Browse Articles

A retrospective cohort studying integrative palliative care in a community oncology practice: Impact and outcomes.

12047 Background: Embedding palliative care within oncology practice supports symptom management and shared decision-making; however, its impact on real-world healthcare utilization and end-of-life planning is less well characterized. In 2018, a dedicated palliative oncology service was implemented at a Midwestern community cancer institute. We evaluated whether this integrated model was associated with differences in healthcare utilization, hospice referral, and advance care planning (ACP) compared with standard oncology care prior to implementation. Methods: We conducted an IRB-approved retrospective cohort study of adults with cancer treated at a single institution. Two age-, stage-, and histology-matched cohorts were identified: patients treated after implementation of the embedded palliative oncology service (2018–2021; Cohort A, n=300) and patients treated prior to implementation (2012–2017; Cohort B, n=300). Clinical data were extracted from the electronic medical record. Outcomes included emergency department (ED) visits, inpatient and ICU admissions, inpatient and ICU length of stay, hospice referral, and documented ACP. Continuous variables were compared using two-sample t-tests and categorical variables using χ² tests (α=0.05). Post-hoc power analyses were performed for outcomes demonstrating between-group differences. Results: Both cohorts were predominantly White (88% in Cohort A vs 93% in Cohort B) with a slight difference in mean age (70.8 vs 75.0 years). Cohort A included a higher proportion of patients with stage III–IV disease (74% vs 53%, p≤0.05). Compared with standard oncology care, the integrated palliative oncology model was associated with a higher mean number of ED visits (4.1 vs 3.0, p<0.05). There were no significant differences in inpatient admissions, ICU admissions, or inpatient length of stay between groups. Hospice referral and ACP documentation occurred significantly more frequently in Cohort A (both p<0.05). Post-hoc analyses demonstrated adequate power (>80%) to detect observed differences in ED utilization, hospice referral, and ACP documentation. Conclusions: Implementation of an integrated palliative oncology service was associated with increased ED utilization alongside substantially higher rates of hospice referral and ACP documentation, without an accompanying increase in hospital or ICU admissions or length of stay. These findings suggest that embedded palliative oncology may promote earlier end-of-life planning while maintaining stable inpatient utilization. Prospective studies are needed to better understand drivers of ED use and to further refine integrated palliative oncology care models.

Measuring KEYNOTE-522 response from TNBC patient biopsies ex vivo using the E-slice assay.

1132 Background: The KEYNOTE-522 regimen demonstrated a significant survival advantage of adding neoadjuvant pembrolizumab (pembro) to standard-of-care (SOC) chemotherapy (chemo) in TNBC patients. However, most patients will not benefit from this costly and potentially toxic therapy. A diagnostic test that can stratify responders and non-responders in advance will reduce overtreatment in this population. The E-slice assay is a proprietary 3D human tumor tissue culture platform that enables rapid, personalized drug sensitivity testing. E-slices preserve immune cells in their native state ex vivo, enabling immunotherapy response measurement from tissue resident immune cells. Methods: In this prospective clinical study, newly diagnosed triple-negative breast cancer (TNBC) patients scheduled to receive KEYNOTE-522 treatment at MD Anderson Cancer Center were enrolled. E-slices were generated from 14-gauge core biopsies and treated with IgG control, pembrolizumab, or a combination of pembrolizumab with paclitaxel + carboplatin followed by doxorubicin + cyclophosphamide. Diagnostic performance of the E-slice assay was evaluated using sensitivity, specificity, and ROC analysis, with the optimal cutoff determined by the Liu method. Concordance between assay-based predictions and clinical treatment response was assessed using Cohen’s kappa, and paired classification differences were tested with McNemar’s test. Patient tumor responders were defined solely by pathological complete response (pCR) or not, at the time of surgery, after standard-of-care neoadjuvant chemoimmunotherapy treatment. Results: A blinded interim analysis was scheduled after the first 10 patients evaluated in the clinic for pCR. The mean and SD of age were 52.10±12.52. The mean and SD for E-slice combo response, relative to DMSO @ day12 were 0.68±0.18. The optimal cutoff point for E-slice combo response was 0.78. The proportion of responders in patients was 0.8 (8/10). The proportion of responders from E-slice combo response was 0.7 (7/10). There was no significant difference based on McNemar’s test (p=1.0). The concordance rate is 75% (95% CI: 42.81%-94.51%). The sensitivity, specificity, positive predictive value, negative predictive value, and area under ROC curve at cutoff point for E-slice were: 87.5% (95% CI: 47.3%-99.7%), 100% (15.8%-100%), 100% (59%-100%), 66.7% (9.43%-99.2%), and 0.94 (0.82-1.0), respectively. Conclusions: E-slice assay predicts TNBC patient responses to pembrolizumab alone or pembrolizumab + chemo by providing drug sensitivity data in a clinically actionable time frame. Confusion matrices E-slice combo response. E slice Response Non-Responders Responders Total Patient Response Non-responders 2 0 2 Responders 1 7 8 Total 3 7 10 E-slice Responder was defined as E-slice combo response relative to DMSO @ day12 <0.7816. Non-responder was defined as ≥0.7816.

Preclinical study on the efficacy of CD4/TGF-β bispecific antibody (MR001) and temozolomide combination therapy for the treatment of multiple metastatic melanoma based on MagIC-PDX model.

e14504 Background: Advanced melanoma remains therapeutically challenging due to drug resistance, metastasis, and an immunosuppressive tumor microenvironment (TME). Temozolomide (TMZ) has demonstrated antitumor effects in melanoma in combination regimes. MR001 is a CD4/TGF-β bispecific antibody, first-in-class and first-in-human drug (approved by NMPA, 2023LP01942), which simultaneously activates CD4⁺ T cells and inhibits TGF-β signaling, reprogramming TME by limiting Treg-mediated immunosuppression, facilitating antitumor immune response, and increasing drug permeability. Conventional PDX is a powerful translational tool, but it has a low success rate, a lengthy establishment time, and requires high cost. Our previous studies proved that Magnetically-Induced Cell (MagIC) technology can expedite the reconstruction of the TME and the establishment of PDX (MagIC-PDX). This study aims to assess the efficacy of MR001 + TMZ in advanced metastatic melanoma in MagIC-PDX models. Methods: Metastatic melanoma MagIC-PDX models were established using NSG mice (n = 12) from fresh sample donated by a multiple metastatic melanoma patient in our hospital. In parallel, a murine model with humanized CD4⁺ (hCD4) mice (n = 32) were randomized into four groups: control, TMZ, MR001, and MR001 + TMZ; according to the patient all mice were engrafted with magnetized GFP/luciferase-labeled B16F10-GL cells into bone, subcutaneous tissue, and peritoneum using MagIC technology. Treatment was administered for 2 weeks along with bioluminescence imaging. TME remodeling was analyzed by immunofluorescence and qPCR. Concordance between the MagIC-PDX model and the corresponding patient clinical features was assessed. Results: In MagIC murine metastasis models, tumors developed at (3.9 ± 1.79) days. In the MR001 + TMZ group, both metastatic tumor size, qPCR, and bioluminescence signal are significantly decreased compared with both monotherapy groups (P < 0.001) and the control group (P < 0.001). Pathological examination showed that immunofluorescence signals of type III collagen encapsulation and decreased tumoral cell presence in the MR001 + TMZ group (P < 0.001), consistent with an immunoreactive and drug-permeable TME. The MagIC-PDX model behavior corresponds to the patient tumor, and the response to the combination treatment showed similar results compared to the murine model. Conclusions: MR001 synergizes with TMZ to exert potent antitumor activity in the murine multiple metastatic melanoma model and MagIC-PDX model. The MagIC-PDX model accurately reproduced patient-like metastatic dissemination. These findings support further development of MR001 based combination therapies and highlight MagIC-PDX as a rapid, patient-relevant platform for preclinical testing and precision modeling.

Real-world overall survival outcomes of BTK inhibitors vs. venetoclax-based therapy as second-line treatment for chronic lymphocytic leukemia.

7052 Background: Chronic lymphocytic leukemia (CLL) is a B-cell malignancy with highly variable clinical behavior. The treatment landscape has shifted from chemoimmunotherapy to targeted agents, specifically Bruton’s tyrosine kinase inhibitors (BTKi) and venetoclax (BCL-2 inhibitor). While both are established first-line options, the optimal treatment sequence to maximize long-term survival remains undefined. This real-world analysis evaluates overall survival (OS) when utilizing BTKi or venetoclax-based therapy as second-line (2L) treatment. Methods: This retrospective, propensity-matched cohort study utilized de-identified electronic medical record data from the TriNetX network (through Jan. 2026), covering 189 million patients. Adult patients with CLL (ICD-10: C91.1) were identified based on treatment sequencing of 1L BTKis followed by 2L Venetoclax or vice-versa. The index event was the initiation of 2L therapy with either a BTKi or venetoclax. Patients receiving traditional chemotherapy were excluded from analysis. To minimize confounding, 1:1 Propensity Score Matching (PSM) was performed using a greedy nearest-neighbor algorithm based on demographics (age, sex, race/ethnicity) and comorbidities (hypertension, ischemic heart disease, diabetes, CKD, COPD, obesity). Standardized mean differences (<0.1) confirmed covariate balance. The primary endpoint was OS through 10 years. Results: A total of 5,841 patients met inclusion criteria (BTKi n=2,589; venetoclax n=2,892). After PSM, 1,959 patients were included per cohort. Ten-year OS was significantly higher in patients receiving BTKi as 2L therapy compared to venetoclax (71.5% vs. 68.0%; HR 0.651, 95% CI 0.55-0.77; p <0.0001). Median follow-up duration was longer for the BTKi group (1,287 days) than the venetoclax group (639 days). Conclusions: In this real-world analysis, treatment sequence with Venetoclax (1L) and BTKis (2L) was associated with a significant long-term survival advantage compared to venetoclax. The observed reduction in mortality risk (HR 0.651) suggests that treatment sequencing of immunotherapy with Venetoclax followed by a BTKi may offer superior clinical outcomes for treatment of CLL. While these results support preferential sequencing of BTKis after venetoclax, additional prospective studies are needed for further evaluation and confirmation.

Real-world efficacy and safety of bispecific antibody ivonescimab-based regimens in EGFR-TKI–resistant advanced NSCLC.

8577 Background: Ivonescimab is a first-in-class bispecific monoclonal antibody targeting programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF)-A. In the phase III HARMONi-A trial, ivonescimab plus chemotherapy significantly improved progression-free survival (PFS) compared with chemotherapy alone in patients with epidermal growth factor receptor (EGFR)-mutant advanced non–small cell lung cancer (NSCLC) after resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, in real-world clinical practice, ivonescimab is administered across heterogeneous treatment lines after EGFR-TKI resistance, and evidence regarding its effectiveness in these settings remains limited. Methods: This real-world study included patients with advanced NSCLC who received ivonescimab plus chemotherapy following progression on EGFR-TKIs. The primary endpoints were median PFS (mPFS) and safety. Results: A total of 254 patients were included. At the data cutoff of November 30, 2025, the median follow-up was 8.9 months. The median age was 61 years; 54.3% were female, and 48.0% had brain metastases. The overall objective response rate (ORR) was 47.9%, with a mPFS of 6.9 months (95% CI, 6.2–7.5). A total of 124 patients were treated with ivonescimab plus chemotherapy immediately after EGFR-TKI resistance with HARMONi-A–like sequence and achieved an ORR of 52.9% with a mPFS of 7.0 months (95% CI, 4.5–9.4). The other 130 patients receiving ivonescimab plus chemotherapy after failure of prior immunotherapy-, anti-angiogenic therapy-, and/or chemotherapy-based regimens achieved an ORR of 43.1% with a mPFS of 6.7 months (95% CI, 6.0–7.4). No statistically significant difference in PFS was observed between the two groups ( p = 0.269). Grade 3–4 adverse events occurred in 14.6% of patients, including leukopenia (n = 9), neutropenia (n = 7), immune-related pneumonia (n = 6), and checkpoint inhibitor–related myocarditis (n = 5). Given the relatively short follow-up, overall survival data were not mature. Conclusions: In this real-world cohort, ivonescimab plus chemotherapy demonstrated clinically meaningful efficacy and a manageable safety profile when administered both immediately after EGFR-TKI resistance and following multiple prior lines of therapy, supporting its use across diverse treatment sequences in patients with EGFR-mutant advanced NSCLC.

First-line treatment of QLS31905 plus chemotherapy in patients with pancreatic cancer and gastric cancer: Data from a phase 1b/2 study.

4003 Background: QLS31905, a Claudin18.2/CD3 bispecific antibody, showed manageable safety and encouraging efficacy in Claudin18.2-positive patients (pts) with gastrointestinal tumors in a phase 1 trial. Here we report the safety and efficacy of QLS31905 plus chemotherapy in the first-line treatment of Claudin18.2-positive pts with pancreatic cancer (PC) and gastric cancer (GC). Methods: This phase 1b/2 trial recruited Claudin 18.2-positive (defined as ≥1% of tumor cells with ≥1+ staining intensity) pts with locally advanced unresectable or metastatic PC and GC who had not received systematic anti-tumor therapy. Pts with PC were administered QLS31905 at 350 μg/kg, 500 μg/kg, or 800 μg/kg Q2W or Q3W combined with gemcitabine plus nab-paclitaxel (Cohort 1). Pts with GC were administered QLS31905 at 500 μg/kg or 800 μg/kg Q3W combined with oxaliplatin plus capecitabine (Cohort 2). The primary endpoints were maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in phase 1b and was objective response rate (ORR) in phase 2. Results: As of Dec 11, 2025, 88 pts with PC and 43 pts with GC were enrolled. No dose-limiting toxicity occurred. MTD was not reached. RP2D was determined as 800 μg/kg Q3W for both pts with PC and GC. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 63 (71.6%) pts and 26 (60.5%) pts in Cohort 1 and Cohort 2, respectively. Ten pts (11.4%) in Cohort 1 and four pts (9.3%) in Cohort 2 discontinued any of the study treatment due to TRAEs. No QLS31905-related death occurred in both cohorts. In 82 efficacy-evaluable pts with PC, ORR and disease control rate (DCR) was 59.8% (95% confidence interval [CI], 48.34%-70.44%) and 89.0% (95% CI, 80.18%-94.86%), respectively. Median progression-free survival (PFS), duration of response (DoR), and overall survival (OS) was 8.74 months (95% CI, 7.16-10.71), 8.94 months (95% CI, 5.32-not evaluable [NE]), and 15.87 months (95% CI, 13.14-NE), respectively. In 15 pts with low Claudin18.2 expression in Cohort 1, ORR, DCR, median PFS, and median OS was 60.0% (95% CI, 32.29%-83.66%), 93.3% (95% CI, 68.05%-99.83%), 11.04 months (95% CI, 7.33-NE), and 15.61 months (95% CI, 3.98-NE), respectively. In 43 efficacy-evaluable pts with GC, ORR and DCR was 74.4% (95% CI, 58.83%-86.48%) and 93.0% (95% CI, 80.94%-98.54%), respectively. Median PFS and DoR was 10.09 months (95% CI, 6.87-NE) and not reached, respectively. In nine pts with low Claudin18.2 expression in Cohort 2, the ORR, DCR, median PFS, and 9-month PFS rate and was 77.8%, 100%, not reached, and 83.33%, respectively. Conclusions: QLS31905 plus chemotherapy in first-line treatment for Claudin18.2-positive pts with PC and GC showed manageable safety and potential efficacy. A phase 3 trial is ongoing to further confirm the efficacy and safety of QLS31905 in pts with PC. Clinical trial information: NCT06041035 .

Emerging trends in research strategies in the first-line recurrent or metastatic head and neck cancer (R/M SCCHN) landscape: A top-level analysis by Oncofocus.

e18029 Background: The current standard of care (pembrolizumab ± platinum-based chemotherapy and cetuximab + platinum-based chemotherapy) for the first-line (1L) treatment (Tx) of R/M SCCHN has set a median overall survival bar of ~13 months. Here, we present a top-level analysis of active regimens in this setting to identify emerging trends in research strategies aimed at improving the current benchmarks. Methods: Active regimens in the 1L R/M SCCHN space were identified from Oncofocus' internal knowledge base, which was developed through systematic screening of global clinical trial registries and validated using other authoritative sources. An analysis of the regimens was conducted to compile a list of unique therapeutic assets under evaluation. Emerging trends in targets and modalities were characterized based on key parameters, including trial phase and patient population. Results: With a data cut-off of Jan 19, 2026, 145 active regimens (111 unique assets) in the 1L R/M SCCHN pipeline landscape were included in this analysis. Across all ongoing studies, a total of 13 drug modalities are being evaluated, with the most common (≥5%) being monospecific antibody (37.8%, 42/111), small molecule (18.9%, 21/111), bispecific antibody (10.8%, 12/111), antibody-drug conjugate (10.8%, 12/111) and cancer vaccine (9.0%, 10/111). In terms of drug targets, 59 unique targets are being evaluated, with the most common being PD-1 (18.0%, 20/111), EGFR (12.6%, 14/111), and PD-L1 (7.2%, 8/111). Among the eight key Phase 3 trials (Table 1) that are evaluating novel combinations, all include PD-1 as one of the targets, aiming to build on the benefit seen with checkpoint blockade. Additionally, pembrolizumab is the preferred backbone agent (87.5%; 7/8) in these regimens. Conclusions: Current research trends indicate a shift in 1L Tx strategies for R/M SCCHN toward chemo-free combination therapies that target multiple pathways alongside PD-1 blockade. Additionally, future regulatory approvals may enable segmentation of the Tx algorithm based on key biomarkers, such as PD-L1 expression levels and HPV status. Key phase 3 trials in 1L R/M SCCHN. Trial acronym Regimen Targets Patient population Ph2/3 AHEAD-MERIT BNT113 + pembro HPV16 E6/7 + PD-1 HPV+, PD-L1 CPS ≥1 R/M SCCHN Ph3 ECLIPSE Cetuximab sarotalocan + pembro EGFR + PD-1 PD-L1 CPS ≥1, locoregional recurrent SCCHN Ph2/3 FORTIFI-HN01 Ficerafusp Alfa + pembro EGFR x TGF-β + PD-1 HPV–, PD-L1 CPS ≥1 R/M SCCHN Ph2/3 HexAgon-HN INBRX-106 + pembro OX40 + PD-1 PD-L1 CPS ≥20 R/M SCCHN Ph3 AK117-302 Ivonescimab + ligufalimab PD-1 x VEGF + CD47 PD-L1 CPS ≥1 R/M SCCHN Ph3 LiGeR-HN1 Petosemtamab + pembro EGFR x LGR5 + PD-1 PD-L1 CPS ≥1 R/M SCCHN Ph3 VERSATILE-003 Versamune HPV + pembro HPV16 E6/7 + PD-1 HPV+, PD-L1 CPS ≥1 R/M SCCHN Ph3 OrigAMI-5 Amivantamab + pembro + carboplatin EGFR x MET + PD-1 HPV–, R/M SCCHN

Postpartum-associated breast cancer: Patient outcomes analysis.

e12697 Background: Postpartum-associated breast cancer (PABC) has been defined clinically as breast cancer (BC) diagnosed within the first 5 years of the most recent birth. Though generally rare, incidence rates are increasing in conjunction with delayed childbearing and older maternal age at first birth. Currently, there are limited data regarding serial patient-reported outcomes in this patient population compared to non-PABC patients. Methods: Patients with PABC from the Mayo Clinic Breast Disease Registry who completed baseline, 2, and 4-year surveys were matched 1:1 to BC patients whose cancers occurred more than 5 years after their most recent birth (or in the setting of nulliparity) based on age, clinical stage, treatment received, and tumor subtype. Survey results from the Patient Health Questionnaire-2 (PHQ-2), Patient-Reported Outcomes Measurement Information System-10 (PROMIS-10), and Impact of Event Scale-Revised (IES-R) collected at approximately two and four years after diagnosis were compared between PABC and non-PABC patients. Univariable analyses used Wilcoxon rank sum tests, whereas multivariable analyses employed linear regression models adjusting for potential confounding effects. Results: A total of 222 individuals were included (111 with PABC). A higher proportion of individuals in the PABC cohort were married compared to the non-PABC cohort (80% vs. 42%, p < 0.001); otherwise, the groups were well-balanced across multiple categories, including age, gender, race/ethnicity, menopausal status, and germline mutation status. In univariable analyses, the Year 2 composite PHQ-2 score was significantly worse among individuals with non-PABC (p = 0.04), and the non-PABC cohort reported greater difficulty with sleep (p = 0.03) as measured by IES-R at Year 4. Both associations attenuated in a multivariable analysis controlling for marital status. In marital status-adjusted analyses of Year 4 survey results, PABC participants reported greater difficulty in carrying out social activities but were less likely to report emotional distress as evaluated by PROMIS-10 (compared with non-PABC participants). No other variables were significant univariably or multivariably (p > 0.05). Conclusions: In general, quality of life is similar among survivors of PABC compared to those diagnosed with breast cancer outside the postpartum period (or when nulliparous). However, our findings reveal that individuals with PABC are less likely to experience emotional distress 2 and 4 years after the BC diagnosis, which is unexpected, given that postpartum patients typically report higher levels of distress compared to their non-postpartum counterparts. Further investigation into these findings is warranted.

Predicting survival and treatment compliance of cancer patients enrolled in medication access programs across 20 countries.

e13514 Background: Cancer treatment access programs operate worldwide. This study applied classical and machine learning methods to access program administrative data to identify predictors of survival and treatment compliance of cancer patients. Methods: We performed a retrospective cohort study of patient records in a multi-country cancer medication access program database. The study examined the association between basic information collected during enrollment with the outcomes of survival and treatment compliance (defined as the proportion of prescribed medication cycles obtained on time). All patients enrolled between June 2016 and September 2025 were included. Survival was analyzed using Kaplan-Meier, Cox proportional hazards, and random survival forest. Compliance with treatment was analyzed using linear regression and an explainable boosted machine model. Analysis was performed in R and Python. The study protocol was developed prior to study execution. Data was obtained by querying the program database. Records with missing or inconsistent data were excluded. To account for confounding, all analyses included covariates capturing patient demographics and treatment context. Results: 18,556 patients met the inclusion criteria. 147 (0.8%) patients were excluded from the survival analysis due to missing (n = 116) or inconsistent (n = 31) data. 2,063 (11.1%) patients were excluded from the compliance analysis due to a missing compliance value (n = 1,928), missing data for other covariates (n = 116), or inconsistent data (n = 19). Final cohorts included patients from 16 low- and middle-income countries and 4 high-income countries. For the survival analysis, mean age at treatment start was 51.2 years (SD 18.1; sex ratio M:F = 0.85). Patients spent an average of 8.2 months (SD 8.6) in the access program, with 2,204 patients (12.0%) passing away while enrolled. All analyses revealed a strong association between survival and factors such as country, product, age, and program type while indicating a weak association for factors such as charity support and the specialty of a patient’s treating physician. For the compliance analysis, mean age at treatment start was 50.8 years (SD 18.1; sex ratio M:F = 0.82). Mean compliance was 78.9% (SD 35.7 pp). Both linear regression and an explainable boosted machine model showed country, product, and health insurance status as strongly associated with compliance, and other factors like sex, program type, and health facility type as having a weak association. Conclusions: This study identifies which data from access program administration is useful (and which is less useful) for predicting cancer patient survival and treatment compliance. Such predictions can help identify patients with higher mortality and non-compliance risk during enrollment and tailor interventions that improve these outcomes.

First-in-human dose-escalation study of the selective EGFR/HER2 exon 20 inhibitor PFL-721 in patients with locally advanced or metastatic NSCLC.

8619 Background: PFL-721 is a highly selective, orally bioavailable tyrosine kinase inhibitor (TKI) targeting activating EGFR & ERBB2 exon 20 (ex20) mutations while sparing wild-type (WT) EGFR. Preclinical studies demonstrate potent inhibition of diverse ex20 variants, >20-fold selectivity over WT EGFR, and robust antitumor activity in xenograft models. Methods: PFL-721 is investigated in an ongoing phase I study in patients (pts) with advanced NSCLC and EGFR/ERBB2 ex20 alterations (Clinical trial identifier: NCT06043817). PFL-721 is administered once daily (QD) in continuous 28-day cycles. Assessments included adverse events (AEs), dose-limiting toxicities (DLTs), PK, and antitumor activity by RECIST v1.1. Key eligibility criteria included locally documented EGFR/ERBB2 ex20 alterations on solid or liquid tumor biopsy, ECOG 0–1, and adequate organ function. Molecular responses were based on EGFR/ERBB2 ex20 alterations variant allele frequency decrease in ctDNA. Results: A total of 45 pts were dosed , with a median age of 63 years. Pts had received a median of 3 prior treatment lines. Thirty-one pts had EGFR ex20 alterations, 13 had ERBB2 ex20 insertion mutations, and one had both. Dose levels evaluated were 30, 60, 120, 240, 360, 480, and 600 mg QD. Dose escalation was completed with the identification of the maximum tolerated dose at 480 mg. AEs were reported in 43 pts (96%), including gastro-intestinal AEs in 39 pts (87%). Commonly observed grade ≥3 AEs included diarrhea (n=10/45, 22% of pts ), hypokalemia (n=4/45 , 9%), and increased blood creatinine (n=3/45, 7%). One grade 3 rash was observed. Six DLT events occurred in 39 evaluable pts, including grade 3 diarrhea (at 360 mg QD, n=2; 480 mg QD, n=1, 600 mg QD, n=1), grade 3 fatigue (600 mg QD, n=1), and grade 4 hypokalemia (600 mg QD, n=1). PK analyses showed dose-proportional exposure and achievement of plasma concentrations predicted to be effective based on preclinical models, at doses of ≥240 mg QD. Among efficacy population (n=42), partial responses (PRs) were observed in 15 / 28 pts at doses of ≥360 mg QD . The overall response and disease control rates at doses ≥360 mg QD were 54% (95%CI [33. 9-72.5]) and 79% (95%CI [59.0-97.7]), respectively. Among 25 evaluable pts, molecular responses (ctDNA decrease >50%) were observed in 12 at doses ≥120 mg. Conclusions: In this dose escalation study, class-effect local gastrointestinal AEs were observed in nearly all pts while the frequency of systemic skin toxicity was low, in line with the selectivity of the molecule for mutant EGFR. Antitumor activity was reported in 54% of pts at doses ≥360 mg QD in a heavily pretreated population, including with prior EGFR/ERBB2 ex20 TKI. Consistent with tumor shrinkage, ctDNA clearance was observed in 48% of evaluable pts. The randomized dose-optimization part is ongoing, with three dose regimens: 360 mg QD, 480 mg QD, and 240 mg BID. Clinical trial information: NCT06043817 .

Diffusion‐Selective Tandem Catalysis for Alkane Hydroisomerization

ABSTRACT The molecular diffusion behaviors in catalytic systems can influence product selectivity. Such a phenomenon, analogous to shape selectivity in zeolite catalysis, can be referred to as diffusion‐selectivity. However, diffusion‐selectivity is often neglected, and its connotation has scarcely been revealed. Herein, a tandem diffusion system of n‐alkene and i‐alkene intermediates in catalytic hydroisomerization was precisely modulated for the demonstration of intermediate diffusion‐selective effects. In a series of Pt/zeolite composites, the diffusion distance of n‐alkene intermediates from Pt sites towards zeolitic acid sites was prolonged by depositing Pt nanoparticles at the external surface of zeolite, leading to a reduced surface permeability by 20%, which facilitated the dispersion of n‐alkene intermediates and mitigated side‐reactions. On the contrary, the diffusion length of i‐alkene intermediates inside zeolites decreased with reduced channel length, resulting in an enhanced intracrystal diffusion by two orders of magnitude, which avoided the long‐time residence in zeolite and thus the secondary cracking of i‐alkene intermediates. In this case, a high isomer yield of 62% can be obtained, outperforming the counterparts and those reported in the literature. The proposed diffusion‐selective catalysis can be generalized to reactant and product diffusion‐selectivity.

Biofabrication of silver nanoparticles using Thevetia peruviana fruit extract for effective management of fungal pathogens and growth enhancement in solanaceous crops

IL-2-TGFβ co-agonist induces immune tolerance

Boosting Solid–Solid Conversion Kinetics via Electron‐Pinned Interface Engineering for High‐Energy‐Density Li‐S Batteries

ABSTRACT The pursuit of high‐energy‐density lithium–sulfur (Li–S) batteries necessitates the use of lean electrolyte conditions. However, this goal is severely hampered by the sluggish kinetics of the sulfur reduction reaction (SRR), especially in the “solid–solid” conversion stage, where each step requires distinct active sites with specific electron‐donating capabilities. Herein, we report a catalyst architecture that integrates “long‐range order” with “local disorder”, creating gradient‐ordered active sites through amorphous nanodomain modification and precise local electronic structure regulation. This catalyst, termed an electron‐pinned interface catalyst (EPIC) and denoted as a ‐FeOOH@Fe/AlO x , exhibits synergistic catalytic enhancement via multi‐level electronic interactions. Operando studies and DFT simulations reveal that the catalyst establishes conductive pathways facilitated by its gradient electron‐donating properties, thereby decoupling the SRR process and significantly enhancing the “solid–solid” conversion efficiency. Under lean electrolyte conditions, this catalyst achieves a high areal capacity of 10.7 mAh·cm −2 at a sulfur loading of 10.2 mg·cm −2 , exhibits 94.2% capacity retention after 150 cycles in a pouch cell, and enables stable operation of a 3.6 Ah pouch cell with an energy density of 418.6 Wh·kg −1 . This strategy effectively overcomes the reaction kinetic limitations in lean electrolyte conditions, providing valuable insights and a novel design paradigm for future high‐energy‐density Li–S batteries.

Deep learning for automatic segmentation of the inferior alveolar nerve using a hybrid CNN–transformer framework

National trends in melanoma-related hospitalizations, admission characteristics, and in-hospital outcomes in the United States, 2018–2022.

e21573 Background: Melanoma remains the most lethal form of skin cancer and contributes substantially to inpatient morbidity and healthcare utilization. Contemporary national data describing hospitalization patterns, admission characteristics, and outcomes for melanoma are limited, particularly in the modern treatment era. Methods: A serial cross-sectional analysis was conducted using the 2018–2022 Healthcare Cost and Utilization Project National Inpatient Sample. Adult (≥18 years) hospitalizations with a principal diagnosis of melanoma (ICD-10-CM C43) were included; all analyses were performed at the hospitalization level. National estimates incorporated discharge-level survey weights (DISCWT) with stratification (NIS_STRATUM) and clustering by hospital (HOSP_NIS). Outcomes included hospitalization volume, admission type (elective vs non-elective), in-hospital mortality, length of stay (LOS), and inflation-unadjusted hospitalization cost estimated using HCUP cost-to-charge ratios. Temporal patterns in mortality were summarized using annual survey-weighted proportions. Results: From 2018–2022, the NIS represented 32.4 million unweighted hospitalizations, corresponding to 162.2 million weighted hospitalizations nationally. Within this population, 1,817 unweighted hospitalizations had a principal diagnosis of melanoma, corresponding to an estimated 9,085 weighted melanoma hospitalizations nationwide and accounting for 26.8% of all principal skin cancer hospitalizations. Most melanoma hospitalizations were elective (56.6%; 95% CI 54.1–59.0), while 43.4% were non-elective. Overall in-hospital mortality was 5.3% (95% CI 4.2–6.6). Mean LOS was 4.8 days (95% CI 4.5–5.1), and mean hospitalization cost was $20,524 (95% CI $19,140–$21,907). Annual in-hospital mortality ranged from 3.9% to 6.4% without a monotonic change across the study period. Conclusions: Melanoma principal hospitalizations represent a substantial component of inpatient skin cancer care in the United States. More than half of admissions were elective, in-hospital mortality remained consistently near 5% over five years, and hospitalization costs were considerable despite relatively short LOS. These national benchmarks characterize the contemporary inpatient burden of melanoma and support ongoing evaluation of care delivery pathways to optimize resource utilization and shift appropriate management to outpatient settings.

Spatial architecture of tenascin-c–driven ECM–immune niches in sarcoma.

e23562 Background: Tenascin-C (TNC) is an extracellular matrix glycoprotein highly expressed during embryogenesis but largely silent in adult tissues and re-activated in cancer and inflammation. We hypothesized that TNC shapes an immunosuppressive sarcoma microenvironment by organizing ECM–macrophage spatial relationships. Methods: We profiled a commercial soft-tissue sarcoma TMA (64 cases/192 FFPE cores) including liposarcoma, angiosarcoma, leiomyosarcoma, MPNST, and synovial sarcoma. Multiplex OPAL IF assessed TNC, Fibronectin, NRP1, CD68, and CD163. HALO analytics included segmentation, heatmaps, nearest-neighbor (NN) distances, proximity metrics, and neighborhood analysis. Heatmaps localized ECM/immune hotspots; area quantification measured TNC-ECM burden; proximity tested per-cell macrophage distances to TNC; NN captured shortest intercellular coupling. We also established 18 custom TMAs from 180 samples (90 first diagnosis and 90 paired metastasis/progression). A 37-plex COMET panel was optimized for these TMAs, covering ECM macrophage phenotypes, EMT/plasticity, stemness, angiogenesis, TLS/immune architecture, and proliferation. COMET image analysis and survival correlations are ongoing. The targeting peptide PL1 (binding to TNC/fibronectin) was tested in JBT-19 cells. JBT-19 xenografts were examined by multiplex staining. Results: In the commercial TMA, multiplex imaging revealed distinct TNC-rich ECM architectures across sarcoma types. HALO heatmaps demonstrated that TNC-dense ECM micro-domains frequently co-localized with macrophage-rich clusters. Spatial metrics showed preferential accumulation of CD68⁺ macrophages along TNC-positive boundaries, whereas CD163⁺ and NRP1⁺ TAMs were enriched within the core of TNC-rich niches. NN and proximity analyses revealed significantly shorter macrophage–ECM distances (~10–20 µm) in these regions, suggesting directed positioning rather than random infiltration. Neighborhood mapping highlighted stable CD163⁺/NRP1⁺ TAM communities associated with TNC-structured ECM. JBT-19 xenografts recapitulated strong TNC and Fibronectin expression. PL1 peptide bound robustly to JBT-19 cells. COMET staining across 18 TMAs is fully established; quantitative spatial metrics and clinical-outcome mapping will be finalized before the congress. Conclusions: TNC-structured, TAM-enriched ECM niches constitute an immune-exclusion architecture that likely impedes T-cell trafficking and cytotoxicity in sarcoma. This stromal configuration may underpin resistance to immune-checkpoint therapies and contribute to suboptimal responses to cell therapies such as TCR-T. Xenograft staining corroborates the presence of TNC-rich matrix domains in vivo, and robust PL1 binding in JBT-19 cells underscores their tractability as therapeutic targets. Final COMET-based spatial metrics and outcome correlations will be presented at the meeting.

Geographical heterogeneity in modeled CA-125 KELIM values: Insights from more than 50,000 real-world calculations on the Biomarker Kinetics platform.

5550 Background: The modeled CA-125 KELIM is a pragmatic indicator of primary tumor chemosensitivity during neoadjuvant (NACT) or adjuvant chemotherapy (post-primary cytoreductive surgery: ADJUVANT) in ovarian cancer. In a recent GCIG meta-analysis, Japanese patients with stage III–IV high-grade serous carcinoma had higher median KELIM values than Western populations (Corbaux.et.al., Proc ESGO 2025). To further assess potential geographical variations in chemosensitivity, we analyzed KELIM values calculated via the free online platform www.biomarker-kinetics.org , which performs approximately 30,000 calculations annually worldwide. Methods: All CA-125 KELIM calculations performed on the BK platform between April 2024 and January 2026 were extracted. Median KELIM values were compared separately for NACT and adjuvant settings across continents and countries. Results: During the 21-month study period, 50,055 KELIM calculations were recorded worldwide (NACT 59%; ADJUVANT 41%), originating from Asia (n=27,280; 55%), Europe (n=16,461; 33%), North America (n=3,690; 7%), South America (n=1,363; 3%), and rest of globe. Marked geographical variations in KELIM distribution were observed. In the NACT setting, median KELIM values (standardized by the classical cutoff) were significantly higher in patients from Asia (median 1.06, 95%CI [1.05–1.07]), Middle-East (median 0.96 [0.89–1.0.6]), and North America (median 0.91 [0.89–0.94]) compared to those from Europe (median 0.85 [0.84–0.86]) (P <0.0001). Within Asia, KELIM values were similarly elevated in China (n=10,617; median 1.07 [1.06–1.08]) and Japan (n=3,092; median 1.05 [1.03–1.07]) (P=NS). Similar results were noted in the ADJUVANT setting (Asia median 0.91, North America 0.80, vs Europe 0.75; all P<0.0001). Weighted median (τ = 0.5) quantile regression confirmed significantly higher standardized KELIM values in Asia (+0.21), Middle East (+0.12), and North America (+0.06) compared with Europe in the NACT setting. Similar outcomes were found in ADJUVANT setting : Asia (+0.16), Middle East (+0.28), and North America (+0.04) compared to Europe. Conclusions: Consistent with the GCIG meta-analysis, this global extraction of >50,000 KELIM calculations in the last 2 years confirms substantial geographic variability in tumor chemosensitivity, with higher median standardized KELIM values observed in patients from Asia and, to a lesser extent, the Middle East, while those from Europe exhibited the lowest values. These findings suggest potential important worldwide differences in primary tumor sensitivity to 1st-line carboplatin-paclitaxel chemotherapy and support the need for further biological and clinical investigations across diverse geographic and ethnic populations.

Continued CNS-penetrant TKI therapy with or without local CNS therapy after brain metastasis diagnosis in NSCLC.

2036 Background: Patients with oncogene-driven metastatic non–small cell lung cancer (NSCLC) treated with CNS-penetrant tyrosine kinase inhibitors (TKIs) frequently develop brain metastases (BM) while continuing targeted therapy, and outcomes of adding local CNS-directed therapy in this setting are not well defined. We evaluated outcomes associated with local CNS therapy after post-TKI BM diagnosis. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults with NSCLC treated with osimertinib or lorlatinib who subsequently had a coded diagnosis of BM (ICD-10 C79.31) at least 1 month after TKI initiation and evidence of continued TKI use were included. Patients were stratified by receipt of CNS-directed local therapy (SRS/SBRT or neurosurgery) within 3 months of the index BM diagnosis versus no local therapy. The primary outcome was all-cause mortality within 180 days of the index event. Secondary outcomes included hospitalization and systemic corticosteroid use. Cohorts were balanced using 1:1 propensity score matching on demographics, comorbidities, extracranial disease, laboratory values, and TKI exposure. Survival analyses were performed, and proportional hazards assumptions were validated using Schoenfeld residuals (p>0.05). Results: Among 1,157 eligible patients, 1,053 matched pairs were generated. Within 180 days of the index brain metastasis diagnosis, mortality was lower among patients who received local CNS therapy compared with those who did not (10.9% vs 18.1%), corresponding to a hazard ratio (HR) for death of 0.54 (95% CI 0.43–0.68; p<0.001). Survival probabilities at 180 days were 88.7% in the local therapy cohort and 80.2% in the no local therapy cohort. Hospitalization within 180 days occurred in 20.3% of patients receiving local therapy and 22.4% of those without local therapy (p=0.24), with a nonsignificant trend toward delayed hospitalization (HR 0.84, 95% CI 0.69–1.01). Systemic corticosteroid use was common and similar between groups (61.3% vs 59.4%; p=0.40), with no significant difference in time to steroid initiation. In an osimertinib-only sensitivity analysis, 180-day mortality was 10.5% among patients receiving local CNS therapy compared with 19.4% among those without local therapy (HR 0.48, 95% CI 0.37–0.61; p<0.001). Conclusions: In this multi-institutional real-world cohort of patients with NSCLC receiving osimertinib or lorlatinib who developed BM, receipt of local CNS-directed therapy within 3 months was associated with lower 6-month mortality compared with continuation of targeted therapy alone, with consistent findings in an osimertinib-only sensitivity analysis. These results suggest a potential survival benefit of local CNS intervention in selected patients, while acknowledging residual confounding related to intracranial disease burden and clinical indication.

Pre-lymphodepletion CRP and ferritin risk stratification as a predictor of early immune toxicities and hematologic complications after CAR-T therapy: A propensity-matched cohort study.

7030 Background: Inflammation before CAR-T has been linked to higher rates of immune effector cell-associated toxicities and worse outcomes. A pragmatic pre-lymphodepletion risk stratification using C-reactive protein (CRP) and ferritin has been proposed to identify patients at elevated risk. We used the TriNetX Network to evaluate whether CRP/ferritin risk groups predict clinically relevant early outcomes following CAR-T in a real-world setting. Methods: We performed a retrospective study using TriNetX Network. Adults (≥18 years) treated with CAR-T (day 0) were included if CRP & ferritin were available in the pre-lymphodepletion window (day −20 to −5). Patients were classified as low risk (CRP <4 and ferritin <400), intermediate risk (CRP ≥4 with ferritin <400 or CRP <4 with ferritin ≥400), and high risk (CRP ≥4 and ferritin ≥400). Propensity score matching was performed using demographics, comorbidities, transplant status, malignancy diagnoses & lymphodepletion therapy. Outcomes were assessed from day 0 to +30. We analyzed outcomes using odds ratio (OR) with 95% confidence interval (CI) and time-to-event comparison using log-rank p-value. Results: After propensity matching, high vs low risk cohorts included 246 patients per group. For intermediate vs low risk, cohorts included 298 per group. High-risk patients had higher odds of cytokine release syndrome (CRS) (OR 1.56, 95% CI 1.1–2.2; p=0.04) and immune effector cell-associated neurotoxicity syndrome (ICANS) (OR 1.86, 95% CI 1.1–3.1; p=0.01) versus low risk. In intermediate vs low risk, ICANS remained increased (OR 1.69, 95% CI 1.1–2.7; p=0.02), while CRS showed a nonsignificant trend (OR 1.36, 95% CI 0.98–1.9; p=0.06). High risk cohort was associated with greater supportive care utilization, including higher odds of G-CSF use (OR 2.93, 95% CI 1.5–5.8; p<0.01) and blood transfusion (OR 2.65, 95% CI 1.2–5.9; p=0.01) versus low risk. High vs low-risk was associated with higher odds of platelets <50 (OR 3.59, 95% CI 1.98–6.5; p<0.01) and hemoglobin <8 (OR 2.81, 95% CI 1.3–5.9; p<0.01). Neutropenia (ANC <500) was not significantly different. In intermediate vs low risk, cytopenia-related endpoints were not significantly different. All-cause mortality analysis was not performed due to low event rates. Conclusions: In a TriNetX propensity-matched real-world cohort, a simple pre-lymphodepletion CRP and ferritin stratification identified CAR-T recipients at significantly higher risk for early immune toxicities (CRS, ICANS) and clinically meaningful hematotoxicities (severe thrombocytopenia and anemia) within 30 days, along with increased need for G-CSF & transfusion support. These findings support using simple pre-infusion inflammatory biomarkers to guide counseling, risk-adapted monitoring, and proactive supportive care strategies in routine practice.