohort E);HCC after prior sorafenib or lenvatinib (Cohort F);and previously untreated unresectable HCC (Cohort G). Primary endpoint is objective response rate (complete response [CR] + partial response [PR]). Results: As of March 2021, 215 pts have been treated (Part 1: 14, Part 2: 201 [Cohort A, 35;B, 32;C, 19;D, 31;E, 32;F, 29;G, 23];70% male, median age 62 yrs). Any and ≥G3 AEs (any-cause) were reported in 183 (85%) and 72 (33%) pts. 118 (55%) pts had drug-related AEs, most commonly asthenia (13%) and hypertension (12%). 7 pts had G4 AEs (non-related hyperkalaemia + cardiac arrest, laryngospasm, gastrointestinal perforation;drug-related anaphylactic reaction, cholestatic hepatitis, acute pancreatitis, increased transaminases);9 pts had G5 AEs (non-related COVID-19 pneumonia, epilepsy, intracranial haemorrhage, cardio-respiratory arrest, haemoptysis, hepatic failure, general physical health deterioration, Glasgow coma scale abnormal + shortness of breath;drug-related tracheal haemorrhage). 35 (16%) pts had immune-related AEs and 15 (7%) had AEs leading to discontinuation. 179 pts were evaluable for response: 1 had confirmed CR (Cohort F), 22 had PR (Part 1: 2;Part 2: 20 [Cohort A, 4;C, 5;D, 4;E, 3;F, 3;G, 1]) and 110 had stable disease. 106 pts remain on treatment. Conclusions: BI 836880 plus ezabenlimab had a manageable safety profile, with preliminary activity in a range of tumour types. Clinical trial identification: NCT03468426. Editorial acknowledgement: Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Hannah Simmons MSc, of Ashfield MedComms, an Ashfield Health company, and funded by Boehringer Ingelheim. Legal entity responsible for the study: Boehringer Ingelheim. Funding: Boehringer Ingelheim. Disclosure: N. Girard: Financial Interests, Personal, Advisory Role: Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, BMS, MSD, Takeda, GSK, AbbVie, Pharmamar, Janssen, Sanofi;Financial Interests, Personal, Funding, Travel/accommodation/expenses: Roche, AstraZeneca, BMS MSD Oncology;Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, Boehringer Ingelheim. M. Wermke: Financial Interests, Personal, Advisory Role: MSD, Novartis, Kite, Heidelberg Pharma, Roche, Boehringer Ingelheim;Financial Interests, Personal, Other, Honoraria: BMS, Merck, Roche, Novartis, Kite, Boehringer Ingelheim, AstraZeneca;Financial Interests, Personal, Funding, Travel/Accommodation/Expenses: Glenmark, BMS, AstraZeneca. E. Ledin: Financial Interests, Personal and Institutional, Research Grant: Boehringer Ingelheim. D. Kim: Financial Interests, Personal, Advisory Role: Health Insurance Review & Assessment Service, Korea;Financial Interests, Personal, Invited Speaker: Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology, Taiwan Lung Cancer Society;Financial Interests, Institutional, Principal Investigator, Clinical Trial Funding: Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer-Ingelheim, Bridge BioTherapeutics, Chong Keun Dang, Daiich-Sankyo, GSK, Hanmi, Janssen, Merus, MIrati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeuti;Non-Financial Interests, Person l, Advisory Role: Amgen, AstraZeneca, BMS / ONO Pharmaceuticals, Daiich-Sankyo, GSK, Janssen, Pfizer, SK Biopharm, Takeda, Yuhan;Non-Financial Interests, Personal, Member of the Board of Directors: Asian Thoracic Oncology Research Group, Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology;Other, Personal, Funding, Travel support for advisory board meeting attendance: Amgen, Daiichi-Sankyo. J. Bennouna: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, MSD, AstraZeneca, Roche, Servier, Bayer, AMGEN;Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, MSD, AstraZeneca, Roche;Financial Interests, Institutional, Research Grant: AstraZeneca. T. Lesimple: Financial Interests, Personal, Advisory Role: MSD, Novartis, BMS, Pierre Fabre;Financial Interests, Personal, Speaker’s Bureau: MSD, Novartis;Financial Interests, Institutional, Research Grant: Roche. E. Felip: Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: BAYER;Financial Interests, Personal, Advisory Board: Beigene;Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim;Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb;Financial Interests, Personal, Advisory Board: Eli Lilly;Financial Interests, Personal, Advisory Board: F. Hoffman-La Roche;Financial Interests, Personal, Advisory Board: Glaxo Smith Kline;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Advisory Board: Medical Trends;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Board: Merck Serono;Financial Interests, Personal, Advisory Board: Peptomyc;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Puma;Financial Interests, Personal, Advisory Board: Regeneron;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: Syneos Health;Financial Interests, Personal, Advisory Board: Takeda;Financial Interests, Personal, Speaker’s Bureau: Amgen;Financial Interests, Personal, Speaker’s Bureau: AstraZeneca;Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb;Financial Interests, Personal, Speaker’s Bureau: Eli Lilly;Financial Interests, Personal, Speaker’s Bureau: F. Hoffmann-La Roche;Financial Interests, Personal, Speaker’s Bureau: Janssen;Financial Interests, Personal, Speaker’s Bureau: Medscape;Financial Interests, Personal, Speaker’s Bureau: Merck Sharp & Dohme;Financial Interests, Personal, Speaker’s Bureau: Merck Serono;Financial Interests, Personal, Speaker’s Bureau: Peervoice;Financial Interests, Personal, Speaker’s Bureau: Pfizer;Financial Interests, Personal, Speaker’s Bureau: Springer;Financial Interests, Personal, Speaker’s Bureau: Touch Medical;Financial Interests, Personal, Member, Independent Member of the Board: Grífols. D. Berz: Financial Interests, Personal, Other, Honoraria: Oncocyte;Other, Personal, Other, Honoraria: Sun Pharma;Other, Personal, Other, Honoraria: Caris;Other, Personal, Other, Honoraria: Takeda;Other, Personal, Other, Honoraria: Natera;Other, Personal, Other, Honoraria: Jazz Pharma;Other, Personal, Other, Honoraria: Genentech;Financial Interests, Personal, Advisory Role: Oncocyte;Other, Personal, Advisory Role: Sun Pharma;Other, Personal, Advisory Role: Biocept;Other, Personal, Advisory Role: Prelude;Financial Interests, Personal, Speaker’s Bureau: Oncocyte;Other, Personal, Speaker’s Bureau: Caris;Other, Personal, Speaker’s Bureau: Sun Pharma;Other, Personal, Speaker’s Bureau: AstraZeneca;Other, Personal, Speaker’s Bureau: Takeda;Other, Personal, Speaker’s Bureau: Merck;Other, Personal, Speaker’s Bureau: Natera;Other, Personal, Speaker’s Bureau: Jazz Pharma. C. Mascaux: Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Astr Zeneca;Financial Interests, Personal, Advisory Role: Kephren;Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb;Financial Interests, Personal, Advisory Role: MSD;Financial Interests, Personal, Advisory Role: Pfizer;Financial Interests, Personal, Other, Honoraria: Roche;Financial Interests, Personal, Other, Honoraria: AstraZeneca;Financial Interests, Personal, Other, Honoraria: Kephren;Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb;Financial Interests, Personal, Other, Honoraria: MSD;Financial Interests, Personal, Other, Honoraria: Pfizer;Financial Interests, Personal, Other, travel, accommodations, expenses: Roche;Financial Interests, Personal, Other, travel, accommodations, expenses: AstraZeneca;Financial Interests, Personal, Other, travel, accommodations, expenses: Boehringer Ingelheim;Financial Interests, Personal, Other, travel, accommodations, expenses: Takeda. M. Voskoboynik: Financial Interests, Personal, Advisory Role: AstraZeneca. H.T. Landsteiner: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. V. Chen: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. G. Jayadeva: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. J. Alt: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, BMS, Pfizer, Roche, Takeda;Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, BMS, Roche;Financial Interests, Personal, Funding, Travel/accommodation/expenses: AstraZeneca, Boehringer Ingelheim, BMS. B. Hackanson: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, MSD, AstraZeneca, BMS. All other authors have declared no conflicts of interest.

Phase 1 Trial of Vodobatinib, a Novel Oral BCR-ABL1 Tyrosine Kinase Inhibitor (TKI): Activity in CML Chronic Phase Patients Failing TKI Therapies Including Ponatinib

Introduction: Vodobatinib, a novel 3rd generation (3G) TKI effective against wild-type and mutated BCR-ABL1 with limited off-target activity, was evaluated in a Phase I multicentre dose-escalation study in chronic myeloid leukemia (CML) patients (pts) who failed ≥ 3 TKIs or less (if not eligible for other approved 3G TKIs) (NCT02629692). The activity and safety of vodobatinib was evaluated in ponatinib treated (PT) and ponatinib naïve (PN) chronic phase (CP)-CML subjects in an exploratory analysis. Methods: Multiple escalating doses of vodobatinib (once daily) in 28-day cycles were evaluated in a 3+3 study design. The primary objective was determination of the maximal tolerated dose (MTD) or recommended phase 2 dose (RP2D) along with safety and a secondary objective was to evaluate anti-leukemic activity. Dose escalation involved dose doubling until 2 pts in a cohort experienced Grade 2 toxicity, or 1 pt experienced Grade 3 or 4 toxicity, after which dose escalation was reduced to 40% increments. Treatment continued until unacceptable toxicity, disease progression (PD), consent withdrawal, or death. Results: As of 15 Jul 2020, 31 CP-CML pts received vodobatinib at doses of 12 to 240 mg;16 pts (9 males) in ponatinib treated (PT) cohort [7 (44%) ponatinib was the immediate prior TKI] and 15 pts (7 males) in the ponatinib naïve (PN) cohort. The baseline demographics and disease history are represented in Table 1. Efficacy: Median duration of treatment was 17.3 (0.6-36) and 14.8 (0.5- 42) months in the Ponatinib treated and naive groups, respectively;11 pts in the PT group [2 in Deep molecular response (DMR), 3 in MMR;5 in MCyR (2 in CCyR and 3 in PCyR);1 in stable disease] and 10 pts in the PN group (2 in DMR, 4 in MMR and 3 in CCyR, 1 in stable disease) are continuing on treatment. Overall efficacy outcomes are included in Tables 2 and 3. Of 16 PT pts, 2 (13%) pts, both with double mutations, had disease progression. Of 15 PN pts, 4 (26%) pts (with baseline mutation of T315I at 48 mg, Y253H at 66 mg, F317L and E255V mutation at 174 mg) progressed. Safety: In ponatinib treated pts, the most commonly reported treatment emergent adverse events (TEAEs), (all grades) included nausea (4, 25%) and diarrhea (3, 25%). Other commonly reported TEAEs included thrombocytopenia (3, 19%), rash (3, 19%), non-cardiac chest pain (3, 19%), increased amylase (3, 19%), and fall (3, 19%). Grade ≥ 3 TEAEs were reported in 10 (63%) pts included 1 pt each with anemia, lymphopenia, fall, skull fracture, spinal fracture, lipase increase, fluid overload, syncope, dyspnea, and hypertension. Vodobatinib related AEs included amylase increase, lipase increase, dyspnea, fluid overload, thrombocytopenia and neutropenia. Grade ≥ 3 TEAEs reported in more than one pt included neutropenia (2, 13%) amylase increase (2, 13%) and thrombocytopenia (2, 13%). In PN pts, the most commonly reported TEAEs (all grades) included myalgia (5, 33%) and back pain (4, 27%). Other commonly reported TEAEs were thrombocytopenia (4, 27%), and nasopharyngitis (3, 20%).Grade ≥ 3 TEAEs were reported in 7 (47%) pts (1 pt with anemia, 1 pt with pneumonia, 1 pt with neutropenia, 1 pt with gout, hypokalemia, thrombocytopenia, 1 pt with increased liver and pancreatic enzymes and 1 pt each with dementia and amnesia. Vodobatinib related AEs included alanine aminotransferase increase, blood bilirubin increased, amnesia, neutropenia and thrombocytopenia. No grade ≥ 3 event was reported in more than 1 pt. Overall, three cardiovascular TEAEs were reported, in 2 pts (1 each in PT and PN), all deemed unrelated to vodobatinib. Three pts died on study: 1 due to disease progression in the PT group;1 due to pneumonia (suspected COVID-19) and 1 due to intracranial hemorrhage in the PN group. The intracranial hemorrhage event (Grade 5 AE) was considered possibly related and was confounded by disease progression to blast phase that included extra-medullary sites. At the highest dose of 240 mg, two dose limiting toxicities were reported. The next lower dose level of 204 mg was est blished as MTD with a favorable safety profile in heavily pre-treated CP-CML pts. Conclusion: Vodobatinib was evaluated over 9 escalating doses. Comparable and promising efficacy was noted in both PT (50% CCyR) and PN (67% CCyR) groups, meriting further study of vodobatinib as a potential new agent for treatment of previously treated CP-CML. [Formula presented] Disclosures: Cortes: Daiichi Sankyo: Consultancy, Research Funding;Jazz Pharmaceuticals: Consultancy, Research Funding;Immunogen: Research Funding;Merus: Research Funding;Bristol-Myers Squibb: Research Funding;Takeda: Consultancy, Research Funding;Sun Pharma: Research Funding;BioPath Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Telios: Research Funding;Astellas: Research Funding;Amphivena Therapeutics: Research Funding;Arog: Research Funding;BiolineRx: Consultancy, Research Funding;Pfizer: Consultancy, Research Funding;Novartis: Consultancy, Research Funding. Kim: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Takeda: Research Funding;BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Sun Pharma.: Research Funding;Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau;ILYANG: Consultancy, Honoraria, Research Funding. Alvarado: BerGenBio ASA: Research Funding;MEI Pharma: Research Funding;Astex Pharmaceuticals: Research Funding;Sun Pharma: Research Funding;FibroGen: Research Funding;Tolero Pharmaceuticals: Research Funding;Jazz Pharmaceuticals: Research Funding;Daiichi-Sankyo: Research Funding. Nicolini: Sun Pharma Ltd: Consultancy;Incyte: Research Funding, Speakers Bureau;Novartis: Research Funding, Speakers Bureau. Apperley: Bristol Myers Squibb: Honoraria, Speakers Bureau;Incyte: Honoraria, Research Funding, Speakers Bureau;Novartis: Honoraria, Speakers Bureau;Pfizer: Honoraria, Research Funding, Speakers Bureau. Deininger: DisperSol: Consultancy;Pfizer: Honoraria, Other, Research Funding;Leukemia & Lymphoma Society: Research Funding;Ariad: Consultancy, Honoraria, Other;Medscape: Consultancy;Novartis: Consultancy, Other, Research Funding;Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Fusion Pharma: Consultancy;Blueprint Medicines Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: part of a study management committee, Research Funding;Incyte: Consultancy, Honoraria, Other, Research Funding;Sangamo: Consultancy, Membership on an entity's Board of Directors or advisory committees;SPARC: Research Funding;Gilead Sciences: Research Funding;Bristol-Myers Squibb: Consultancy, Honoraria, Other, Research Funding;Galena: Consultancy, Honoraria, Other;Celgene: Research Funding. de Lavallade: Incyte: Honoraria, Research Funding;Bristol Myers Squibb: Honoraria, Research Funding;Novartis: Honoraria;Pfizer: Honoraria. Charbonnier: Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartts: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gambacorti-Passerini: Pfizer: Honoraria, Research Funding;Bristol-Myers Squibb: Consultancy. Lucchesi: Pfizer: Honoraria;Incyte: Honoraria;Novartis: Honoraria. Mauro: Takeda: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding;Novartis: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding;Sun Pharma/SPARC: Research Funding;Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding;Pfizer: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding. Whiteley: Novartis: Consultancy;Dova: Consultancy;Jazz: Speakers Bureau;Seattle Genetics: Consultancy Speakers Bureau;GlaxoSmithKline: Speakers Bureau;Epizyme: Current equity holder in publicly-traded company, Speakers Bureau;Karyopharm: Current equity holder in publicly-traded company;Aprea: Current equity holder in publicly-traded company;MorphoSys: Consultancy;Agios: Consultancy, Speakers Bureau;Pfizer: Consultancy;Rigel: Consultancy. Yao: Sun Pharma Industries Incorporated: Current Employment. Kothekar: Sun Pharma Advanced Research Company Limited: Current Employment. Sreenivasan: Sun Pharma Advanced Research Company Limited: Current Employment. HV: Sun Pharma Advanced Research Company Limited: Current Employment. Chimote: Sun Pharma Advanced Research Company Limited: Current Employment.

Phase Ib study of BI 836880 (VEGF/Ang2 nanobody) plus ezabenlimab (BI 754091;anti-PD-1 antibody) in patients (pts) with solid tumors

Background: In preclinical studies, the combination of anti-VEGF/Ang2 and anti-PD-1 therapy has been shown to promote an immunopermissive state, which is supportive of T-cell-mediated tumor cell destruction. BI 836880 is a humanized bispecific nanobody that targets VEGF and Ang2, and ezabenlimab (BI 754091) is an anti-PD-1 antibody. Phase I studies investigating each as monotherapies have reported safety and preliminary antitumor activity. This ongoing Phase Ib study is evaluating the combination of BI 836880 and ezabenlimab in pts with advanced solid tumors. In Part 1 (dose escalation), the combination was feasible in pts with advanced NSCLC, with a recommended Phase II dose (RP2D) of BI 836880 720 mg + ezabenlimab 240 mg IV q3w. Here, we report updated results from Part 2 (expansion phase), which is assessing the antitumor activity and safety of the RP2D. Methods: Seven cohorts are currently recruiting pts in Part 2: metastatic (m) NSCLC after checkpoint inhibitor (CPI) monotherapy (Cohort A);mNSCLC after chemotherapy (CT) + CPI (Cohort B);mSCLC after CT ± CPI (Cohort C);1 and 2nd recurrences of glioblastoma (GBM;Cohort D);immunotherapy-resistant mmelanoma (Cohort E);hepatocellular carcinoma (HCC) after prior sorafenib or lenvatinib ± CPI (Cohort F);and previously untreated/unresectable HCC (Cohort G). Primary endpoint is objective response rate (complete response + partial response [PR]). Results: As of January 2021, 196 pts have received BI 836880 plus ezabenlimab (14 in Part 1, 182 in Part 2 [Cohort A, 26;B, 30;C, 19;D, 31;E, 32;F, 28;G, 16]). 134 (68%) pts were male, median age was 63 years and 102 (52%) had prior CPI use. Any grade and ≥G3 adverse events (AEs;any cause) were reported by 160 (82%) and 62 (32%) pts, most commonly (all%/ ≥G3%) hypertension (20/8), asthenia (20/3), diarrhea, decreased appetite, and nausea (all 11/1). 95 (48%) pts had a drug-related AE, most commonly hypertension and asthenia (both 11%). 6 pts had a G4 AE (non-related: hyperkalemia + cardiac arrest, laryngospasm, gastrointestinal perforation;drug-related: anaphylactic reaction, acute pancreatitis, transaminases increased);8 pts had a G5 AE (non-related: general physical health deterioration, epilepsy, hemoptysis, cardiorespiratory arrest, hepatic failure, intracranial hemorrhage, COVID-19 pneumonia;drugrelated tracheal hemorrhage). 30 (15%) pts had immune-related AEs (3% ≥G3), including hypothyroidism (3%). 11 (6%) pts had an AE leading to discontinuation. Overall, 145 pts were evaluable for response: 9 pts achieved confirmed PR (2 pts in Part 1 and 7 in Part 2 [NSCLC, n = 3;SCLC, n = 1;GBM, n = 1;melanoma, n = 1;and 2 -line HCC, n = 1]), 87 pts had stable disease and 49 pts had progressive disease. 111 pts remain on treatment. Conclusions: BI 836880 plus ezabenlimab had a manageable safety profile. The combination showed preliminary antitumor activity in a range of tumor types.

Viral stimulation modulates endotype-related ACE2 expression in eosinophilic chronic rhinosinusitis.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2), a receptor targeted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the nasal mucosa. Chronic rhinosinusitis (CRS) shows diverse endotypes and is aggravated by viral infection. Whether viral stimulation and CRS endotype influence ACE2 expression remains unclear. We investigated the expression of ACE2 and the transmembrane protease, serine 2 (TMPRSS2), which mediate the entry of SARS-CoV-2 into cells, and assessed polyinosinic:polycytidylic acid (poly[I:C])-induced changes based on CRS endotype. METHODOLOGY: ACE2 and TMPRSS2 expression was evaluated based on CRS phenotype, endotype, and tissue type. Correlations between ACE2/TMPRSS2 expression and inflammatory mediators in nasal polyps (NP) were examined. Air-liquid interface culture experiments were performed to assess the effects of major cytokines or poly(I:C) stimulation on ACE2/TMPRSS2 expression in primary epithelial cells from healthy nasal mucosa, eosinophilic NP (ENP), and non-eosinophilic NP (NENP). RESULTS: In primary nasal epithelial cells, interleukin (IL)-13 decreased ACE2 expression but increased TMPRSS2. Eosinophilic CRS showed lower ACE2 expression than non-eosinophilic CRS, regardless of CRS phenotype. CRS endotype was an independent factor associated with ACE2/TMPRSS2 expression in NP. Serum and tissue eosinophilic marker levels were inversely correlated with ACE2 expression, whereas tissue neutrophilic marker levels and ACE2 expression were positively correlated in NP. ACE2 expression was suppressed in ENP tissues; however, a combination of poly(I:C) and IL-13 induced ACE2/TMPRSS2 upregulation in ENP. CONCLUSIONS: ENP tissues have lower ACE2 expression than NENP; however, viral stimulation promotes ACE2/TMPRSS2 upregulation in ENP.

Netnography Analysis of Consumer Sentiment Towards Panic Buying In The Early Period of the COVID-19 Virus Spread

COVID-19 has not only an impact on health aspects but also other issues, including the economy. At times of crisis that is full of challenges, individuals who prefer to compelled to do what needs to protected from the negativity caused by the disaster. One who managed to save himself in times of crisis caused a panic of buying that happens a lot in retail stores. Companies must study the efforts made by buyers related to panic buying that is happening around them. Companies can explore these insights through sentiments formed from social media user posts on social media platforms. This research explores consumer sentiment related to panic purchases using qualitative analysis with NVivo software. The results of a study of 647 posts on Twitter microblogging revealed that panic buying contained negative attitude. Based on the results of this analysis, there are tactical steps that can be taken by companies in supporting individual efforts to protect themselves from losses caused by the COVID-19 outbreak.