374 Background: CLDN18.2 is a therapeutic target on gastric, gastroesophageal, and esophageal adenocarcinomas (GC/GEJC/EC) with normal expression limited to the gastric epithelium. We present interim results of a dose-escalation trial of LB1908, a CLDN18.2-targeted autologous chimeric antigen receptor (CAR)-T cell product in adults with advanced GC/GEJC/EC. Methods: LB1908-1001 is an ongoing, multicenter, phase 1 study of LB1908 in subjects with advanced GC/GEJC/EC, relapsed or refractory to ≥1 prior line of therapy (LOT), with ≥1+ CLDN18.2 expression in ≥50% of tumor cells. A 3+3 design evaluated 3 dose levels (DLs): 0.5, 1.5, and 3 × 10 6 CAR-T cells/kg. Subjects receive a single infusion of LB1908 after standard lymphodepletion (LD). The primary objective is to evaluate safety and dose-limiting toxicities (DLTs). Results: As of 28 Aug 2025,13 subjects (median 56 yrs) received LB1908 (6 at DL1; 3 at DL2; 4 at DL3): 6 with EC, 4 GC, and 3 GEJC (median 2 prior LOTs, range 1–8). Median tumor CLDN18.2 expression was 95% and H-score was 245. Eleven subjects received bridging therapy between apheresis and LB1908 infusion. The most common grade ≥3 TEAEs were hematologic and attributed to the LD regimen. The only non-hematologic LB1908-related TEAEs grade ≥3 occurring in ≥2 subjects were gastritis (n=3) and gastric mucosal lesion (n=2), including 1 DLT at DL1. After this DLT mitigation guidelines were introduced (prophylactic enteral beclomethasone and moderate-dose systemic steroids). In the 6 subjects treated since implementing prophylaxis, no DLTs have been observed and upper GI toxicity has been manageable. Ten subjects (76.9%) experienced low-grade cytokine release syndrome (CRS; 4 grade 1 and 6 grade 2), at a median 6 days post-infusion. Four subjects received tocilizumab; no steroids were required to treat CRS. There were no cases of ICANS or TEAE-related deaths. CAR-T cells expanded in all subjects (median C max , 1594 and 2211 copies/µg genomic DNA; median T max , 14 and 20 days at DL1 and DL2, respectively). There was no clear dose-exposure relationship based on DL1 and DL2 data. Of 10 response-evaluable subjects, 9 (90%) had tumor shrinkage (5/6 at DL1, 3/3 at DL2, 1/1 at DL3). Three subjects had RECIST-defined partial responses (1 at each DL). At DL2, all 3 subjects achieved disease control, which correlated inversely with CD4:CD8 ratio in the drug product (R 2 =0.8). Six subjects maintained disease control ≥50 days, including >10 months in the subject with the longest follow up. Response and PK data from DL3 are incomplete as of the data cut. Conclusions: LB1908 demonstrated expansion and anti-tumor activity across DLs in heavily pretreated subjects with advanced GC/GEJC/EC. Prophylaxis with beclomethasone and systemic steroids reduced the on-target/off-tumor toxicity of gastritis/gastric mucosal injury. Dosing at DL3 is ongoing to determine the optimal dose for expansion. Clinical trial information: NCT05539430 .

822 Background: Assessing trial feasibility and predicting accrual is difficult and often inaccurate, resulting in the costly activation of studies that do not achieve their intended accrual. Artificial intelligence (AI) tools, including large language models (LLM), may complement expert judgment by systematically identifying trials with limited enrollment potential. The objective of this study was to compare investigator and LLM-based accrual estimates against actual accrual outcomes for gastrointestinal (GI) oncology trials. A secondary objective was to evaluate whether LLM-based accrual estimates could flag trials at risk of non-accrual. Methods: This study retrospectively examined GI oncology trials that closed before July 2024, prior to the adoption of the Triomics PRISM platform. For each trial, three measures were compared: investigator-derived accrual estimates generated before activation, actual patient accrual, and projections from OncoLLM (an LLM fine-tuned on institutional data and oncology guidelines). Accuracy was evaluated using two complementary approaches. First, the mean absolute error (MAE) was calculated between projected and actual accrual across trials. Second, a binary classification framework was applied using a pragmatic cutoff of ≤5 projected patients to flag trials at risk of non-accrual. Sensitivity, specificity, and overall accuracy were measured. Results: A total of 8 gastrointestinal oncology trials were included, with an average total accrual of 0.9 patients (SD 0.8). Investigator estimates were more accurate for continuous prediction (MAE 3.9 vs. 8.8 for OncoLLM). In the binary analysis, 4 of 8 trials (50%) closed with zero accrual. OncoLLM correctly classified 3 of the 4 trials as at risk of non-accrual (sensitivity 75%, specificity 100%). Across all 8 trials, OncoLLM correctly classified 7 (88%) as either at risk of non-accrual or not. Conclusions: While investigator estimates were closer to observed accrual when measured continuously, OncoLLM demonstrated value as a screening tool for identifying trials at risk of non-accrual. The model correctly classified 7 of 8 trials and flagged 3 of 4 non-accruing studies as at risk of non-accrual. LLM-based feasibility screening can be a complementary safeguard prior to trial activation, supporting more efficient resource allocation. Comparison of OncoLLM and physician estimates for trial accrual. Trial Physician Estimate OncoLLM Estimate Actual Accrual OncoLLM (At Risk of Non-Accrual) Actual No Accrual OncoLLM Correct 1 5 4 0 Yes Yes Yes 2 5 6 1 No No Yes 3 5 19 2 No No Yes 4 ≤5 0 0 Yes Yes Yes 5 5 26 2 No No Yes 6 4 3 0 Yes Yes Yes 7 5 9 0 No Yes No 8 5 10 2 No No Yes

4552 Background: Emerging evidence suggests that circadian rhythms may influence the efficacy of immune checkpoint inhibitors (ICIs) by modulating immune cell activity and T-cell trafficking. This study evaluated whether the timing of ICI administration (early vs. late) affects progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Methods: We conducted a single-center retrospective study of 97 patients with Stage IV mRCC treated with first-line ICIs. Patients were categorized by infusion timing: "Early" (n=68) vs. "Late" (n=29), with the cutoff defined by the median infusion time of 2:00 PM. Treatment regimens included ipilimumab/nivolumab (37%), nivolumab (36%), and pembrolizumab (27%); 23% received ICI in combination with a VEGF-targeted tyrosine kinase inhibitor. Outcomes were analyzed using Kaplan-Meier curves and multivariable Cox regression models, adjusting for age and International Metastatic RCC Database Consortium (IMDC) risk scores. Results: The median age was 65 years (IQR 59–71), 77% of patients were male, and 88% had clear cell histology. IMDC risk categories were intermediate (56%), poor (27%), and favorable (18%). At a median follow-up of 54.8 months, early infusion was associated with significantly improved OS (median 54 vs. 29 months; adjusted HR 1.79; 95% CI 1.02–3.12; p = 0.041) and PFS (median not reached; adjusted HR 3.59; 95% CI 1.27–10.20; p = 0.016) after adjustment for age and IMDC risk. Landmark 60-month OS was 40% vs. 31%, and PFS was 79% vs. 60% for the early vs. late groups, respectively. The incidence of any-grade immune-related adverse events (irAEs) was similar (54% in the early group vs. 52% in the late group), and poor IMDC risk remained a significant predictor of OS in the multivariable model (HR 3.09; 95% CI 1.22–7.8; p = 0.017). Conclusions: In this mRCC cohort, ICI administration before 2:00 PM was associated with significant improvements in both PFS and OS, including a nearly two-fold increase in median overall survival compared to late-afternoon administration. These findings are hypothesis-generating and suggest that the timing of immunotherapy may be an immediately actionable, high-impact variable in optimizing mRCC treatment. Prospective validation is warranted.

e16445 Background: Clinical trials serve as a critical pathway to novel, potentially life-saving treatments and provide structured care, rigorous monitoring, and additional resources for patients undergoing cancer treatments. We hypothesize that clinical trial enrollment may improve survival outcomes by standardizing therapy and ensuring equitable follow-up. This study aims to evaluate whether participation in a clinical trial enhances survival for patients with pancreas cancer (PC) and closes the survival gap between Black and White patients. Methods: This is a retrospective analysis of a prospectively maintained database of patients with PC at a single high-volume tertiary referral center. The study was approved by the institutional IRB. Patients with biopsy-proven resectable (R) or borderline resectable (BLR) PC who were diagnosed between 2014-2023 and received neoadjuvant therapy (NeoTx) were included. The cohort was divided into two groups: patients enrolled in ≥ 1 clinical trials (Trial) vs. not enrolled (NoTrial). Results: 634 consecutive patients were included: 266 (42%) with R-PC and 368 (58%) with BLR-PC. Median age was 67 yrs (IQR 13), 281 (44%) patients were female, and 571 (90%) were White. Of the 634 patients, 414 (65%) were in the NoTrial group and 220 (35%) in the Trial group. All patients received NeoTx; 93 (15%) received chemoradiation alone, 61 (9%) received chemotherapy alone, and 480 (76%) received both. Patients enrolled in a clinical trial were twice as likely to complete neoadjuvant therapy and surgery with an OR: 2.18, 95%CI [1.41 – 3.38], p < 0.001, after controlling for variables associated with trial enrollment, including age, race, comorbidities, area deprivation index, radiographic stage at diagnosis, and type of NeoTx.In contrast, patients with multiple comorbidities or BLR-PC had decreased odds of completing all intended therapies with OR:0.58, 95%CI [0.37 – 0.90], p = 0.02 and OR:0.34, 95%CI [0.22 – 0.52], p < 0.001 respectively. Median overall survival (mOS) for all 634 patients was 28 months; 41 months for the 435 (69%) who completed all intended NeoTx and surgery. mOS was significantly longer in Trial vs. NoTrial; 33 months vs. 26 months, p = 0.006. mOS for White, Trial vs. NoTrial patients was 34 months vs. 26 months, p = 0.006. There was a trend towards improved survival in Black Trial vs. NoTrial patients (24 months vs. 18 months, p = 0.27). Conclusions: Enrollment in clinical trials significantly improved completion rates of neoadjuvant therapy and surgery and was associated with improved survival outcomes in patients with R-PC and BLR-PC. Our data provides a signal that clinical trial enrollment may ameliorate disparities in PC survival outcomes in minorized patient populations. Demographics summary and pretreatment disease characteristics. No trial(n=414) Trial(n=220) All(n=634) p-value Age, median (IQR) 68 (14) 65 (13) 67 (13) <0.001 Gender, n (%) Female Male 188 (45)226 (55) 93 (42)127 (58) 281 (44)353 (56) 0.449 Race, n (%) White Black Other/Unknown 382 (92)22 (5)10 (3) 189 (86)18 (8)13 (6) 571 (90)40 (6)23 (4) 0.025 Area Deprivation Index, n (%) <50 >50 252 (63)149 (37) 143 (67)71 (33) 395 (64)220 (36) 0.327 BMI (kg/m 2 ), median (IQR) 27.0 (6.5) 28.2 (6.9) 27.3 (6.9) 0.009 Age adjusted Charlson Comorbidity Index, mean (SD) 5.6 (2.2) 4.8 (1.4) 5.3 (2.0) <0.001 CA19-9 at diagnosis (U/ml), median (IQR) 74 (407) 125 (427) 92 (407) 0.070 Clinical and radiographic stage at diagnosis, n (%) Resectable Borderline 159 (38)255 (62) 107 (49)113 (51) 266 (42)368 (58) 0.013 Neoadjuvant treatment, n (%) Chemoradiation alone Chemotherapy alone Both 72 (18)30 (7)312 (75) 21 (10)31 (14)168 (76) 93 (15)61 (9)480 (76) 0.001

BACKGROUND:Controversy exists regarding the benefit of lymphadenectomy for nonfunctional pancreatic neuroendocrine tumors (NF-PNET). PATIENTS AND METHODS:MEDLINE/PubMed, EMBASE, and the Cochrane Library were searched for studies of pancreatic neuroendocrine tumors (PNET) published between 1990 and 2021. Studies of functional PNET were excluded. Reported incidence of lymph node metastasis (LNM) and survival analysis of either disease-free survival (DFS) or overall survival (OS) were required for inclusion. RESULTS:Overall, 52 studies analyzing 24,608 PNET met the inclusion criteria. The reported LNM rate for NF-PNET ranged from 7 to 64 % (median 24.5%). Reported LNM rates ranged from 7 to 51% (median 11%) for NF-PNET< 2 cm in 14 studies and 29-47% (median 38%) in NF-PNET > 2 cm. In total, 19 studies (66%) reported LNM to have a negative impact on DFS. Additionally, 21 studies (60%) reported LNM to have a negative impact on OS. Two studies investigating the impact of lymphadenectomy (LND) found LND had the greatest impact for large, high-grade tumors. The overall quality of available evidence was low as assessed by the Grading of Recommendations, Assessment, Development, and Evaluation System. CONCLUSIONS:Published literature evaluating the impact of regional LNM and LND in PNET is confounded by heterogeneity in practice patterns and the retrospective nature of these cohort studies. Most studies suggest high rates of LNM in NF-PNET that negatively impact DFS and OS. Given the high rate of LNM in NF-PNET and its potential detrimental effect on DFS and OS, we recommend lymphadenectomy be completed for NF-PNET > 2 cm and strongly considered for NF-PNET < 2 cm.

Purpose: Conditions for which neuroendocrine tumor (NET) is commonly misdiagnosed were compared among patients with and without NET, and the associated healthcare costs were described. Methods: Adults with a NET diagnosis were selected retrospectively from the IBM MarketScan claims databases during 1/1/2015-12/31/2018 (earliest = index), comprising the NET cases. Non-NET controls included age/ gender matched patients without any cancer diagnoses. Patients were followed for a five year look back period when conditions for which NET is commonly misdiagnosed (gastrointestinal, respiratory, metabolic [i.e. liver disease], dermatologic) were measured and compared between cases and matched controls using odds ratios. Misdiagnosis-related costs were reported per patient per month (PPPM) from the earliest misdiagnosis to NET diagnosis. Patients with pancreatic adenocarcinoma misdiagnoses and related costs were reported separately. Results: This analysis included 3460 NET cases and 10,370 non-NET controls (mean age 61 years). Compared to non-NET controls, 70 % of NET cases had a diagnosis of a gastrointestinal, respiratory, metabolic, or dermatologic condition, with 2.07 higher odds (95 % CI 1.91-2.25). Median time from earliest potential misdiagnosis to NET was 3.4 years. Overall mean (standard deviation) healthcare costs related to misdiagnoses were $2858 ($6495) PPPM. Costs were highest for gastrointestinal misdiagnoses ($3350 [$7108]). Among NET cases, 69 (2 %) patients had a pancreatic adenocarcinoma misdiagnosis; related PPPM costs were substantial ($29,321 [$62,385]) and driven by outpatient services including treatment administration. Conclusion: The increased odds of common misdiagnosis conditions among NET cases compared with non-NET controls, contributing to unnecessary healthcare costs, supports the need for accurate identification of NET. Synopsis: The majority of patients with NET (70 %) were previously misdiagnosed, occurring a median of 3.4 years before correct diagnosis. Total mean healthcare costs related to misdiagnoses were $2858 PPPM and costs related to pancreatic adenocarcinoma misdiagnoses were substantial ($29,321 PPPM).

PDF file,76K, Details of pNets studied

Abstract The success of drugs targeting angiogenesis is tempered by the transient duration of disease control and modest survival improvement. The very hypoxic stress produced by successful therapy may lead to upregulation of multiple pathways that promote angiogenesis and invasive behavior. Overcoming this evasive resistance may further improve outcome. Clin Cancer Res; 17(16); 5217–9. ©2011 AACR.

Background: Long-acting somatostatin analog therapy (LA-SSA) is recommended as first-line therapy for treatment of unresectable or metastatic neuroendocrine tumors (NETs). Understanding treatment sequencing and dosing patterns of LA-SSA is essential for clinical decision-making to provide value-based management of NETs. Objective: To describe treatment patterns of LA-SSA among patients with NETs and subgroups with carcinoid syndrome (CS) in the United States. Methods: This retrospective study utilized claims data from MarketScan® databases to identify patients with NETs and newly treated with LA-SSA between January 1, 2015, and October 31, 2020. Patients were stratified by index LA-SSA (lanreotide and octreotide long-acting release [LAR]). Reported 28-day doses were based on claim fields for days' supply/drug quantity or units of service. Dose escalation was defined as increases in quantity or frequency. Continuous variables, categorical variables, and Kaplan-Meier estimated treatment durations were compared using t-tests, chi-square/Fisher's tests, and log-rank tests, respectively. Results: The study included 241 lanreotide and 521 octreotide LAR patients. Compared with octreotide LAR patients, treatment duration was longer for lanreotide patients (median, 41.3 vs 26.8 months; log-rank p=.004). Fewer lanreotide patients received rescue treatment with short-acting octreotide (7.9% vs 14.4%; p=.011), and a first (6.2% vs 27.3%) and second dose escalation (0.8% vs 5.2%; both p<.05). Among patients with doses reported, fewer lanreotide patients received above-label doses (2.5% [5/202] vs 14.4% [60/416]; p<.001). Among patients who ended treatment during follow-up, fewer lanreotide patients transitioned to another LA-SSA (18.9% [17/90] vs 33.6% [92/274]; p=.008). Similar treatment patterns were observed in CS subgroups. Results for switched treatment patterns were limited due to insufficient sample sizes. Discussion: Real-world treatment patterns of LA-SSA were assessed using more recent administrative claims data. Compared with octreotide LAR patients, lanreotide patients were more likely to remain longer on initial treatment and starting dose without dose escalations and less likely to use rescue treatment and transition to another LA-SSA after discontinuation of the index treatment. Conclusions: Findings from this claims study suggest a potential clinical benefit of lanreotide in NET management.

Related Article from Overcoming Antiangiogenic Resistance

PDF file - 506KB, Supp. Fig. S1 2D structures of Amoxapine, Amoxapine's metabolites, Loxapine, and the previous reported potent GUS inhibitors - Inhibitor 1 and 2. Suppl. Fig. S2 The initial structures (left panel, Before MD) and the last snapshots (right panel, After MD) taken from 4 ns MD simulation. Supp. Table S1. Hydrogen bonds formed by ligand and protein during the last 2 ns simulation. Supp. Table. S2 Histologic score and Ki-67-positive cells of the examined tissue.

Purpose of Review The field of neuroendocrine oncology has changed much since the time of Oberndorfer first described and coined the term carcinoid. The purpose of this review is to summarize recent findings and highlight clinically relevant updates in the management of NENs, particularly those that are practice changing. Recent Findings Neuroendocrine tumors (NETs) have replaced carcinoid tumor, for the most part. The classification of neuroendocrine neoplasms (NENs) improved, and the epidemiological understanding of this disease group also expanded with global collaborations and maturation of large tumor registries. Clarity in the utility of some NET biomarkers continues to be evolving. Knowledge of molecular drivers of tumorigenesis increases, and scientific/technological advancements lead the way to multiple drug approvals for the treatment of advanced NETs. The incidence and prevalence of NENs continue to increase, and patients are living longer. Better understanding of molecular drivers and further understanding of the role of immunotherapy in NENs will further elevate the level of care and transform care for all patients with NENs.

Neuroendocrine tumors (NETs) negatively impact patients’ quality of life. Octreotide long-acting release (LAR) and lanreotide depot are somatostatin analogs (SSAs) approved to treat NETs. The study objective was to explore SSA treatment experiences and preferences of patients with NETs. Qualitative interviews were conducted in US adults (≥ 21 years) with NETs who had ≥ 6 months’ treatment with each SSA and transitioned from octreotide LAR to lanreotide depot within the previous year. Participants were asked open-ended questions about their experiences with octreotide LAR and lanreotide depot, treatment preferences, and SSA treatment attributes. Twenty participants (mean age: 58 years; 90% female; 85% white) completed interviews. The most common reasons for treatment transition were doctor recommendation (70%), treatment not working as expected (55%), and injection type preference (45%). Participants reported 34 unique favorable attributes of SSA treatment and 82 unique unfavorable attributes. Symptom control was the most frequently reported favorable attribute (associated with octreotide LAR by 60% of participants and lanreotide depot by 65%). Painful injection (65%) was most frequently cited unfavorable attribute for octreotide LAR and injection experience dependent on administrator (35%) for lanreotide depot. The three SSA treatment attributes rated as most important were side effects, symptom control, and ability to stabilize tumor. Our qualitative data provide valuable insight into the treatment attributes that patients with NETs consider important when making SSA treatment decisions. Factors related to injection administration, side effects, and symptom control are important to patients and should be included in patient-provider communications in clinical contexts.