Citations

Abstract Since the beginning of the COVID-19 pandemic, vulnerable populations such as pregnant persons have been at higher risk of severe symptoms and poor outcomes. Although reports of SARS-CoV-2 vertical transmission remain rare, several studies showed that maternal infection during pregnancy can induce histomorphological and inflammatory alterations in the placenta. However, the permissiveness of human trophoblasts to various variants of the virus remains poorly characterized. In this study, human primary villous cytotrophoblasts isolated from term placentas, along with trophoblastic cell lines BeWo, JEG-3, and HIPEC-65 were infected with the ancestral SARS-CoV-2 strain, which disseminated worldwide in early 2020. Permissiveness was assessed with quantitative RT-PCR, immunostaining of viral protein Nucleocapsid, and plaque assays. To investigate viral entry routes, cells were treated with Camostat mesylate (an inhibitor of the co-entry factor TMPRSS2) or chloroquine phosphate (an endosomal entry inhibitor) and viral fitness was assessed by plaque assays. Primary villous cytotrophoblasts and JEG-3 cells were also tested for infection with three pre-omicron SARS-CoV-2 variants of concern. Our results show that primary villous cytotrophoblasts are permissive to all tested SARS-CoV-2 strains in vitro. Infection with the ancestral SARS-CoV-2 strain relies mainly on a non-canonical endosomal entry pathway. Notably, JEG-3 cells represent an appropriate and convenient model for studying trophoblast infection by SARS-CoV-2, as they exhibit high permissiveness to the ancestral strain, and the SARS-CoV-2 entry pathway is similar to that in villous cytotrophoblasts. Overall, this study reveals that the cytotrophoblastic permissiveness to SARS-CoV-2 depends on the viral genetic nature and provides new insights into its entry route in human trophoblasts.

ABSTRACT Background Preoperative vascular embolization (PVE) is commonly used in managing juvenile nasopharyngeal angiofibroma (JNA) to improve outcomes. However, few studies have evaluated how embolization patterns and vascular features affect prognosis. Methods A 15‐year retrospective review was performed on 44 patients with JNA undergoing surgery at one institution. Data included demographics, vascular supply, embolization techniques, surgical outcomes, and recurrence. Results Forty‐three patients underwent PVE. Most tumors were embolized transarterially (93.0%) using polyvinyl alcohol‐based agents (79.1%). The internal maxillary artery was most commonly embolized (93.0%). Internal carotid artery supply was present in 34.9%, and more than two vessels were embolized in 23.3%. Postembolization tumor blush occurred in 60.5%, with a median of 5% of the pre‐embolization blush remaining after embolization. Neither internal carotid involvement, number of vessels embolized, nor residual blush significantly impacted operative time, surgical outcomes, or recurrence. Conclusion With effective embolization, vascular complexity might not affect JNA resection outcomes. Multicenter studies are required to confirm those findings.

Abstract PURPOSE: CDK4/6 inhibitors (CDK4/6i), used in combination with endocrine therapy (ET), are standard of care for advanced and higher risk early stage hormone receptor-positive (HR+), HER2 negative (HER2-) breast cancer. PALLAS investigated the addition of 2 years (y) of palbociclib to adjuvant ET (ET/P) compared to ET alone in patients (pts) with stage II-III HR+/HER2- breast cancer. We now present overall survival (OS) with 7-y outcomes and impact of post-recurrence therapy. PATIENTS AND METHODS: This global phase III trial randomized pts to ET for at least 5 y with or without 2 y of P. Primary endpoint was iDFS; distant recurrence-free survival (DRFS) and OS were preplanned endpoints. Kaplan Meier estimates and hazard ratios (HR) from Cox and Fine & Gray models were performed. Post-recurrence OS was analyzed as time from first distant recurrence (DR) until death. The post-recurrence OS model adjusted for both clin/path factors (including DR-free y, DR site) and time-dependent post-DR therapy (chemo, CDK4/6i). Results: 5,796 pts enrolled at 406 centers in 21 countries worldwide over 3 y. In the intent-to-treat (ITT) population, with a median follow-up of 82.7 months (mo), 7-y outcomes for iDFS, DRFS and OS are shown in the table. DR occurred in 781 pts (377 ET/P, 404 ET alone) with balanced pt/disease characteristics between arms. ET/P had more visceral (46% vs. 36%) and fewer non-visceral (61% vs. 68%) DR compared to ET alone (p=0.03). Unadjusted post-recurrence OS was significantly worse for ET/P vs. ET (median 22.6 vs. 27.9 mo, HR 1.21 (95% CI 1.01-1.46, p=0.04). However, receipt of any post-recurrence CDK4/6i was significantly higher on ET vs. ET/P arms (41% vs. 66%) and time to post-progression CDK4/6i initiation was significantly shorter for those in the ET vs. ET/P arms (HR 0.50, 95% CI 0.41-0.61, p<0.001) adjusting for region, bone/visceral DR type, DR-free time and age. Conversely, time to post-progression chemotherapy initiation was significantly longer for ET alone vs. ET/P arms (HR 1.31, 95% CI 1.07-1.61, p=0.01). However, after adjustment for clinical factors and post-DR treatment, the OS difference was no longer seen (HR 1.05, 95% CI 0.85-1.28, p=0.65). 3-mo landmark analysis showed similar effect on OS after adjusting for CDK4/6i initiation within 3 mo from DR (unadjusted HR 1.24, p=0.03 vs. adjusted HR 1.15, p=0.22). CONCLUSION: The PALLAS trial revealed significant differences in treatment post-DR that impact OS. Reduced/delayed use of metastatic CDK4/6i after adjuvant P was associated with significantly poorer OS, suggesting that patients who relapse after adjuvant CDK4/6i may still benefit from metastatic CDK4/6i. This has implications for optimal treatment in those who relapse after adjuvant CDK4/6i and warrants further study to determine if this is therapy-specific or an overarching biological effect. SUPPORT: AFT, ABCSG, NRG, PrECOG; Pfizer Citation Format: A. DeMichele, A. Dueck, M. Gnant, D. Hlauschek, M. Martin, A. Wolff, G. Rubovsky, F. Henao, O. Hahn, A. Chan, A. Brusky, P. Morris, H. Burstein, G. Huber, D. Anderson, L. Garcia-Estevez, G. Pfeiler, H. Rugo, N. Zdenkowski, S. Gampenrieder, N. Wolmark, D. Sabanathan, K. Miller, D. Cameron, E. Winer, C. Brunner, E. Gauthier, P. O’Brien, C. Fesl, E. Mayer. Adjuvant Palbociclib for ER+ Breast Cancer in the PALLAS Trial (ABCSG-42/AFT-05/PrE0109/BIG-14-13): Post-Recurrence Treatment and Overall Survival [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF7-07.

Abstract Background PALLAS trial compared palbociclib plus endocrine therapy (ET) vs. ET alone in stage II-III HR+/HER2- breast cancer. SETER/PR index quantifies transcriptional activity related to estrogen and progesterone receptors and serves as a measure of endocrine sensitivity. In CALGB 9741, low SETER/PR (< 0.75) - reflecting endocrine resistance - predicted survival benefit from adjuvant anthracycline/taxane-based treatment. In PALLAS low SETER/PR was associated with worse prognosis and early recurrence. Early recurrences driven by endocrine-resistant tumors may obscure the benefit of palbociclib by disproportionately contributing events from a more resistant population. We hypothesized that palbociclib efficacy might vary by endocrine sensitivity and prior chemotherapy regimen, with greatest benefit in patients with intermediate SETER/PR index. Methods Invasive disease-free survival (iDFS) was summarized with Kaplan-Meier plots and the treatment arms were compared with a log-rank test. Cox models estimated the hazard ratio (HR) with 95% confidence interval (95%CI) (significance level used was a two-sided 0.05). SETER/PR index was successfully obtained for 3,090 PALLAS patients (TransPALLAS ITT cohort, Metzger et al. ASCO 2024). SETER/PR index cut points (0.75 and 1.50) were proposed from previous studies comparing different adjuvant chemotherapy regimens. Results Table 1 summarizes the efficacy of adjuvant palbociclib by prior (neo)adjuvant chemotherapy regimen. Palbociclib was associated with longer iDFS in the group who received prior anthracycline-paclitaxel chemotherapy (AC-P), though the chemo regimen x palbociclib interaction term was not significant (Table 1). In the 1,132 patients from the TransPALLAS cohort who received AC-P chemotherapy, the 518 (46%) patients with intermediate SETER/PR (0.75≤ SETER/PR <1.50) had longer iDFS with palbociclib (HR 0.58; 95% CI: 0.40-0.84; p=0.004; 7-yr iDFS 80.2% vs. 68.4%), but this subset did not predict palbociclib benefit relative to all others, i.e., 206 (18%) patients with low SETER/PR (<0.75) and 408 (36%) high SETER/PR (≥1.50); P interaction=0.11. Exploratory analysis of SETER/PR index as a continuous variable in patients who received prior AC-P chemotherapy revealed a non-linear relationship with the hazard ratio favoring palbociclib observed in the subset with SETER/PR values between 1.1 and 1.8, compared to all others (P interaction=0.01). Conclusions In PALLAS, we observed a numerical benefit favoring palbociclib among pts treated with adjuvant AC-P; in this subset a moderate level of endocrine transcriptional activity (SETER/PR index between 1.1 and 1.8) predicted palbociclib benefit. These results are hypothesis-generating. Citation Format: O. Metzger, P. O'Brien, K. Ballman, M. Gnant, M. Watson, E. Chen, K. Tran, D. Hlauschek, M. Martin, J. Balko, Z. Nowecki, O. Hahn, C. Denkert, C. Curtis, F. Liu, A. Dueck, C. Fesl, E. Mayer, A. De Michele, W. Symmans. Exploratory analysis of palbociclib benefit in the PALLAS trial by SETERPR index and prior chemotherapy regimens (ABCSG-42/AFT-05/BIG-14-13) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-08-13.

Abstract Introduction Serial assessments of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) provide independent prognostic significance for progression free survival and overall survival. A low CTC burden (<5 CTCs / 7.5mL blood) at baseline is favorable prognostically, and reduction of CTCs during treatment indicates response to treatment (Janni, CCR 2025). Despite increasing evidence supporting its clinical validity, real-time serial CTC enumeration has not been utilized broadly in clinical practice in the U.S. The ACT-MBC study is a prospective observational study to evaluate the impact of serial CTC testing on treatment decisions and response assessment (NCT05662345). Provider (physician or advanced practitioner) perception of CTC testing is measured with questionnaires at baseline (PQ1), and for each pt during the first restaging visit (PQ2), and at the end of the study (PQ3). We previously reported PQ1 results (Giridhar, SABCS 2024). Here, we report on results of PQ2. Methods ACT-MBC prospectively enrolled patients (pts) at Mayo Clinic Rochester and Mayo Clinic Health Systems sites (Mankato, Albert Lea and Eau Claire). Pts with MBC were enrolled at time of progressive disease during any line of therapy (TNBC) or ≥2nd line metastatic therapy for ER+/HER2- disease. Pts were tested for CTCs using the FDA-cleared CellSearch® assay which included enumeration and biomarker testing on CTCs for ER, HER2, and PD-L1. The treating clinician determined the regimen and timing of restaging scans. CTC testing was performed once per cycle (every 3-4 weeks) with results returned to the treating provider within 7 days. We descriptively summarized PQ2 responses from providers who had at least one on-treatment CTC result available by the first restaging visit. We report the proportion (90% CI) of providers who agreed or strongly agreed that assessing CTCs enhanced their ability to determine response to therapy and that the CTC results helped guide their decision to continue or change therapy (co-primary endpoints) while accounting for within provider correlation. Results As of June 25, 2025, 15 providers enrolled a median of 2 pts each (range: 1 to 15 pts) and completed PQ2 surveys on 40 pts. 7 providers (47%) practiced in the community setting and 4 (27%) were nurse practitioners. Most pts were female (98%), White (98%), and had ER+/HER2- MBC (80%). Baseline (C1) CTC results were elevated (≥5 CTCs) in 24 (60%) pts (CTC range 0-609). At C2 (n=39), CTC values remained undetected in 7 pts, decreased in 21 pts, increased in 8 pts, and remained unchanged in 3 pts. At PQ2 (n=40), based on clinician interpretation of radiographic findings, results showed 2.5% of pts with complete response, 20% with partial response, 25% with stable disease, 17.5% with mixed response, and 35% with progressive disease. Clinicians reported that CTC results were concordant with imaging results in 34 (85%) responses, discordant with imaging in 7.5% of responses, and unclear in the remaining 7.5% of responses. Most clinicians (82.5%) agreed or strongly agreed that assessing CTCs enhanced their ability to determine response to therapy (90% CI: 68.3%, 96.7%). Further, 70% of providers agreed or strongly agreed that the CTC results helped guide their decision to continue or change therapy (90% CI: 50.8%, 89.2%). 32.5% of the time, CTCs results influenced the timing of the first restaging scans. In 11/25 pts without progressing disease, CTC results influenced the timing of future scans. In the 7/8 pts with a mixed response at first restaging scans with decreasing CTCs, 4 remained on the same systemic therapy. Conclusions Oncologists in academic and community practice responded that serial CTC assessments enhance ability to determine response of therapy, guide decisions to continue or change treatments, and influence timing of radiographic assessments. Citation Format: K. V. Giridhar, D. Zahrieh, M. Hanna, A. Singh, E. Al-Hattab, P. Schumacher, J. Carroll, J. Hoppenworth, T. Haddad, A. Tevaarwerk, B. Rudder, G. M. Choong, S. Basu, R. A. Leon-Ferre, T. O'Brien, A. Lewis, F. de Snoo, L. Stork-Sloots, F. K. Kuhr, S. Lazaro, R. Prendergast, D. S. Spinner, M. P. Goetz. Assessing the impact of real-time serial circulating tumor cell results on the management of patients with metastatic breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-03-10.

Abstract Background Colonic strictures in Crohn’s disease (CD) are an important, but understudied clinical problem. Cross-sectional imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and intestinal ultrasound (IUS) effectively assess the small bowel in CD allowing for the diagnosis of strictures. However, radiologic definitions of colonic strictures and their diagnostic accuracy have not been developed. Endoscopic definitions of colonic strictures are the most well-described. Aims We aimed to systematically review available data to summarize definitions, diagnosis and differentiation between inflammation and fibrosis of colonic strictures on endoscopy, CT, MR, and IUS Methods We conducted a systematic review following PRISMA guidelines using MEDLINE, Scopus, CINAHL, and CENTRAL databases from inception to Oct 6, 2024 to identify literature with diagnostic imaging that included patients with colonic CD strictures. To distinguish fibrosis from inflammation, only studies comparing endoscopy or imaging to a full thickness histologic gold standard were included. Two stage screening was completed in duplicate, and risk of bias was assessed using QUADAS-2 Results 46 studies were eligible for inclusion. Definitions for colonic strictures on CT, MR, and IUS are heterogeneous with combinations of bowel wall thickness, luminal narrowing, and pre-stenotic dilation with no clear cut offs. Endoscopic definitions commonly included lack of colonoscope passage through a narrowed lumen. The diagnostic accuracy of colonic strictures on imaging to detect inflammation and fibrosis against a gold standard of endoscopy or surgical resection is unclear as direct comparisons are few. Meta-analyses were not conducted due to methodological heterogeneity of grading fibrosis and statistical heterogeneity of sensitivity, specificity, and accuracy of colonic stricture diagnoses limited by pooling with small bowel strictures in the studies Conclusions This systematic review describes a lack of definitions for the diagnosis of CD colonic strictures particularly on diagnostic imaging, and the limitations with the current available data to differentiate inflammation from fibrosis. Although bowel wall thickening, luminal narrowing, and pre-stenotic dilation are recognized as hallmark features of small bowel strictures, their adaptation to the colon requires further assessment. Definitions for colonic strictures should likely include imaging combined with endoscopy. Future endeavors are required to develop a consensus to define and diagnose colonic strictures on these modalities Funding Agencies None

This cohort study evaluates the reduction in risk of high-grade serous carcinoma among women undergoing opportunistic bilateral salpingectomy in Canada.

Background Cysteine–cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), respectively. This phase 1b/2, open-label study evaluated BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy±nivolumab in advanced PDAC or metastatic CRC. Methods Part 1 included patients with metastatic untreated (first-line (1L)) PDAC, 1L CRC, or previously treated (second or third line (2/3L)) microsatellite stable (MSS) CRC. Patients received 2 weeks of BMS-813160 monotherapy (300 mg two times a day, 600 mg once daily, 300 mg once daily, or 150 mg once daily) and then BMS-813160+chemotherapy (gemcitabine+nab-paclitaxel (gem/nabP; 1L PDAC), 5-fluorouracil+leucovorin+irinotecan (FOLFIRI; 1L CRC)), or nivolumab (2/3L MSS CRC). Part 2 included patients with metastatic 1L PDAC or 2L CRC. Patients received BMS-813160 300 mg two times a day+gem/nabP±nivolumab (1L PDAC), BMS-813160 300 mg two times a day or 150 mg once daily+FOLFIRI (2L CRC), or chemotherapy alone. Primary endpoints were safety and pharmacodynamics (Part 1) and efficacy (Part 2). Results In Part 1, 22 of 75 (29%) and 54 of 72 (72%) patients experienced a treatment-related adverse event during monotherapy lead-in and overall, respectively. Two dose-limiting toxicities (rash and pericardial effusion with pericarditis, both grade 3) occurred. In Part 2, patients with 1L PDAC who received BMS-813160 300 mg two times a day+gem/nabP+nivolumab achieved an overall response rate (ORR) of 37% (13/35); the median duration of response (DOR) was 45 weeks (95% CI 26.1 to not evaluable). ORRs with BMS-813160 300 mg two times a day+gem/nabP and gem/nabP alone were 26% (9/35) and 28% (9/32), respectively; median DORs were 121 and 31 weeks, respectively. Progression-free survival rates at 24 weeks were 56% (BMS-813160 300 mg two times a day+gem/nabP+nivolumab), 56% (BMS-813160 300 mg two times a day+gem/nabP), and 50% (gem/nabP). ORRs in 2L CRC were 19% (6/32; BMS-813160 300 mg two times a day+FOLFIRI), 13% (4/32; BMS-813160 150 mg once daily+FOLFIRI), and 27% (7/26; FOLFIRI). Conclusions In 1L PDAC, BMS-813160 300 two times a day+gem/nabP±nivolumab demonstrated durable antitumor response and was well tolerated. BMS-813160 combination regimens were tolerable in other cohorts, but clinical efficacy was not demonstrated. Trial registration number NCT03184870 .

Abstract Background Colonic strictures in Crohn’s disease (CD) present a complex and relatively underexplored clinical issue. Imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and intestinal ultrasound (IUS), have established criteria for evaluating small bowel CD strictures. However, radiologic definitions of benign colonic strictures and their diagnostic accuracy are not well-developed. Endoscopic definitions of colonic strictures are the most well-described. We conducted a systematic review to summarize definitions, diagnosis, and identification of inflammation and fibrosis of colonic strictures on endoscopy, CT, MR, and IUS. Methods A systematic review following PRISMA guidelines, from inception to October 6, 2024, was conducted using MEDLINE, Scopus, CINAHL, and CENTRAL databases to identify literature on diagnostic imaging of patients with colonic CD strictures. Only studies with comparison to endoscopy or imaging to a full-thickness histologic gold standard to differentiate fibrosis from inflammation were included. Two stage screening was completed in duplicate, and risk of bias was assessed using QUADAS-2. Results 46 studies were eligible for inclusion of 4623 abstracts screened. Definitions of colonic strictures on CT, MR, and IUS were highly variable with combinations of bowel wall thickness, luminal narrowing, and pre-stenotic dilation. Endoscopic definitions of colonic strictures were the most consistently reported as lack of passage of a colonoscope through a narrowed lumen. Diagnostic imaging definitions used various combinations of increased bowel wall thickness, luminal narrowing, and pre-stenotic dilation with no clear cutoffs. Few studies directly compared imaging features with histologic or endoscopic gold standards, limiting evaluation of diagnostic accuracy. Meta-analyses were not conducted due to methodological heterogeneity of grading fibrosis across studies. In addition, statistical heterogeneity of sensitivity, specificity, and accuracy of colonic stricture diagnoses was limited by pooling with small bowel strictures in the studies. Conclusion This systematic review highlighted the absence of standardized definitions for diagnosing colonic Crohn’s disease strictures, particularly on diagnostic imaging, and the limited data distinguishing inflammatory from fibrotic components. Bowel wall thickening, luminal narrowing, and pre-stenotic dilation are key features of small bowel strictures, but their relevance to the colon requires further assessment. Establishing standardized definitions for colonic strictures that incorporate both endoscopic and imaging modalities is essential to advancing the field. Conflict of interest: Dr. Lu, Cathy: Advisory board - Abbvie, Johnson and Johnson, Takeda, Ferring, Merck, Celltrion, Lilly, Pfizer, Pendopharm, Agomab. Research Funding - Abbvie, Helmsley Charitable Trust, Alberta Innovates Dhaliwal, Ravdip: No conflict of interest Kellar, Amelia: No conflict of interest Rowan, Catherine: No conflict of interest St-Pierre, Joelle: Consultant for Pfizer, Abbvie, Eli Lilly and Pendopharm, and speaker for Takeda. Ernest-Suárez, Kenneth: Consulting/Advisory Board fees: Abbvie, AstraZeneca, Johnson & Johnson, Pfizer, Ferring, Sandoz, SatisfAI, Takeda O’Brien, Maureen: No conflict of interest Rosentreter, Ryan: No conflict of interest Gulhati, Vishrut: No conflict of interest Baker, Mark: No conflict of interest Bettenworth, Dominik: DB is on the advisory board or consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED-Service GmbH, Celltrion, Doctorflix, DGVS, Diaplan, Else Kröner-Fresenius Foundation, Falk Foundation, Galapagos, Guidepoint, Impulze, Ferring, Janssen Cilag, Lilly, Medical Tribune, MedTriX, MSD, Mylan, Onkowissen, Pharmacosmos, Pfizer, Roche, Sandoz, Takeda, Tetrameros, Thieme, Tillotts Pharma, UCB Biopiharma, Viatris and Vifor Pharma. Bruining, David: Advisory board fees from Janssen Bari, Dane: Grant from Helmsley Charitable Trust speaker honorarium from Siemens Healthineers support for attending meetings or travel from Siemens Healthineers member of the Olympus advisory board co-chair Society of Abdominal Radiology (SAR) Inflammatory Bowel Disease Disease Focused Panel (IBD DFP) and SAR Photon-Counting Detector CT Emerging Technology Commission and chair of the Society for Advanced Body Imaging Scientific Committee. Dillman, Jonathan: Grants from Philips Healthcare, GE HealthCare, Motilent, Perspectum, Guerbet, and Bracco. El Ouali, Sara: Speaker and/or consulting fees from Takeda, Eli Lilly, Janssen, Abbvie. Fletcher, John: Grant supports from Siemens Healthineers Gordon, Ilyssa: Grants to institution from Morphic Therapeutics, Alimentiv, Pliant Therapeutics, and UCB patent pending with Case Western Reserve University on radiomics signatures Jairath, Vipul: Consulting Fees: Abbvie, Alimentiv, Amgen, Anaptys Bio, Asahi Kasei, Asieris, Astra Zeneca, Attovia, Blackbird Labs, BMS, Boehringer Ingleheim, Biomebank, Caldera, Calluna, Catalytic Health, Celltrion, Ensho, Enthera, Exeliome Biosciences, Ferring, Fresenius Kabi, Gilead, Granite Bio, GSK, Janssen, Lilly, Merck, Mountainfield, MRM Health, Nxera, Organon, OSE Immunotherapeutics, Pendopharm, Pioneering Medicine, Pfizer, Prometheus, Roche/Genentech, Sanofi, SCOPE, Shattuck Labs, Sorriso, Spyre, Synedgen, Takeda, Teva, Tillotts, Union Therapeutics, Ventus, Ventyx, Vividion, Xencor, Zealand Pharma. Feagan, Brian Gordon: Consulting Fees: AbbVie, Abivax, Adaxion, Adiso, AgomAB Therapeutics, Akros, Alira Health, Ally Bridge Group, Apini Therapeutics, Argenx, Attovia Tx, Avoro Capital Advisors, Belmore Law, Biora Therapeutics, Blackbird Laboratories, Boehringer-Ingelheim, BMS, Boxer Capital, Celgene/BMS, Clarivate, Connect Biopharm, EcoR1, Eli Lilly, Ensho Therapeutics, Equillium, Evida, Enveda, Evommune Inc. Faes Farma, First Wave, Forbion, Galapagos, Genentech/Roche, General Atlantic, Genesis Therapeutics, Gerson Lehrman Group, Gilead, Guidepoint, Imhotex, ImiDomics, Immunic Therapeutics, Janssen, Japan Tobacco Inc., LifeMine Therapeutics, Mage Biologics, Merck, Mirador Therapeutics, Mobius Care, Monte Rosa Tx, Morphic Therapeutics, Nimbus Therapeutics, Novartis, Nxera, OncoC3, Palisade Bio, Pendopharm, Pfizer,Q32 Bio, REDX, Roche, Sanofi, Sobi, Sorriso, Spyre Therapeutics, Sun Pharma, Surrozen Inc., Synedgen, Takeda, Tegus Inc., Teva, Tillotts, Trex Bio, TR1X Inc. TVM Lifesciences, Ventyx Biosciences, Versant Ventures, Vida Ventures, Ysios Capital, Zagbio Stock Shareholder: Connect Biopharm, EnGene, Evida, SRT, Imidomics, Enveda Rieder, Florian: Personal Fees: Adiso, Adnovate, Agomab, Allergan, AbbVie, Arena, Astra Zeneca, Boehringer-Ingelheim, Celgene/BMS, Celltrion, CDISC, Celsius, Cowen, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Granite, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis Limited, Index Pharma, Landos, Jannsen, Koutif, Mestag, Metacrine, Mopac, Morphic, Organovo, Origo, Palisade, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Sanofi, Surmodics, Surrozen, Takeda, Techlab, Teva, Theravance, Thetis, UCB, Ysios, 89Bio

Abstract Background Risankizumab (RZB), a high-affinity humanised IgG1 monoclonal antibody targeting interleukin-23 p19, has demonstrated sustained efficacy, with a consistent safety profile supporting long-term use for patients (pts) with ulcerative colitis (UC).1-3 This interim analysis reports efficacy and safety through open-label extension (OLE) week (wks) 96 (3 years [yrs] of total maintenance) from the COMMAND OLE. Methods The OLE enrolled RZB-treated pts who completed the 52-wk maintenance substudies and/or responded to 12/24-wk induction therapy.1 All pts received subcutaneous RZB 180 mg (RZB180) starting at OLE wk 0, except those who received prior OLE RZB rescue therapy (1 RZB 1200 mg intravenous dose then RZB 360 mg [RZB360] every 8 wk) and continued RZB360 for 96 wks. Efficacy endpoints (clinical remission [CR] per Adapted Mayo Score [AMS], CR per Partial AMS [PAMS], corticosteroid-free CR per PAMS, clinical response per AMS, clinical response per PAMS, endoscopic improvement, and endoscopic remission) were assessed at OLE wks 0 and 96 and reported as observed (AO) prior to OLE RZB rescue therapy and nonresponder imputation (NRI), among the overall population and by inadequate response to advanced therapy (AT-IR vs non-AT-IR; data cutoff: 25Aug2025). The safety analysis included pts who received at least 1 dose of OLE RZB, with data presented as events/100 pt-yrs. Results At OLE wk 0, approximately 90% pts (N = 1003) completed the study visit; some differences were observed in the clinical characteristics of RZB180 and RZB360-treated pts, including mean AMS (2.0, 3.4); a numerically higher proportion of RZB360-pts were AT-IR (63.1%, 76.8%), and had an endoscopic score of ≥ 3 (12.1%, 31.1%). A lower proportion of RZB360-treated pts achieved CR per AMS (54.8%, 25.2%) at OLE wk 0, while a higher proportion of RZB360-treated pts received OLE rescue therapy (RZB180, 22.1%; RZB360, 34.5%). Efficacy rates remained stable at OLE wks 0 and 96 for CR per AMS; similar results were observed within each subgroup, AT-IR and non-AT-IR (Table 1). Numerically lower efficacy rates were observed in the AT-IR vs non-AT-IR pts at wk 96; efficacy was sustained through OLE wk 96 for all endpoints (AO, NRI; Table 1). Similar rates were observed for any adverse event (AE), severe AE, and serious AE in RZB180 and RZB360-treated pts. No new safety risks were identified in either treatment group (Table 2). Conclusion In the ongoing COMMAND OLE, sustained clinical and endoscopic benefit was observed in pts receiving up to 3 yrs of long-term RZB maintenance therapy, with numerically lower efficacy rates observed for AT-IR vs non-AT-IR vs pts. The long-term safety of RZB remains consistent with a favorable benefit-risk profile, supporting its long-term use in UC. References: 1.Louis E et al. JAMA. 2024;332:881-97. 2.Atreya R et al. J Crohn’s Colitis. 2025;19(S1):i108-i110. [Abstract]. 3.Panaccione R et. al. J Crohn’s and Colitis. 2025, 19(1):jjaf005. Conflict of interest: Atreya, Raja: RA has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, Arena Pharmaceuticals, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Dr Falk Pharma, Galapagos, Gilead, GlaxoSmithKline, InDex Pharmaceuticals, Johnson & Johnson, Lilly, Materia Prima, Merck Sharpe & Dohme, Pfizer, Roche Pharma, Takeda Pharma, Viatris. Louis, Edouard: Education and Reserach Grants for my department: Abbvie, Takeda, Johnson and Johnson, Pfizer, Fresenius-Kabi, Celltrion, EG pharma, Sandoz, Falk Personal Fees for conferences, advisory boards and consultancy: Abbvie, Takeda, Ferring, Pfizer, Johnson and Johnson, Lilly, Galapagos, Celltrion, Arena, BMS, Falk, Biokuris, Fresenius-Kabi, Thabor Loftus, Jr, Edward: Grant: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Gilead, Janssen, Pfizer, Receptos, Robarts Clinical Trials, Takeda, Theravance, UCB. Personal Fees: AbbVie, Allergan, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, Iterative Scopes, Janssen, Ono Pharma, Pfizer, Sun Pharma, Takeda, UCB. Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Dubinsky, Marla C: Personal Fees: Consultant or Advisory Board: Abbvie, Abivax, Astra Zeneca, BMS, Celltrion, Gilead, Genentech, Janssen, Johnson and Johnson, Lilly, Merck, Pfizer, Prometheus Biosciences, Sanofi, Spyre, Target RWE, Takeda Other: Shareholder, Co-founder, Board of Directors of Trellus Health Co-Founder Mi Test Health Hisamatsu, Tadakazu: Grant support: Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Takeda, Pfizer., Mochida, Boston Scientific Corporation, Kissei Pharmaceutical Co. Ltd. Consulting: Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, Janssen Pharmaceutical K.K., Pfizer, Eli Lilly, Gilead Sciences, Bristol Myers Squibb, Abivax, MSD, Chugai. Lecture fee: Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda, Pfizer, Kissei Mambetsariev, Nurbek: Employee of AbbVie and may own stock and/or stock options. Kalabic, Jasmina: Employee of AbbVie and may own stock and/or stock options. Cheng, Peiyao: Employee of AbbVie and may own stock and/or stock options. Chen, Su: Employee of AbbVie and may own stock and/or stock options. O’Brien, Dan: Employee of AbbVie and may own stock and/or options. Morisset, Pierre: Employee of AbbVie and may own stock and/or stock options. Duan, W. Rachel: Employee of AbbVie and may own stock and/or stock options. Panaccione, Remo: Grant: Abbvie, Janssen, Pfizer, Takeda. Other: Consultant for: Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Spyre Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Union Biopharma, Viatris, Ventyx, UCB Speaker’s Fees for: AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda Pharmaceuticals Advisory Boards for: AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, SandozShire, Sublimity Therapeutics, Takeda Pharmaceuticals, Ventyx.