bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase III randomized, double-blinded, placebo-controlled study of suvemcitug combined with chemotherapy for platinum-resistant ovarian cancer (SCORES).
Authors: Yuan Guangwen , Wu Lingying , Li Qingshui , Lou Ge , Li Jundong , Liu Xiaowei , Wang Danbo , Yang Chen , Sun Shuguang , Zhang Jiajing 
Published: June 2024

LBA5516 Background: Suvemcitug is a new-generation recombinant humanized anti-VEGF rabbit monoclonal antibody. In the previous P1b study, Suvemcitug demonstrated its favorable safety profile and efficacy signals when combo with chemotherapy in platinum-resistant ovarian cancer (PROC). SCORES is the first randomized, double-blind, placebo-controlled phase III clinical trial to confirm the efficacy of Suvemcitug combo with chemo in PROC, whether or not previously received antiangiogenic agents or PARP inhibitors. Methods: Eligible patients had progressed during platinum-based therapy or within 6 months after ≥4 cycles of platinum-based therapy with at least one measurable lesion. After the investigators chose chemotherapy (CT) (weekly paclitaxel 80 mg/ m2 d1, 8, 15 & 22 q4w, pegylated liposomal doxorubicin 40 mg/m2 d1 q4w or topotecan 4 mg/m2 d1, 8 & 15 q4w), patients were randomly assigned (2:1) to either Suvemcitug (1.5 mg/kg q2w) or placebo combine with CT until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) by blinded independent review committee (BIRC) according to the RECIST 1.1. Key secondary end point is the overall survival (OS). Results: A total of 421 patients were enrolled between June 2021 and June 2023 in China. As the data cut off of the primary efficacy analysis (8 December 2023), 197 PFS events (70.1%) in Suvemcitug arm and 111 PFS events (79.3%) in placebo arm had occurred with the median follow-up of 14.36 and 14.26 months, respectively. The median PFS by BIRC was 5.49 months in Suvemcitug arm versus 2.73 months in placebo arm (hazard ratio[HR] 0.46, p<0.0001). OS data are immature. 42.7% and 50.7% of patients are deceased in Suvemcitug arm or placebo arm respectively, and there is a trend of OS benefit trend: median OS 16.07 months vs. 14.88 months, HR 0.79, p=0.1244. Efficacy results are summarized below. Treatment-emergent adverse events (TRAEs) occurred in all patients in Suvemcitug arm, with the most common being neutrophil count decreased, white blood cell count decreased and platelet count decreased. No Suvemcitug-related grade 5 TEAE occurred. Conclusions: To the best of our knowledge, this is the first double-blinded phase III study demonstrated promising antitumor activity of anti-angiogenic agent in patients with PROC. The improvement in PFS, ORR and DCR gained by adding Suvemcitug to single-agent CT was observed with no new safety concern. Clinical trial information: NCT04908787 . [Table: see text]
PRGN-2012, a novel gorilla adenovirus-based immunotherapy, provides the first treatment that leads to complete and durable responses in recurrent respiratory papillomatosis patients.
Authors: Norberg Scott , Gulley James L. , Schlom Jeffrey , Lankford Amy , Semnani Roshanak , Shah Rutul R. , Brough Douglas E , Sabzevari Helen , Allen Clint 
Published: June 2024

LBA6015 Background: Recurrent respiratory papillomatosis (RRP) is a rare, neoplastic disorder caused by chronic infection with human papillomavirus (HPV) type 6 or 11. Significant morbidity can occur due to airway obstruction and, although rare, transformation into malignant cancer. There are no approved therapeutics. RRP is currently managed with frequent ablative procedures that can lead to irreversible laryngotracheal scarring and disability. PRGN-2012 is a gorilla adenovirus-based gene therapy/immunotherapy designed to generate HPV6/11-specific T cell immunity. The FDA has granted PRGN-2012 Breakthrough Therapy Designation for the treatment of RRP recognizing that this single arm study can serve as pivotal to support a licensing application. Methods: This pivotal trial (NCT04724980) evaluates the safety and efficacy of PRGN-2012 in patients with RRP requiring a minimum of 3 surgeries in the 12 months prior to treatment. Eligible patients received 4 subcutaneous (SC) injections of PRGN-2012 at dose level (DL) 1 (1x1011 Particle Units (PU) per injection; n=3) or DL2 (5x1011 PU per injection; n=35) over 12 weeks. The primary endpoint was the rate of complete response (CR), defined as no requirement for surgery in the 12 months following completion of treatment. Other key endpoints include duration of response, change in extent of papilloma growth (anatomic Derkay score) and vocal function. Results: PRGN-2012 was well-tolerated, with no serious adverse events, grade > 2 treatment-related adverse events, or early treatment discontinuations. The most common adverse events were injection-site reaction, fatigue, chills, fever, and myalgia. PRGN-2012 treatment at DL2 significantly (p<0.0001) decreased the requirement for surgery, with a median number of surgeries in the 12 month period decreasing from 4 (3-10) prior to treatment to 0 (0-7) surgeries post-treatment. Approximately 90% of patients experienced a decrease in the number of surgeries in the 12 months post-treatment compared to pre-treatment with PRGN-2012. The primary endpoint evaluation demonstrated a confirmed complete response in 17/31 (55%) of evaluable patients. The median duration of complete response has yet to be reached with a median follow up of 15 months (12 - 30) at the time of data cutoff (March 6, 2024). Additionally, PRGN-2012 treatment resulted in a significant reduction in Derkay score, improvement in vocal function and generation of HPV-specific immune responses. Conclusions: These data demonstrate the overall favorable safety profile and significant clinical benefit of PRGN-2012 in adult RRP patients. These findings support PRGN-2012 as a potential therapeutic option for this patient population where no FDA-approved therapeutics exist. Clinical trial information: NCT04724980 .
Neoadjuvant nivolumab (NIVO) + chemotherapy (chemo) vs chemo in patients (pts) with resectable NSCLC: 4-year update from CheckMate 816.
Authors: Spicer Jonathan , Girard Nicolas , Provencio Mariano , Wang Changli , Mitsudomi Tetsuya , Awad Mark M. , Vokes Everett E. , Taube Janis M. , Lupinacci Lorena , Saylors Gene B. , Tanaka Fumihiro , Liberman Moishe , Lee Sung Yong , Alexandru Aurelia , D’Arcangelo Manolo , Tran Phuong , Mahmood Javed , Gharpure Vishwanath Suresh , Bhingare Apurva , Forde Patrick M. 
Published: June 2024

LBA8010 Background: The phase 3 CheckMate 816 study established neoadjuvant NIVO + chemo as a standard of care for eligible pts with resectable NSCLC. Here, we report the 4-year survival update from this study, representing the longest follow-up among all global phase 3 studies evaluating neoadjuvant or perioperative immunotherapy-based treatments. Methods: Adults with stage IB (≥ 4 cm)–IIIA (per AJCC v7) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR/ ALK alterations were randomized 1:1 to receive NIVO 360 mg + chemo Q3W or chemo alone Q3W for 3 cycles, followed by surgery. Event-free survival (EFS) and pathologic complete response (pCR; both per blinded independent review) were primary endpoints and were both statistically significant. Overall survival (OS) was a key secondary endpoint. Exploratory analyses included efficacy by pCR status and extent of resection. Results: At the 23 Feb 2024 database lock (median follow-up, 57.6 mo), NIVO + chemo continued to improve EFS vs chemo (median, 43.8 mo vs 18.4 mo; HR [95% CI], 0.66 [0.49–0.90]); 4-year EFS rates were 49% vs 38%. EFS favored NIVO + chemo vs chemo regardless of whether pts had lobectomy or pneumonectomy (Table), with 56%–57% vs 40%–43% of pts without disease recurrence at 4 years. NIVO + chemo also continued to show OS improvement vs chemo (HR [98.36% CI], 0.71 [0.47–1.07]; P = 0.0451; median OS was not reached [NR] in both arms, and the significance boundary was not met at this interim analysis). An OS improvement of 13% was sustained over time for NIVO + chemo vs chemo; 4-year OS rates were 71% vs 58%. Pts in the NIVO + chemo arm who had pCR continued to have improved OS vs those who did not (HR [95% CI], 0.08 [0.02–0.34]); 4-year OS rates, 95% vs 63%); a similar trend was seen in the chemo arm, although few pts had pCR with chemo (n = 4). No new safety signals were observed at this update. Additional survival analyses in pt subgroups and by ctDNA levels will be presented. Conclusions: In this 4-year analysis from CheckMate 816, neoadjuvant NIVO + chemo sustained EFS and OS separation vs chemo over time and demonstrated the long-term survival benefit of having pCR in pts with resectable NSCLC. These data provide the first understanding of the long-term benefits of neoadjuvant immunotherapy when added to chemo, reinforcing neoadjuvant NIVO + chemo as a standard of care, and providing a benchmark to assess the benefits of all perioperative immunotherapy-based treatments. Clinical trial information: NCT02998528 . [Table: see text]
IMpower010: Final disease-free survival (DFS) and second overall survival (OS) interim results after ≥5 years of follow up of a phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA non-small cell lung cancer (NSCLC).
Authors: Wakelee Heather A. , Altorki Nasser K. , Zhou Caicun , Csőszi Tibor , Vynnychenko Ihor O. , Goloborodko Oleksandr , Rittmeyer Achim , Reck Martin , Martinez-Marti Alex , Kenmotsu Hirotsugu , Chen Yuh-Min , Chella Antonio , Sugawara Shunichi , Fu Chenqi , Ballinger Marcus , Deng Yu , Srivastava Minu K , Bennett Elizabeth , Gitlitz Barbara Jenifer , Felip Enriqueta 
Published: June 2024

LBA8035 Background: IMpower010 (NCT02486718) met its primary endpoint of significant DFS improvement with atezo vs BSC after adj chemotherapy in resected NSCLC in the PD-L1 TC ≥1% and all-randomized stage II-IIIA populations, leading to worldwide approval of adj atezo for PD-L1 TC ≥1% or PD-L1 TC ≥50% stage II-IIIA NSCLC. At OS IA1, a trend favoring atezo was seen in the PD-L1 TC ≥1% stage II-IIIA population. Here we report findings from the DFS FA and OS IA2. Methods: The IMpower010 study design has been previously described (Felip et al, Lancet 2021). The primary DFS and secondary OS endpoints were tested hierarchically: DFS in the PD-L1 TC ≥1% (SP263) stage II-IIIA, then in the all-randomized stage II-IIIA, and then in the intent-to-treat (ITT; stage IB-IIIA) populations, followed by OS in the ITT population. Secondary endpoints included 3- and 5-y DFS and DFS in the PD-L1 TC ≥50% (SP263) stage II-IIIA population. OS in the ITT population could only be formally tested if the significance boundary for DFS in that population was crossed. Results: At the DFS FA and OS IA2 (clinical cutoff date: Jan 26, 2024), with a minimum follow-up of 60 mo, DFS and OS for the PD-L1 TC ≥1% and TC ≥50% stage II-IIIA populations were consistent with previously observed benefit; the difference in median (m) DFS between arms in the PD-L1 TC ≥1% population was 31.2 mo (Table). In the ITT population, the significance boundary for DFS was not crossed and OS was similar between arms, although data were immature. The safety profile of atezo was consistent with prior analyses. Conclusions: These results provide the first cancer immunotherapy data with ≥5 y of follow-up from a Phase III study in resectable NSCLC. Although the statistical boundary for the ITT population was not crossed, DFS benefit with adj atezo continues to translate into a positive OS trend vs BSC in the PD-L1 TC ≥1% and TC ≥50% stage II-IIIA populations. These results further support the use of adj atezo in PD-L1–selected populations. Clinical trial information: NCT02486718 . [Table: see text]
KROCUS: A phase II study investigating the efficacy and safety of fulzerasib (GFH925) in combination with cetuximab in patients with previously untreated advanced KRAS G12C mutated NSCLC.
Authors: Gregorc Vanesa , González-Cao Maria , Salvagni Stefania , Koumarianou Anna , Gil-Bazo Ignacio , Maio Michele , Viteri Santiago , Majem Margarita , Gutiérrez Vanesa , Bernabe Caro Reyes , Sanmamed Miguel F. , Zhu Huaqiang , Shen Haige , Wang Yu , Rosell Rafael 
Published: June 2024

LBA8511 Background: Fulzerasib (GFH925), a KRAS G12C inhibitor, showed substantial efficacy in previously treated NSCLC patients (pts) as monotherapy. Activation of epidermal growth factor receptor (EGFR) is identified to be one of the dominant mechanisms for KRAS inhibition resistance. Preclinical evidence showed synergistic activity in KRAS G12C mutant NSCLC modeling using fulzerasib in combination with cetuximab. Here we report the first results for a KRAS G12C inhibitor combined with an anti-EGFR antibody in NSCLC pts as front-line treatment. Methods: KROCUS (NCT05756153) was an open-label, single-arm, multi-center, Phase II study with the primary objective to evaluate the efficacy of fulzerasib in combination with cetuximab in pts with previously untreated advanced NSCLC harboring KRAS G12C mutation. Secondary objectives included safety/tolerability, pharmacokinetics and biomarkers. Pts were enrolled to receive fulzerasib (oral, 600 mg BID) and cetuximab (intravenous, 500 mg/m2, every two weeks [Q2W]) combination treatment in a 28-day cycle. Results: As of Jan. 30, 2024, a total of 27 pts (median age: 68 yrs old; 55.6% female) were treated, 11 (40.7%) with baseline brain metastases. Of 20 pts who had at least one post-treatment tumor assessment, ORR was 80.0% (95% CI: 56.3, 94.3, including one CR), of whom eight pts had ≥ 50% tumor shrinkages in the target lesions. Disease control rate (DCR) was 100% (95% CI: 83.2, 100.0). Five out of seven pts (71.4%) with brain metastases achieved PRs. Nine pts with baseline PD-L1 expression tested (six TPS≥1% and three TPS <1%) all achieved PRs. The overall safety profile of the combination was favorable. Treatment-related adverse events (TRAEs) of any grade occurred in 21 (77.8%) pts. 5 pts (18.5%) experienced G3 TRAEs and no G4 or 5 TRAEs. Three pts (11.1%) had dose reduction/interruption with fulzerasib due to TRAEs but no pts discontinued treatment while one pt (3.7%) had dose reduction/interruption and three (11.1%) discontinued cetuximab due to TRAEs. Table 1 shows the most common TRAEs or G3 TRAEs. Conclusions: The preliminary data from ongoing KROCUS study has demonstrated very promising efficacy and favorable safety profile of fulzerasib + cetuximab in the first line setting of KRAS G12C mutated NSCLC. More data will be generated to provide clinical evidence supporting this combination as a potential frontline therapy. Clinical trial information: NCT05756153 . [Table: see text]
Comparisons of Two-Stage Models for Flood Mitigation of Electrical Substations
Authors: Austgen Brent , Kutanoglu Erhan , Hasenbein John J. , Santoso Surya 
Published: June 2024

We compare stochastic programming and robust optimization decision models for informing the deployment of ad hoc flood mitigation measures to protect electrical substations prior to an imminent and uncertain hurricane. In our models, the first stage captures the deployment of a fixed quantity of flood mitigation resources, and the second stage captures the operation of a potentially degraded power grid with the primary goal of minimizing load shed. To model grid operation, we introduce adaptations of the direct current (DC) and linear programming alternating current (LPAC) power flow approximation models that feature relatively complete recourse by way of an indicator variable. We apply our models to a pair of geographically realistic flooding case studies, one based on Hurricane Harvey and the other on Tropical Storm Imelda. We investigate the effect of the mitigation budget, the choice of power flow model, and the uncertainty perspective on the optimal mitigation strategy. Our results indicate the mitigation budget and uncertainty perspective are impactful, whereas choosing between the DC and LPAC power flow models is of little to no consequence. To validate our models, we assess the performance of the mitigation solutions they prescribe in an alternating current (AC) power flow model. History: Accepted by Pascal Van Hentenryck, Area Editor for Computational Modeling: Methods & Analysis. Funding: This work was supported by the Energy Institute, The University of Texas at Austin. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2023.0125 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2023.0125 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .
Case Article—Budding with ERP: Information and Operations Management Challenges in a Nascent Industry
Authors: Jat Mohsin , Monette Jason , Kang Parminder Singh 
Published: June 2024

The role of analytics in operations and supply chain management (OSCM) has gained significant importance due to the decision-making complexities in the current business environment. The effectiveness of most analytical approaches, in turn, relies on access to timely and accurate data and information. Hence, it is essential for OSCM students to understand the underlying processes and dynamics of information management, for which enterprise resource planning (ERP) systems have become a standard. This case study can be a useful resource for introducing the critical interface between OSCM and information systems. The case study aims to facilitate learning on (1) the limitations of a rudimentary and disconnected information system, (2) the benefits and challenges of ERP implementation, and (3) the important steps to ensure a successful implementation of an ERP system. It provides an interesting context of a fast-growing agribusiness producing regulated products in Canada. The case study has been used in OSCM and management information systems (MIS) courses in two Canadian public Universities. Funding: This work was supported by Mitacs [Grants IT28747 and IT32722]. Supplemental Material: The Teaching Note and data files are available at https://www.informs.org/Publications/Subscribe/Access-Restricted-Materials .
The Operational Data Analytics (ODA) for Service Speed Design
Authors: Feng Qi , Jiang Zhibin , Liu Jue , Shanthikumar J. George , Yang Yang 
Published: June 2024

We develop the operational data analytics (ODA) framework for the classical service design problem of [Formula: see text] systems. The customer arrival rate is unknown. Instead, some historical data of interarrival times are collected. The data-integration model, specifying the mapping from the arrival data to the service rate, is formulated based on the time-scaling property of the stochastic service process. Validating the data-integration model against the long-run average service reward leads to a uniformly optimal service rate for any given sample size. We further derive the ODA-predicted reward function based on the data-integration model, which gives a consistent estimate of the underlying reward function. Our numerical experiments show that the ODA framework can lead to an efficient design of service rate and service capacity, which is insensitive to model specification. The ODA solution exhibits superior performance compared with the conventional estimation-and-then-optimization solutions in the small sample regime. This paper was accepted by David Simchi-Levi, operations management. Funding: Z. Jiang’s research is supported by the National Natural Science Foundation of China [Grant 71931007]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2023.00655 .
Number Processing Constraints and Earnings News
Authors: Karolyi Stephen , Ruchti Thomas , Truong Phong 
Published: June 2024

Neuroscience shows that human brains are neurologically constrained to process small numbers linearly and large numbers logarithmically, leading to underreactions to larger numbers as their perceived difference becomes smaller. We test this hypothesis in the context of earnings announcements and find that investors respond less in the short term to earnings news for stocks with high earnings per share magnitudes, exacerbating postearnings announcement drift for these stocks. These findings are distinct from and incremental to several risk-based and behavioral explanations, attenuated by robot presence and present in a quasi-experimental design using stock splits. Our evidence suggests that number processing constraints have implications for stock price efficiency. This paper was accepted by Will Cong, finance. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.01722 .
Immediate versus expedient emergent laparotomy in unstable isolated abdominal trauma patients
Authors: Maya P , Moran B , Khan M , Yehuda H , Adi G , Joseph DJ ,   Israeli Trauma Group, Boris K 
Published: June 2024

Introduction Unstable abdominal trauma patients should be treated with emergent laparotomy. However, few studies have evaluated the association between time to surgery and survival in these patients. We aimed to assess the influence of time to laparotomy on outcomes in blunt and penetrating unstable abdominal trauma patients. Methods This retrospective study includes patients with abdominal injuries, systolic blood pressure <90mmHg on arrival, admitted in Israel during 2000–2018. Data regarding patients’ characteristics, Injury Severity Score (ISS), Glasgow Coma Scale (GCS), time to surgery, length of hospital stay and mortality were collected via The Israeli National Trauma Registry. Results Overall, 69 blunt and 127 penetrating injury patients were included in the study. For blunt and penetrating trauma patients with ISS ≤14, no differences in outcome were found between patients who underwent laparotomy within 60min of admission and those who underwent laparotomy within 60–120min of admission. In patients with blunt trauma, ISS ≥16, and GCS <15, mortality was higher in the immediate laparotomy group (p = 0.004 and 0.049, respectively). Conclusions In patients with a penetrating injury, no differences in mortality between immediate and expedient laparotomy were demonstrated. In patients with a blunt injury, with ISS ≥16 and GCS <15, mortality was higher among the immediate laparotomy group.
Ultra-low loss Rayleigh scattering enhancement via light recycling in fiber cladding
Authors: Luo Pengtao , Chen Fengyi , Wang Ruohui , Qiao Xueguang 
Published: June 2024

Rayleigh backscattering enhancement (RSE) of optical fibers is an effective means to improve the performance of distributed optical fiber sensing. Femtosecond laser direct-writing techniques have been used to modulate the fiber core for RSE. However, in-core modulation loses more transmission light, thus limiting the sensing distance. In this work, a cladding-type RSE (cl-RSE) structure is proposed, where the femtosecond laser is focused in the fiber cladding and an array of scatterers is written parallel to the core. The refractive-index modulation structure redistributes the light in the cladding, and the backward scattered light is recovered, which enhances the Rayleigh backscattered signal with almost no effect on the core light. Experimentally, it was demonstrated that in an effectual cl-RSE structure, the insertion loss was reduced to 0.00001 dB per scatterer, corresponding to the lowest value for a point scatterer to date. The cl-RSE structure accomplished measurements up to 800°C. In particular, the temperature measurement fluctuation of the cl-RSE fiber portion is only 0.00273°C after annealing. These results show that the cl-RSE structure has effective scattering enhancement, ultra-low loss, and excellent high-temperature characteristics, and has great potential for application in Rayleigh scattering-enhanced distributed fiber sensing.