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MOONRAY-01, a phase 1 study of LY3962673, a potent, orally bioavailable, and selective KRAS G12D inhibitor in <i>KRAS G12D</i> -mutant solid tumors.

TPS845 Background: KRAS G12D mutations occur in ~35%, 13%, and 4% of pancreatic, colorectal, and non-small cell lung cancers, respectively and less commonly in other cancers. Currently, there are no approved therapies for patients with KRAS G12D -mutant solid tumors. LY3962673 is a potent and orally bioavailable inhibitor of GDP-bound KRAS G12D that is highly selective for KRAS G12D against wild-type KRAS and other RAS mutations or amplifications. Preclinically, LY3962673 demonstrated robust anti-tumor activity in vivo as a single-agent and in combination with other agents in multiple KRAS G12D PDX models (Gong X, et al. Poster presented at AACR 2024). Methods: MOONRAY-01 is a global, open-label, multicenter, first-in-human phase 1 study of oral LY3962673 in participants (pts) with KRAS G12D -mutant solid tumors conducted in 2 phases: phase 1a dose escalation (Part A) to evaluate LY3962673 monotherapy and phase 1b dose expansion/randomized dose optimization (Parts B-E) to evaluate LY3962673 monotherapy and in combination with other anticancer therapies (Table). In phase 1a, additional pts will be allowed to backfill to previously cleared dose levels that demonstrate therapeutically relevant exposures or direct evidence of clinical activity. In phase 1b, each combination cohort will include a safety lead-in of 3-6 pts. Phase 1a/b escalation will utilize the mTPI-2 method. The DLT evaluation period will be 28 days. Eligible pts (≥18 years) must have locally advanced, unresectable, and/or metastatic cancer, measurable disease per RECIST v1.1, evidence of KRAS G12D mutation in tumors or ctDNA, and an ECOG PS of 0-1; asymptomatic CNS disease is allowed. In phase 1a, pts must have received ≥1 prior line of systemic chemotherapy for advanced or metastatic disease. In phase 1b, prior KRAS therapy is not allowed; other eligibility requirements are outlined in the Table. Key exclusion criteria include known active CNS metastases and/or carcinomatous meningitis, or significant cardiovascular disease. Key objectives are to determine the RP2D/optimal dose and assess the safety, tolerability, PK properties, and antitumor activity of LY3962673 per RECIST v1.1. The study is currently enrolling pts. Clinical trial information: NCT06586515 . Phase 1b Parts Key Eligibility Cohorts B: PDAC · B1: ≥1 prior systemic therapy· B2, B3, B4: treatment naïve allowed· B5: treatment naïve only · *B1: LY3962673· B2: LY3962673 + gemcitabine (G) + nab-paclitaxel (P)· *B3: LY3962673 + G + P· B4: LY3962673 + mFOLFIRINOX· *B5: LY3962673 + mFOLFIRINOX C: CRC · C1, C2: ≥1 prior systemic therapy· C3, C4, C5: treatment naïve allowed · C1: LY3962673 + cetuximab (C)· *C2: LY3962673 + C· C3: LY3962673 + C + FOLFOX· C4: LY3962673 + C + FOLFIRI· *C5: LY3962673 + C + FOLFIRI / FOLFOX D: NSCLC · ≥1 prior systemic therapy · *D1: LY3962673 E: Other solid tumors · ≥1 prior systemic therapy · E1: LY3962673 * Cohorts randomized to various LY3962673 doses.

The Gastric Cancer Registry: A multi-omic cellular and molecular resource for cancer biomarker and therapeutic discovery.

491 Background: The Gastric Cancer Registry (GCR) is a comprehensive clinical and genomic data resource focused on gastric cancer (GC) patients and individuals with a family history of GC or a germline CDH1 mutation. As part of the GCR’s ongoing enrollment, patients contribute cancer history information, archival tumor samples and other biospecimens. The cancer samples undergo extensive molecular and cellular analysis that includes genomic sequencing and spatial analysis. We have generated a robust dataset, publicly accessible online through the GCR Genome Explorer (GCR-GE). This genomic, molecular and cellular resource provides a rich data set that accelerates multidisciplinary research aimed at improving detection and treatment strategies for GC. GC disproportionately affects Latin American populations - we have included new cohorts from Latin America. The GCR enables researchers, clinicians and patients to address specific questions about the molecular and cellular basis of GC. Methods: GC samples underwent whole genome, whole exome, and bulk RNA sequencing were conducted. The genomic features identified include copy number variation, gene mutations, gene expression, microbiome composition, estimation of tumor-infiltrating immune cells, tumor neoantigens, MSI/MSS status, and HLA subtypes. In addition to genomic data, clinical data was compiled from survey responses and pathology reports and integrated into the GCR-GE. We have incorporated single cell and spatial analysis that includes diverse cell types, single cell gene expression and cellular architecture in native tumor tissues. This data was released to the GCR Genome Explorer website. Results: A total of 817 subjects have enrolled in the GCR including 598 diagnosed with GC and 219 at high-risk for GC through family history of GC and/or a CDH1 mutation. Of the 598 with GC, some met multiple criteria including at least 40 with a family history of GC, 10 with a CDH1 mutation, and 18 with both a family history of GC and a CDH1 mutation. The GCR-GE includes data from 257 gastric tumors in addition to external datasets from TCGA. In the latest data release, clinical and genomic data from 78 gastric tumors from patients in Latin America were integrated into the GCR-GE. Conclusions: The GCR is a comprehensive database of crucial clinical and genomic data necessary for driving forward GC research. Through global expansion, the GCR has generated a more representative dataset by increasing racial diversity and including underrepresented populations that are at higher risk for GC.

Adding blinatumomab to chemotherapy reduces recurrence risk in standard-risk paediatric B-ALL

Molecular Imaging of Ovarian Follicles and Tumors With Near‐Infrared II Bioconjugates (Adv. Mater. 7/2025)

Colloid‐Forming Prodrug‐Hydrogel Composite Prolongs Lower Intraocular Pressure in Rodent Eyes after Subconjunctival Injection

Abstract Colloidal drug aggregates (CDAs) are challenging in drug discovery due to their unpredictable formation and interference with screening assays. These limitations are turned into a strategic advantage by leveraging CDAs as a drug delivery platform. This study explores the deliberate formation and stabilization of CDAs for local ocular drug delivery, using a modified smallmolecule glaucoma drug. A series of timolol prodrugs are synthesized and self‐assembled into CDAs. Of four prodrugs, timolol palmitate CDAs have a critical aggregate concentration of 2.72 µM and sustained in vitro release over 28 d. Timolol palmitate CDAs are dispersed throughout in situ gelling hyaluronan‐oxime hydrogel and injected into the subconjunctival space of rat eyes. The intraocular pressure is significantly reduced for at least 49 d with a single subconjunctival injection of timolol‐palmitate CDAs compared to 6 h for conventional timolol maleate. The systemic blood concentrations of timolol are significantly lower, even after 6 h, for timolol palmitate CDA‐loaded hydrogel versus free timolol maleate, thereby potentially reducing the risk of systemic side effects. This innovative approach redefines the role of CDAs and provides a framework for long‐acting ocular therapeutics, shifting their perception from a drug screening challenge to a powerful tool for sustained local drug delivery.

Prognostic and predictive role of circulating tumor DNA (ctDNA) in stage III colon cancer treated with celecoxib: Findings from CALGB (Alliance)/SWOG 80702.

LBA14 Background: CALGB/SWOG 80702 previously showed that the addition of celecoxib to standard adjuvant chemotherapy with FOLFOX did not significantly improve disease-free survival (DFS) in patients with stage III colon cancer. Here, we evaluated the prognostic and predictive value of ctDNA in identifying a subpopulation of patients who may benefit from celecoxib. Methods: In the subset of patients with adequate biospecimens who participated in CALGB/SWOG 80702, a randomized phase III trial of 3 versus 6 months of adjuvant 5-FU, leucovorin, oxaliplatin (FOLFOX) +/- celecoxib, ctDNA assessment was performed using a clinically validated, tumor-informed 16-plex mPCR-NGS assay (Signatera(TM), Natera, Inc.) after surgery and before the start of adjuvant therapy (baseline). The Kaplan-Meier method was used to describe the distribution of survival time based on ctDNA positivity and log-rank testing was performed. Cox proportional hazards models were used to examine unadjusted associations between ctDNA positivity and disease-free (DFS) and overall survival (OS). Two-sided P values equal to or less than 0.05 were considered statistically significant, except for interaction P values (tested with a likelihood ratio). Results: In total, 1,011 of the 2,526 patients who participated in 80702 had ctDNA testing results from baseline; 189 were ctDNA positive (18.7%). ctDNA positivity associated with male sex, higher T stage, and N2 (versus N1) stage. ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR] 6.52 [95% confident interval (CI) 5.09-8.34; p&lt;0.0001] and OS (HR 6.28 [95% CI 4.63-8.51; p&lt;0.0001]). Three-year DFS was 86.6% in ctDNA-negative cases and 36.8% in ctDNA-positive cases. Among patients who were ctDNA negative, celecoxib use was not significantly associated with worse DFS as compared to placebo (HR 0.75 [95% CI 0.54-1.05; p=0.095]) with a three-year DFS of 87.7% versus 85.5%, respectively. Among ctDNA-positive patients, celecoxib significantly improved DFS compared to placebo (HR 0.59 [95% CI 0.42-0.85; p=0.004]) with a three-year DFS of 44.1% versus 26.6% (P interaction = 0.25). Similar results were seen for overall survival with a hazard ratio of 0.86 (95% CI 0.56-1.33; p=0.49) for ctDNA negative cases and 0.63 (95% CI 0.41-0.96; p=0.028) for ctDNA-positive cases for celecoxib versus placebo (P interaction = 0.28). Conclusion: In a randomized phase III adjuvant therapy trial for stage III colon cancer, ctDNA was highly prognostic of DFS and OS. ctDNA positivity also appeared predictive of the benefit of adjuvant celecoxib for DFS and OS. These results suggest a potential role for ctDNA in determining which patients should consider celecoxib in addition to standard FOLFOX adjuvant therapy. Clinical trial information: NCT01150045 .

A phase I trial of intraperitoneal (IP) mesothelin (MSLN)-targeted CAR T-cell therapy in patients with MSLN-positive esophagogastric cancer (EGC) with peritoneal carcinomatosis.

TPS513 Background: Outcomes for patients with advanced EGC remain poor. The peritoneum is an immune-privileged niche and a common site of metastases occurring in up to 40% of patients with metastatic EGC; this is characterised by poor survival because of resistance to immunotherapy and a lack of measurable disease, which excludes trial participation. MSLN was selected as a target for CAR T cell therapy as it is overexpressed in up to 60% of EGC, is associated with aggressive disease biology and has low levels of expression in normal tissues. In pre-clinical in vivo models of peritoneal carcinomatosis, improved efficacy was observed with regional administration of IP CAR T cells, compared with systemic CAR T cells. No significant toxicity was observed at clinically relevant doses of IP administered CAR T-cells. M28z1XXPD1DNR CAR T-cells are a next-generation MSLN-targeted CAR, equipped with a modified CD3z (1XX), and a PD-1 dominant negative receptor (PD1DNR) that provides T-cell intrinsic checkpoint blockade. Methods: This is a single-arm phase I study assessing the safety, maximum tolerated dose (MTD) and preliminary efficacy of IP administered M28zXXPD1DNR CAR T cells in patients with MSLN-positive (IHC ≥ 25%) EGC with evidence of peritoneal carcinomatosis (imaging and/or cytology). Patients with concomitant extraperitoneal disease are eligible. Patients must have received at least one prior line of treatment for advanced or metastatic disease and have at least one measurable or evaluable lesion per RECIST 1.1. A minimum of 4 patients and maximum of 18 patients will be treated with 4 escalating doses (with 1 “fallback” dose) of CAR T cells to a maximum of 3 x 10 7 cells/kg administered via peritoneal catheter (Table). Lymphodepletion with fludarabine 30mg/m 2 /day and cyclophosphamide 300mg/m 2 /day is given for 3 days prior to the CAR T cell infusion. Adverse events, response rates (RECIST 1.1), survival outcomes and immuno-monitoring (immune cell phenotyping and serum/peritoneal fluid cytokine analysis) will be assessed. The trial is currently enrolling patients. Clinical trial information: Will be registered before ASCO GI. Dose-escalation scheme based on the continuous reassessment method. Dose Level Dose (cells/kg) 1 1 x 10 6 2 (Starting dose) 3 x 10 6 3 6 x 10 6 4 1 x 10 7 5 3 x 10 7

Perioperative chemoimmunotherapy for patients with gastric or gastroesophageal junction cancer: A systematic review and meta-analysis.

430 Background: Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis, in combination with chemotherapy, are known to improve survival in advanced/metastatic gastric (GC) or gastroesophageal junction cancer (GEJC). Therefore, several trials incorporated ICIs in the neoadjuvant/peri-operative setting with promising preliminary results. The purpose of this meta-analysis was to determine the safety and efficacy of neoadjuvant chemoimmunotherapy for resectable GC or GEJC. Methods: PubMed/MEDLINE and Embase were systematically searched for randomized control trials (RCTs) investigating the efficacy of neoadjuvant anti PD-1/PD-L1 ICIs for locally advanced GC or GEJC up to 07/27/2024. Outcomes of interest were surgical outcomes such as pathological complete response (pCR) rate and major pathological response (MPR) rate. Risk ratio (RR) with 95% confidence intervals (CI) were pooled using a fixed model meta-analysis. Statistical analysis was performed with Review Manager 5.4.1. I² statistics was used to assess heterogeneity. The Cochrane risk of bias assessment tool was used to assess the risk of bias. All analyses were conducted at a significance level of 0.05. Results: Seven RCTs comprising 2,911 GC or GEJC patients were included. Among these, 1,454 patients received neoadjuvant chemoimmunotherapy and 1,457 patients received chemotherapy, respectively. Neoadjuvant chemoimmunotherapy significantly improved pCR rate (RR 2.94; 95% CI 2.34-3.70; P&lt;0.00001; I 2 =33%), and MPR rate (RR 1.47; 95% CI 1.25-1.72; P&lt;0.00001; I 2 =30%) compared to chemotherapy alone. Chemoimmunotherapy was associated with slightly higher incidence of grade 3 or worse treatment-related adverse events than chemotherapy (RR 1.07; 95% CI 1.01-1.14; p=0.03; I 2 =0%). Conclusions: This meta-analysis showed that adding ICIs to chemotherapy significantly improved the pCR and MPR rates and was feasible for patients with locally advanced GC or GEJC. Results of survival outcomes in the included trials and ongoing trials are awaited to further determine the efficacy and utility of chemoimmunotherapy and identify patient populations that benefit from this strategy. Included studies. Author Year Trial# Design Cancer; Stage Name of IO Target Chemo regimen Extracted data pCR MPR TRAE Ding X 2023 NCT04982939 P2 G/GEJ; Stage2-3 Sintilimab PD-1 SOX ○ ○ 　 Janjigian YY 2023 NCT04592913 P3 G/GEJ; ≥T2Nany/T0-4 N+ Durvalumab PD-L1 FLOT ○ 　 ○ Li C 2023 NCT04208347 P3 G/GEJ; T3-4aN+ Camrelizumab PD-1 SOX(+apatinib) ○ ○ 　 Lin JX 2024 NCT04195828 P2 G; T2-4N+ Camrelizumab PD-1 S-1+nabPTX ○ ○ ○ Lorenzen S 2024 NCT03421288 P2 G/GEJ; ≥T2 and/or N1 Atezolizumab PD-L1 FLOT ○ ○ 　 Peng Z 2024 NCT04661150 P2 G/GEJ HER2+; resectable Atezolizumab PD-L1 CAPOX+Tmab ○ 　 　 Shitara K 2024 NCT03221426 P3 G/GEJ; ≥T3N+ Pembrolizumab PD-1 FLOT or XP/FP ○ 　 ○ Yuan SQ 2024 NCT04250948 P2 G/GEJ; T3-4N+ Toripalimab PD-1 SOX/CAPOX ○ ○ ○

Ipilimumab plus nivolumab efficacious in patients with dMMR/MSI-H disease

Scalable Multistep Roll‐to‐Roll Printing of Multifunctional and Robust Reentrant Microcavity Surfaces via a Wetting‐Induced Process (Adv. Mater. 5/2025)

Concurrent transarterial chemoembolization plus atezolizumab and bevacizumab in unresectable hepatocellular carcinoma: Interim analysis from a multicenter real-world study (CHANCE 023).

542 Background: Combining transarterial chemoembolization (TACE) with systemic therapies such as atezolizumab and bevacizumab (T+A) has shown potential efficacy in patients with unresectable Hepatocellular carcinoma (HCC) This interim analysis aims to evaluate the efficacy and safety of this combination therapy when administered concurrently within a two-month period. Methods: This multicenter, real-world study included patients diagnosed with unresectable HCC who received TACE combined with T+A from January 2020 to June 2024, across 37 centers in mainland China. The primary endpoint was overall survival (OS). This trial is registered with ClinicalTrials.gov, NCT06024252. Results: Out of a cohort of 335 patients, 293 (259 males) met the inclusion criteria, and 37.5% (112/293) adopted this regimen as second-line therapy. The interim analysis showed a median OS of 29.97 months and a one-year survival rate of 76.50%. The median PFS was 19.23 months, and the objective response rate (ORR) was 41.6%, with 26 complete responses and 96 partial responses. The disease control rate (DCR) was 84.6%. Common adverse events included bone marrow suppression, decreased white blood cell or platelet counts, among others. Serious adverse events occurred in 9.2% of patients (27/293) and were manageable with standard interventions. Conclusions: This study is a real-world analysis to highlight the potential benefits of combining TACE with T+A in this patient population. However, longer follow-up is required to better assess both overall survival and the long-term safety profile of this treatment strategy. Clinical trial information: NCT06024252 .

Paclitaxel oral solution versus paclitaxel injection as a second-line therapy in advanced gastric cancer: A randomized, open-label, non-inferiority phase 3 trial.

442 Background: Paclitaxel injection (paclitaxel IV) is category 1 preferred regimen in the second-line therapy of gastric cancer, while it has shortcomings including vehicle-led safety risk, long time injection, premedication or frequent hospital visit. Paclitaxel oral solution (Liporaxel), the world's first successfully developed oral formulation, is an alternative. This study aimed to establish non-inferiority in efficacy and comparable safety profile of paclitaxel oral solution versus paclitaxel IV, as a second-line monotherapy in gastric cancer. Methods: This is a randomized, open-label, non-inferiority phase 3 trial conducted at 53 centers in China. Patients with unresectable or recurrent or metastatic gastric cancer progressed after fluoropyrimidine- or fluoropyrimidine plus platinum-based first-line therapy were randomly assigned at 1:1 ratio (stratified by gastrectomy, ECOG PS and prior chemotherapy) to receive paclitaxel oral solution (200mg/m 2 twice daily on days 1, 8, 15 of a 28-day cycle) or paclitaxel IV (175mg/m 2 on day 1 of a 21-day cycle). Co-primary endpoints were progression-free survival (PFS) assessed by blind independent review committee (BIRC) and overall survival (OS), with non-inferiority margin of hazard ratio (HR) of 1.18 for PFS and 1.16 for OS. Results: From April 22, 2019, to January 31, 2022 (data cut-off), 536 patients were randomized to receive either paclitaxel oral solution (n=268) or paclitaxel IV (n=268), with a median follow-up of 13.4 vs. 12.6 months. PFS met non-inferiority criteria, with BIRC-assessed median PFS of 3.02 months (95% confidence interval [CI]: 2.69, 3.71) in the oral group vs. 2.89 months (95% CI: 2.53, 3.48) in the IV group (HR=0.894, 95% CI: 0.719, 1.112, p =0.311). OS (cut-off on February 15, 2023, for OS primary analysis) demonstrated superiority for paclitaxel oral solution, with median OS of 9.13 months (95% CI: 7.72, 10.97) vs. 6.54 months (95% CI: 5.75, 7.26), showing 2.59-month improvement (HR=0.770, 95.5% CI: 0.635, 0.934, p =0.006). For the treatment-related adverse events (TRAEs), the oral group showed lower incidences of neuropathy (22.3% vs. 38.7% all grade), alopecia, fatigue, musculoskeletal and connective tissue disorders, and no hypersensitivity occurred without premedication. The most common ≥Grade 3 TRAEs were neutrophil count decreased (47.9% in oral vs. 54.5% in IV), white blood cell count decreased (41.5% vs. 35.3%) and anemia (16.6% vs. 10.9%). Grade 5 TRAEs were rare with comparable rates across two groups (four [1.5%] vs. three [1.1%]). Conclusions: Paclitaxel oral solution demonstrated non-inferiority in PFS and superiority in OS compared to paclitaxel IV, with clinically manageable and favorable safety profile, supporting paclitaxel oral solution as a second-line treatment option for gastric cancer. Clinical trial information: CTR20190050.

Understanding rates of attrition and barriers to surgical resection in patients undergoing neoadjuvant therapy for localized pancreatic cancer.

701 Background: Treatment paradigms are shifting toward neoadjuvant therapy (NAT) for resectable (R) and borderline resectable (BR) pancreatic cancer (PC) based on the rationale of treating occult metastatic disease, potentially downstaging patients (pts) to resectability if anatomically unresectable and, most importantly, selection of biology and pts most likely to benefit from potentially morbid surgery. While the benefits of NAT for PC have been well described, what remains underreported are the true attrition rates and underlying reasons for failure to proceed to surgical resection among pts receiving NAT. Herein, we present true intent-to-treat (ITT) attrition data of pts undergoing NAT for localized PC (LPC). Methods: Pts with LPC and who underwent ≥ 1 cycle NAT from January 2013-2022 were included. Clinicopathologic data were compared between those who did and did not proceed to pancreatectomy. Multivariable models identified factors associated with odds of attrition. Overall survival (OS) was estimated using the Kaplan-Meier method. Results: 427 LPC pts received NAT, including 57 (13%) with R, 133 (31%) BR, and 237 (56%) locally advanced (LA) disease. 64% had head tumors with median tumor size of 3.3 cm (IQR 2.7-4.2) and median CA 19-9 of 267 U/mL (IQR: 58-766). 60% of pts received FOLFIRINOX and 28% Gemcitabine-Abraxane for a median of 4.2 months (IQR 2.5-5.7). During NAT, 22% switched regimens and 30% received radiation. Following NAT, 207 (48%) pts underwent attempted resection, and 182 pts (43%) had successful pancreatectomy. The rate of attrition among all LPC pts was 52%, of which 20% had disease progression, 18% remained inoperable, 11% had physiologic decompensation, 2% were lost to follow-up, and 1% declined surgery. Rates of attrition were: 23% for R, 44% for BR, and 73% for LA (p&lt;0.01). Higher stage was associated with increased odds of attrition (OR 9.7, 95% CI 4.8 – 19.5 for LA and OR 3.0, 95% CI 1.4 – 6.1 for BR compared to R). The most common reasons for attrition were: metastatic progression (5% in R, 18% in BR, 26% in LA), the primary tumor was deemed inoperable (2% in R, 12% BR, 32% LA), or physiologic decompensation on NAT (7% R, 11% BR, or 12% LA). Pts undergoing pancreatectomy had a median OS of 30 vs 16 months for those not (p&lt;0.01). ITT median OS inversely correlated with stage – R: 30, BR: 21 and LA: 18 months (p&lt;0.01). There was no difference in OS for those who received NAT and resection – R: 31, BR: 27, and LA: 34 months (p=0.66). Conclusions: At a tertiary center with 87% BR and LA pts, 43% of pts proceeded to pancreatectomy following NAT including 27% with LA tumors. Attrition of pts remains a significant issue even in the setting of R, highlighting the importance of NAT in pt selection. Pts who receive NAT and pancreatectomy experience similar OS, regardless of stage, further supporting the NAT approach in choosing patients most likely to benefit from resection.

T cell dynamics with neoadjuvant immunotherapy in head and neck cancer

Controlling Ion Uptake in Carboxylated Mixed Conductors (Adv. Mater. 8/2025)

Ultrafast Lithium‐Ion Transport Engineered by Nanoconfinement Effect

Abstract Amid the burgeoning demand for electrochemical energy storage and neuromorphic computing, fast ion transport behavior has attracted widespread attention at both fundamental and practical levels. Here, based on the nanoconfined channel of graphene oxide laminar membranes (GOLMs), the lithium ionic conductivity typically exceeding 10 2 mS cm −1 is realized, one to three orders of magnitude higher than traditional liquid or solid lithium‐ion electrolyte. Specifically, the nanoconfined lithium hexafluorophosphate (LiPF 6 )‐ethylene carbonate (EC)/ dimethyl carbonate (DMC) electrolyte demonstrates the ionic conductivity of 170 mS cm −1 , outperforming the bulk counterpart by ≈16 fold. At the ultralow temperature of −60 °C, the nanoconfined electrolyte also maintains a practically useful conductivity of 11 mS cm −1 . Furthermore, the in situ experimental and theoretical framework enables to attribute the enhanced ionic conductivity to the layer‐by‐layer cations and anions distribution induced by high surface charge and nanoconfinement effects in GO nanochannels. More importantly, integrating such rapid lithium‐ion transport nanochannel into the LiFePO 4 (LFP) cathode significantly improves the high‐rate and long‐cycle performance of lithium batteries. These results exhibit the convention‐breaking ionic conductivity of nanoconfined electrolytes, inspiring the development of ultrafast ion diffusion pathways based on 2D nanoconfined channels for efficient energy storage applications.

Sex differences in the colorectal tumor immune microenvironment.

283 Background: Males have increased risk and mortality rates of colorectal cancer (CRC) compared to females, but the reasons for these disparities are not well understood. Immune responses differ by sex, and a robust T cell response is an important prognostic indicator in CRC. We hypothesized that females exhibit a stronger CRC-associated T cell response, contributing to reduced mortality in females compared to males. Methods: The study cohort included 2,751 incident CRC patients (1,337 female; 1,414 male) from a population-based case-control study. T cell receptor (TCR) abundance and clonality were quantified using immunoSEQ, and a gastrointestinal pathologist scored tumor-infiltrating lymphocyte counts per high-powered field (TILs/hpf). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between T cell metrics and sex, adjusting for age, anatomic site, and microsatellite instability (MSI) status. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals for the association between sex and 5-year all-cause and CRC-specific survival, adjusting for known prognostic indicators. We also conducted a formal test for interaction between sex and T cell features in relation to survival outcomes. Results: There were no associations between sex and TCR abundance (OR=1.05, 95% CI=0.98-1.13, p=0.14), TCR clonality (OR=0.99, 95% CI=0.91-1.06, p=0.72), or TILs/hpf (OR=1.05, 95% CI=0.88-1.25, p=0.60). We observed no differences in overall or disease-specific five-year survival between males and females. Further, the associations between T cell responses and survival did not significantly differ by sex. Conclusions: In a well-powered analysis, no robust sex differences were observed in the CRC immune microenvironment or in the relationship between T cell infiltration and CRC outcomes. The high burden of CRC and the emergence of immunotherapy as an important therapeutic approach suggest a need for further research investigating immunological sex differences in the setting of treatment response. Summary of associations between the colorectal tumor T cell response and sex. T cell Features Odds Ratio(Female vs. Male) Lower 95% CI Upper 95% CI P Value TCR Abundance 1.05 0.98 1.13 0.14 TCR Clonality 0.99 0.91 1.06 0.72 TILs/hpf* &lt;2 1.05 0.88 1.25 0.60 *A total of 99 patients (45 female; 54 male) with missing TILs/hpf data were excluded from the regression analysis.

Impact of next-generation sequencing in advanced gastrointestinal cancer.

814 Background: Next-generation sequencing (NGS) is a cutting-edge technology that allows for rapid DNA and RNA sequencing, identifying key mutations in cancer patients. It provides both diagnostic and predictive data for treatment decisions. Approximately 75.6% of US oncologists use NGS testing for patients with advanced solid tumors.This study retrospectively evaluates the impact of NGS testing on treatment outcomes for advanced GI cancer patients at a community-based cancer center in Florida. Methods: Between March 2019 and September 2023, 267 patients with stage 3 or 4 solid malignancies underwent NGS testing. Of these, 77 patients with advanced GI cancer were included in the study. Nearly half (48%) of the patients were diagnosed with advanced-stage colon cancer.NGS testing was performed using tissue samples (79.22%), blood samples (16.88%), or both (3.90%). Demographic and clinical outcomes, including time to diagnosis, treatment initiation, and survival, were collected and analyzed. Results: The median age of the study population was 70, with 88.31% of patients insured through Medicare. The cohort was composed of 61.04% males. Targetable mutations were identified in 59.74% of patients, leading to FDA-approved targeted therapies for 44.16%, and clinical trial eligibility for 79.22%. 52 patients were alive at the time of this analysis; those with biomarkers identified through NGS testing had a median treatment duration of 11 months regardless of whether testing impacted choice of therapy; whereas, patients without identified biomarkers had a median duration of 7.5 months. NGS testing impacted first-line therapy in only 6.49% of all patients; however, 80% of those patients were alive at the time of this analysis with a median duration of response of 5 months. Conclusions: NGS testing has become a cornerstone of oncologic care for advanced solid tumors; however, in this cohort of advanced GI malignancies, NGS results influenced first-line treatment decisions in only 6.49% of cases. Although the study included a small sample size, it reflects a real-world community setting where access to therapies and insurance coverage varies. For example, though patients may have targetable novel therapies available for their disease, the indications for such therapies may not be in the first line setting or covered by insurance. Advancements in NGS targeted therapies has greatly impacted the care of other solid malignancies such as non-small cell lung cancer; however, this study highlights that in the field of GI oncology, there is a large clinically unmet need of identifying newer biomarkers that are clinically relevant and impactful in earlier lines of oncologic care.

Influence of data review on community physicians’ treatment preferences in frontline esophageal cancer (EC).

501 Background: EC remains a global health challenge with a rising incidence and poor prognosis despite advancements in treatment modalities. Standard therapies include surgery, chemotherapy (CT), radiation therapy, and recently, targeted and immunotherapy. The PD-L1 inhibitors pembrolizumab (pembro) and nivolumab (nivo) received FDA approval for frontline treatment in EC in March and May 2021, respectively, based in part on the KEYNOTE-590 (KN590) and CheckMate 648 trials. In this study, we aimed to uncover rationale in physician preference for PD-L1 inhibitors in EC. Methods: US-based oncologists convened at two in-person meetings in April 2024 to discuss clinical and real-world data presented at the 2024 ASCO GI Cancers Symposium. Among data discussed included the KN590 5-year update. Survey questions were fielded at the meeting to capture participants’ impressions. Demographics were captured via an online survey ahead of the meeting. Responses from participants who manage EC and responded to all survey questions were aggregated. Results: 86 participants qualified; and, collectively, are 76% community physicians with 18 years average in clinical practice, see 18 patients median on clinic days, and spend 83% of their time in direct patient care on average. ECOG PS status (50%), tumor histology (52%), and location/stage (48%) were reported as critical factors in treatment decision-making; only 14% said PD-L1 status was a major factor. Participants were queried on a hypothetical patient case of esophageal squamous cell and adenocarcinoma before and after reviewing the KN590 data. Prior to reviewing KN590, physician preferences in the squamous cell 1L setting were split between nivo+CT and pembro+CT; following data review, pembro+CT was favored nearly 3:1. In the adenocarcinoma 1L setting, preference shifted from 60/40 nivo+CT to 60/40 pembro+CT, see Table. The cohort were most impressed with the overall survival (87%) and objective response rates (40%), and 55% would consider pembro+CT for both squamous cell and adenocarcinoma disease while 37% would consider it for PD-L1 CPS&gt;10 squamous cell disease only. Conclusions: Our study showed PD-L1 status was not a major factor in clinical decisions. The shift in treatment preference toward pembro+CT for both patient cases following KN590 data review suggests an impact for data review to influence physician behavior. This highlights the importance of educational initiatives to disseminate clinical updates to providers. It is still to be determined the optimal platform and length for these initiatives, and to quantify their effectiveness. 65-year-old male patient with advanced EC;PD-L1 CPS ≥10;ECOG PS of 1 Squamous cell disease Adenocarcinoma Before After Before After Fluoropyrimidine (FP) + platinum (P)-based CT 1% 1% 1% 0% FP +P-based CT + nivo 55% 27% 60% 36% FP + P-based CT + pembro 43% 71% 38% 63% Nivo + ipilimumab 1% 1% 0% 1% None of the above 0% 0% 0% 0%

Leptomeningeal metastatic disease: new frontiers and future directions