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Circulating tumor DNA–based clinical-genetic (CG) prognostic model for radiographic progression-free survival (rPFS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Analysis of Alliance A031201.

5018 Background: mCRPC is characterized by marked molecular heterogeneity and variable clinical outcomes. Circulating tumor DNA (ctDNA) profiling provides a noninvasive approach to capture tumor genomic alterations with potential prognostic value. We developed and validated a ctDNA-based prognostic model for rPFS using data from the Alliance A031201 (NCT01949337) trial, distinct from our published CG model of overall survival (Halabi et al. Eur Urol 2025). Methods: We analyzed ctDNA from 776 pts enrolled in the A031201 trial that randomized men with chemotherapy-naïve mCRPC to enzalutamide +/- abiraterone acetate and prednisone. Baseline cell free DNA samples from 776 pts were sequenced using the AR-ctDETECT assay. The primary endpoint of this analysis was rPFS. Proportional hazards model was used to assess the association of each genetic alterations and clinical variables with rPFS. Random survival forest (RSF) incorporating CG and clinical (C) variables only were trained and evaluated using 10-fold cross-validation. Model performance was assessed using integrated time-dependent area under the ROC curve (itAUC) and net reclassification improvement (NRI). Results: Higher ctDNA aneuploidy fraction, ctDNA positivity, and multiple pathogenic genomic alterations were associated with worse rPFS. Among prevalent alterations, AR enhancer gain and AR gain were strongly prognostic, with median rPFS of 13.7 vs 27.3 months (mos) and 13.5 vs 27.0 mos for pts with and without alterations, respectively. The rPFS prognostic model included gains in AR, AR enhancer, MYC, CCND1, and FOXA1 , and losses in PTEN, TP53, and LRP1B based on RSF . PTEN loss, gains in AR enhancer, MYC, along with hemoglobin, PSA and alkaline phosphatase showed the largest contribution to risk prediction. Mean itAUC for C model was 0.66 (95% confidence interval [CI] 0.62-0.70), mean itAUC for CG model was 0.73 (95% CI: 0.69–0.77). At 22 mos (median rPFS), NRI comparing CG model with C model was 0.30 (95% CI: 0.19-0.36). Pts were stratified into low-, intermediate-, and poor-risk groups and showed markedly distinct rPFS outcomes, with median rPFS of 39.2, 25.2, and 12.8 mos, respectively. The hazard ratios for low vs poor risk was 0.25 (95% CI: 0.20–0.31) and for intermediate vs poor risk 0.46 (95% CI: 0.38-0.55). Conclusions: A ctDNA-based prognostic model integrating CG features robustly stratifies rPFS risk in pts with mCRPC treated with first line AR pathway inhibitor therapy. This approach may support individualized risk assessment and inform trial design around treatment intensification combinations and therapeutic decision-making. External validation in independent cohorts is warranted. Support: U10CA180821, U10CA180882; R01CA256157; R01CA174777; https://acknowledgments.alliancefound.org. Clinical trial information: NCT01949337 .

Impact of market entry of biosimilars in the US on cancer biologics' pricing strategies, market share, and payer costs.

11073 Background: Biosimilars have been anticipated to lower the financial burden of cancer for payors as well as patients. As of 2025, 42% (n=13 from three product lines: bevacizumab, rituximab, and trastuzumab) of physician-administered biosimilars launched in the US were indicated for cancer. These three product lines accounted for approximately $5.35 billion healthcare expenditure at clinics and nonfederal hospitals in 2024. Methods: Using MarketScan claims data and Average Sales Price (ASP) data from the Centers for Medicare & Medicaid Services, we calculated quarterly ASP of reference products to compare the pricing strategies of reference biologics for cancer vs. non-cancer treatment. We also compared the market share between cancer vs. non-cancer biologics and estimated the average monthly payor costs of the three cancer product lines 12 months before biosimilar entry versus 2023. We identified biologics using Healthcare Common Procedure Coding System codes and adjusted costs to 2025 USD using the prescription drugs Consumer Price Index. Results: Analyses included 8,252,400 claims of 8 reference products and 27 biosimilars. All three cancer biologics experienced biosimilar market entry starting late 2019. On average, the ASP of reference biologics for cancer decreased by 4.3% annually after biosimilar entry, contrasting to 17.2% decrease for non-cancer reference biologics. Meanwhile, the market share of reference biologics decreased on average 39.3%, 34.2%, and 35.4% annually for bevacizumab, rituximab, and trastuzumab, respectively, contrasting to 15.4% decrease for non-cancer reference biologics. Compared to monthly payor costs averaging over 12 months before the first biosimilar launch, monthly payor costs of biologics (including reference and biosimilars) in 2023 fell for all three cancer biologics in the commercial and Medicare market. The annual decrease rate in monthly payor costs was on average 45.1%, 52.0%, and 34.6% for bevacizumab, rituximab, and trastuzumab, respectively. Conclusions: After biosimilar entry, reference biologics for cancer reduced prices at a slower pace than non-cancer reference biologics, this pricing strategy led to a much faster decrease in their market share. Biosimilars for cancer, by gaining larger market share over time, has significantly reduced payor costs of cancer biologics for commercial and Medicare insurers. Drug Reference product ASP annual change Reference product market share annual change Commercial insurance mean monthly payor costs Medicare Part B mean monthly payor costs Before biosimilar entry 2023 Change Before biosimilar entry 2023 Change bevacizumab -2.1% -39.3% $5,261.9 $2,823.0 -46.4% $2,720.0 $1,526.8 -43.9% rituximab -4.4% -34.2% $7,187.4 $3,799.2 -47.1% $3,977.7 $1,717.1 -56.8% trastuzumab -6.5% -35.4% $4,781.6 $3,302.7 -30.9% $2,401.6 $1,485.0 -38.2%

Phase Ia study of VRN101099, a brain-penetrant, highly selective covalent HER2 inhibitor, in HER2-positive or HER2-mutant advanced solid tumors.

1048 Background: Despite advances in HER2-targeted therapies, including trastuzumab deruxtecan (T-DXd), unmet needs remain in patients with HER2-driven solid tumors who develop treatment resistance, particularly those with central nervous system (CNS) metastases. VRN101099 is an orally bioavailable, brain-penetrant covalent HER2 inhibitor that irreversibly inhibits HER2 and induces receptor internalization and degradation. Preclinical studies demonstrated antitumor activity in subcutaneous and intracranial xenograft models of HER2-positive breast and gastric cancers. Methods: This open-label phase Ia study assesses the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of VRN101099 in patients with HER2 IHC 1+/2+/3+ or HER2-activating mutant advanced solid tumors. A standard 3+3 dose-escalation design determines the maximum tolerated dose and recommended phase 2 dose (RP2D), with dose-limiting toxicities assessed during the first 21-day cycle. VRN101099 is given orally once daily in continuous 21-day cycles. Optional backfill cohorts may enroll up to 12 patients at tolerated dose levels to characterize safety, PK, and PD further. Data are descriptive as of the 18 January 2026 cutoff and inform ongoing dose escalation, backfill enrollment, and RP2D selection; early reporting reflects emerging safety and activity. Safety is overseen by a Safety Review Committee defined by protocol. Results: As of January 2026, 17 patients received VRN101099 (80–320 mg). Median age was 63 years; 65% were female, and 35% had breast cancer. HER2 IHC 3+ expression was seen in 29% of patients; 35% were ISH-positive, and 24% had HER2-activating mutations. Patients had received a median of 3 prior systemic therapies (range 0–10); 58% had prior anti-HER2 therapy, including T-DXd (47%). No Grade ≥3 treatment-related adverse events occurred. The most common treatment-related adverse event was Grade 1–2 diarrhea. Among eleven patients with at least one post-baseline tumor assessment at data cutoff, five with HER2 IHC 3+ expression or HER2-activating mutations experienced tumor size reduction after two cycles. Confirmed partial responses were observed in two patients previously treated with T-DXd: one with HER2 IHC 3+ breast cancer and one with HER2 S310Y-mutant NSCLC. PK analyses showed dose-dependent exposure, with trough concentrations at 240 mg exceeding preclinically defined HER2 inhibitory thresholds. Conclusions: VRN101099 was well tolerated across evaluated dose levels and demonstrated encouraging antitumor activity in heavily pretreated HER2-driven solid tumors, including patients previously treated with T-DXd. These findings support continued dose escalation and expansion to define the RP2D and further characterize the therapeutic potential of VRN101099. Clinical trial information: NCT06806982 .

The TIGeR-PaC phase 3 clinical trial examining intra-arterial gemcitabine versus intravenous gemcitabine: Pharmacokinetic and pharmacodynamic sub-study.

e16463 Background: Intra-arterial delivery of gemcitabine (IAG) targeted to tumors/tissue may provide higher local drug potency. 1 Furthermore, IAG may result in decreased systemic drug concentration and associated side effects due to intracellular delivery prior to conversion to gemcitabine’s inactive metabolite, difluorodeoxyuridine (dFdU). The ongoing TIGeR-PaC phase 3 trial is testing this approach in patients with locally advanced pancreatic cancer. Here we report the results of a 16-patient pharmacokinetics (PK) and pharmacodynamics sub-study within TIGeR-PaC. Methods: PK analyses were performed for a total of 16 participants across 6 TIGeR-PaC study sites; 11 participants received IAG with the RenovoCath dual balloon catheter at 1000 mg/m 2 over 20 minutes and 5 participants received intravenous gemcitabine (IVG) at 1000 mg/m 2 over 30 minutes. Blood was collected at T = -5, 10, 15, 20, 30, 40, 60, and 90 minutes from the onset of infusion for gemcitabine and dFdU assays. Maximum plasma drug concentration (C max ) and the area under the drug plasma concentration curve from time zero to the last measurable concentration (AUC 0-t ) were compared between the two groups. CA 19-9 tumor marker levels were measured prior to treatment and 2 weeks post-procedure. The relationship between AUC 0-t and the percent change in CA 19-9 levels was assessed; 3 patients with normal CA 19-9 baseline values were excluded from the analysis. Results: As previously shown, IAG results in lower gemcitabine C max and AUC 0-t compared to IVG. 2 Additional analyses showed the dFdU C max and AUC 0-t were higher for IAG compared to IVG, consistent with a more rapid conversion of gemcitabine to dFdU with targeted IAG compared to systemic IVG. With IAG administration, there was a direct correlation between increased dFdU levels and a reduction in CA 19-9 levels (Pearson’s r = 0.75; P = 0.034). These results suggest the conversion of gemcitabine to dFdU at the tissue level may provide a surrogate marker for drug response with IAG administration. Conclusions: In this analysis, localized IAG resulted in decreased systemic levels of gemcitabine compared to IVG, along with increased levels of its inactive metabolite dFdU. Thus, in addition to providing increased local potency, the IAG approach, in which gemcitabine is rapidly converted to its inactive metabolite, may be beneficial in decreasing gemcitabine-related systemic side effects. Clinical trial information: NCT03257033. Farsad K, et al. 2024. JVIR 35:1043-48 e3. Novelli P, et al. 2025. J Clin Oncol 43(4_suppl):719. Clinical trial information: NCT03257033 . Effects of treatment mode on mean pharmacokinetic parameters. PK parameter, mean (SE) IAG Group(N=11) IVG Group(N=5) P -value Gemcitabine: C max (mcg/mL) 12.9 (2.42) 14.6 (1.19) 0.535 AUC (hr ⋅ mcg/mL) 4.9 (0.94) 8.8 (0.99) 0.018 dFdU: C max (mcg/mL) 48.3 (5.61) 30.6 (2.20) 0.012 AUC (hr ⋅ mcg/mL) 46.3 (4.59) 37.1 (2.33) 0.097

Survival outcomes comparing sequencing of CAR-T followed by BiTE versus BiTE followed by CAR-T in patients with relapsed multiple myeloma.

7511 Background: Chimeric antigen receptor T-cell (CAR-T) therapies and bispecific T-cell engager (BiTE) antibodies for relapsed and refractory multiple myeloma (MM) are increasingly used earlier in the disease course but the optimal sequencing remains unclear. It has been hypothesized that CAR T before BiTE would lead to less T-cell exhaustion and better outcomes than BiTE before CAR T. Methods: A multicenter retrospective cohort study using the TriNetX Global Collaborative Network from 2021-2025 to evaluate outcomes among MM pts who received both CAR-T (idecel or ciltacel) and a BiTE (teclistamab, talquetamab, or elranatamab). Cohorts by treatment sequence: CAR-T followed by BiTE (CAR-T→BiTE) or BiTE followed by CAR-T (BiTE→CAR-T). Primary outcome: 5-yr mortality from the initiation of first advanced immunotherapy. Secondary outcomes: incidence of CRS, ICANS, infection, sepsis, ICU admission, and 1-yr mortality following each therapy. Propensity score matching included demographic variables, comorbidities, prior myeloma therapies (including prior SCTx) and baseline laboratory values. Results: 389 pts were included (244 CAR-T→BiTE; 145 BiTE→CAR-T); in the CAR T 1st group, 72% received ide-cel and 28% had cilta-cel, whereas in the BiTE 1st group 86% went on to receive cilta-cel as the CAR T product. Median overall survival was reached in the BiTE-first cohort (3.59 years) but not in the CAR-T–first cohort. Five-year survival was significantly higher with CAR-T–first sequencing (57.1% vs 25.5%; log-rank p = 0.045). In adjusted Cox regression, CAR-T–first sequencing was independently associated with lower 5-year mortality (hazard ratio 0.57, 95% CI 0.34–0.95). In unmatched analyses stratified by the specific BiTE (anti-BCMA vs anti-GPRC5D) used, overall survival did not differ significantly within each treatment sequence (all log-rank p > 0.05). In propensity score–matched analyses (112 patients per group), CAR-T–first pts experienced higher ICANS (all grades, 22% vs 10.7%) after first therapy but lower ICU admission (52% vs 70%), and significantly lower CRS (37% vs 56%, all grades) following second therapy. Rates of infection, sepsis, and 1-yr mortality were similar between groups. Conclusions: Among patients with MM who received both CAR-T and BiTE therapies, CAR-T–first sequencing was associated with significantly improved long-term survival in spite of a much higher percentage receiving the less effective CAR T product. The additional finding of a lack of survival differences by specific BiTE used also suggests that treatment order, rather than product selection, may be the primary determinant of long-term outcomes. These findings support consideration of earlier CAR-T deployment when feasible and underscore the importance of sequencing strategy in the evolving landscape of MM immunotherapy.

First-line immunotherapy strategies in pMMR advanced endometrial cancer: A network meta-analysis.

e17650 Background: Optimal first-line treatment for mismatch repair–proficient (pMMR) advanced or recurrent endometrial cancer remains uncertain in the setting of multiple emerging immunotherapy-based regimens. We conducted a network meta-analysis to compare chemotherapy-based versus chemotherapy-free immunotherapy strategies. Methods: We performed a frequentist network meta-analysis of randomized controlled trials evaluating first-line systemic therapy in primary advanced or recurrent pMMR endometrial cancer using the R-based NetMetaEasy tool. Progression-free survival (PFS) hazard ratios (HRs) were synthesized using a random-effects model, with carboplatin–paclitaxel (TC) as the common comparator. Strategies included TC plus pembrolizumab, dostarlimab, durvalumab, atezolizumab, durvalumab plus olaparib, dostarlimab plus niraparib, and lenvatinib plus pembrolizumab. Results: Seven randomized trials comprising eight treatment strategies were included. Chemotherapy-based immunotherapy combinations improved PFS compared with TC alone, whereas the chemotherapy-free regimen lenvatinib plus pembrolizumab did not. Significant PFS benefit versus TC was observed for TC plus pembrolizumab (HR 0.54, 95% CI 0.41–0.71), TC plus durvalumab with olaparib (HR 0.57, 95% CI 0.44–0.73), TC plus dostarlimab with niraparib (HR 0.63, 95% CI 0.44–0.91), TC plus dostarlimab (HR 0.76, 95% CI 0.59–0.98), and TC plus durvalumab (HR 0.77, 95% CI 0.61–0.98). No significant benefit was observed with TC plus atezolizumab (HR 0.92, 95% CI 0.73–1.16) or lenvatinib plus pembrolizumab (HR 0.99, 95% CI 0.81–1.20). Network estimates favored TC plus pembrolizumab over lenvatinib plus pembrolizumab (HR 0.55, 95% CI 0.39–0.76). P-score ranking identified TC plus pembrolizumab (0.90) and TC plus durvalumab with olaparib (0.85) as top regimens. Conclusions: In pMMR advanced endometrial cancer, first-line immunotherapy strategies incorporating chemotherapy provide the greatest PFS benefit within available randomized evidence. Chemotherapy-free immunotherapy did not improve outcomes versus standard chemotherapy, supporting chemotherapy-based immunotherapy as the preferred first-line approach.

Artificial intelligence–enabled analysis of prognostic PI3K pathway alterations in African American colorectal cancer patients treated with FOLFOX.

e15511 Background: The phosphoinositide 3-kinase (PI3K) signaling pathway regulates tumor growth, metabolism, and treatment response in colorectal cancer (CRC). African American (AA) patients experience a disproportionate CRC burden yet remain underrepresented in molecular studies assessing chemotherapy-associated biomarkers. The prognostic significance of PI3K pathway alterations across ancestry, age at diagnosis, and FOLFOX exposure remains poorly defined. Methods: We performed a retrospective analysis of 2,562 CRC patients with genomic, clinical, and treatment data from public datasets. Cohorts were stratified by ancestry (AA vs. non-Hispanic White [NHW]), age at diagnosis ( < 50 vs. ≥50 years), and FOLFOX treatment. PI3K pathway alterations (including MTOR, AKT3, and PPP2R1A) were analyzed using Fisher’s exact test. Overall survival (OS) was assessed by Kaplan–Meier and Cox models. AI-HOPE conversational AI agents enabled reproducible cohort stratification and integrated analyses. Results: FOLFOX-exposed AA late-onset CRC (LOCRC) tumors showed fewer mTOR mutations than unexposed tumors (0% vs. 9.9%, p = 0.04). In NHW early-onset CRC (EOCRC), FOLFOX exposure was associated with lower AKT3 mutation frequency (0.8% vs. 3.0%, p = 0.04). NHW LOCRC tumors treated with FOLFOX had reduced PPP2R1A (1.7% vs. 3.5%, p = 0.03) and mTOR mutations (4.5% vs. 7.8%, p = 0.007). PI3K pathway alterations were associated with improved OS in AA LOCRC not treated with FOLFOX (p = 0.039), NHW EOCRC treated with FOLFOX (p = 0.0008), and NHW LOCRC not treated with FOLFOX (p = 0.005). However, PI3K pathway alterations did not have prognostic significance among FOLFOX-treated or -untreated AA EOCRC patients and among FOLFOX-treated AA LOCRC patients. Conclusions: PI3K pathway alterations demonstrate ancestry-, age-, and treatment-specific prognostic associations in CRC. AI-enabled, ancestry-aware analyses highlight the PI3K pathway as a context-dependent biomarker and support the integration of artificial intelligence to advance equitable precision oncology.

Pre-diagnostic imaging and radiology report–based risk modeling for pancreatic ductal adenocarcinoma.

e16017 Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and remains one of the deadliest malignancies worldwide, largely due to late-stage diagnosis. Early-stage PDAC is frequently asymptomatic, limiting opportunities for timely detection and intervention. We aimed to develop prognostic models using routinely acquired pre-diagnostic clinical data to identify individuals at high risk for PDAC prior to clinical manifestation. Methods: We conducted a retrospective study of patients treated at Mayo Clinic sites in Rochester, MN; Phoenix, AZ; and Jacksonville, FL between January 2011 and February 2023. The cohort included 1,151 patients with PDAC and 3,745 noncancer controls. CT scans were standardized to axial abdominal acquisitions with slice thickness between 0.8–3.0 mm. Radiology reports were de-identified, normalized, and parsed into structured sections (Indications, Findings, Impression), with an additional pancreas-specific section aggregating pancreas-related sentences. Demographic and clinical variables, e.g., age, sex, race, etc., were encoded using a templated sentence representation. All textual inputs were embedded using a Sentence-BERT model. A multimodal deep learning survival model was developed to integrate CT imaging, radiology report embeddings, and demographic features. The model was trained using a negative log-likelihood loss to estimate patient-specific PDAC risk scores. Model performance was assessed using the concordance index (C-index). Internal validation included patients from MN and AZ sites, while external validation used the FL cohort. Results: We evaluated unimodal (imaging, text, and demographics) and multimodal inputs. Fusion of imaging, radiology report, and demographic features achieved the highest performance, with internal and external validation C-indices of 0.885 (95% CI, 0.856–0.908) and 0.751 (95% CI, 0.719–0.783), respectively. Subgroup analysis by tumor location demonstrated differential performance. For pancreatic head tumors, internal and external C-indices were 0.916 (95% CI, 0.841–0.960) and 0.778 (95% CI, 0.730–0.823). For pancreatic body tumors, C-indices were 0.954 (95% CI, 0.897–0.997) internally and 0.929 (95% CI, 0.897–0.953) externally. For pancreatic tail tumors, internal and external C-indices were 0.903 (95% CI, 0.830–0.974) and 0.789 (95% CI, 0.689–0.874). Conclusions: A multimodal deep survival model leveraging pre-diagnostic CT imaging, radiology report embeddings, and demographic data can effectively identify individuals at high risk for PDAC prior to clinical diagnosis. Differences in performance were observed across pancreatic head, body, and tail tumors. This approach highlights the potential of opportunistic cancer risk stratification from routine imaging to enable earlier detection and targeted intervention strategies.

Rethinking cancer attribution in oncology VBC models: E&M vs treatment-based approach.

1580 Background: Patients with multiple cancers are uncommon. In value-based care models such as EOM (Enhancing Oncology Model),episode attribution and financial accountability rely on assigning a cancer type based on the plurality of predefined E&M visits. However, this administrative approach may not accurately represent the cancer for which a patient is receiving active treatment, especially in the presence of concurrent malignancies. Despite this, little is known about how often the E&M based cancer type differs from the treatment-based cancer type. Methods: We analyzed EOM performance period data (July 2023–June 2025) from practices in The US Oncology Network. Injected based initiating episodes were identified using EOM Part B claims that occurred at practices’ sites, then matched to the Electronic Health Record by patient, drug, and initiating date. For oral agents, additional to patient, drug and prescribing provider, order dates within 60 days of the fill date in Part D Claims was used as a proxy in matching process. Cancer type associated with the initiating treatment was extracted from the EHR and then compared with EOM-attributed cancer types. Results: Episodes were predominantly triggered by injection-based chemotherapy with 13,803 initiated in physician office setting, and 5,441 were initiated by oral chemotherapy. Matching rates to an initiating event in EHR differed substantially by route:~ 90% for injection-initiated episodes vs. about 40% for oral-initiated episodes. Among injection-based episodes, 5% of episodes did not have a treatment-based cancer diagnosis in EHR and 4.5% had discordant cancer diagnoses, while oral-based episodes showed markedly higher rates of missing cancer diagnosis at 32%, with 24% mismatched diagnoses. Chronic leukemia and prostate had a higher proportion of oral initiations and correspondingly lower matching rates. Oral-initiated episodes demonstrated particularly low EHR matching in breast, lung, prostate, and small intestine/colorectal cancers. Conclusions: Cancer attribution in VBC models remains challenging, particularly for episodes initiated with oral therapies. As the use of oral agents continues to expand and patients increasingly present with concurrent cancers, attribution difficulties are likely to grow, resulting in greater discordance over time. Incorporating treatment-based cancer type into attribution could improve accuracy and better align assigned cancer types with actual care in value-based oncology models. EHR matching by route of chemotherapy initiation. Cancer Type Injection Episodes (n) Injection Concordance (%) Oral Episodes (n) Oral Concordance (%) Breast Cancer 3836 91.8% 727 23.9% Chronic Leukemia 171 83.6% 1370 50.1% Lung Cancer 3539 93.1% 323 31.3% Lymphoma 1724 84.6% 512 47.9% Multiple Myeloma 1976 93.2% 1211 73.6% Prostate Cancer 558 83.2% 1210 21.4% Small Intestine/Colorectal Cancer 1999 89.1% 88 21.6%

Quasi‐Crowding Solvation Design of Ionic Liquid Electrolytes for Stable High‐Temperature Potassium‐Ion Batteries

ABSTRACT A quasi‐crowding solvation structure design principle was proposed to develop phosphate‐mediated ionic liquid electrolyte (PILE), enabling high ionic conductivity, low desolvation energy barrier, enhanced anion‐dominant nature of the inner solvation sheath, and re‐stabilization of organic cations in the outer solvation sheath. As a result, the Prussian Blue (PB) cathode in PILE delivered a highly maintained specific capacity of 62.0 mAh/g after 800 cycles at 500 mA/g and 20°C, which can be further improved to be 80.7 mAh/g after 500 cycles at 40°C. The synergistic effect from the quasi‐crowding solvation design guaranteed stability, and elevating working temperatures enhanced kinetics, which was revealed to be responsible for the improved K‐storage performance, mainly via transforming the cathode‐electrolyte‐interphase (CEI) formation mechanism from organic‐cation‐dominated to fluorine‐rich‐anion‐dominated oxidation, and significantly reducing ion transport and charge transfer impedances, respectively. The developed PB||PILE||graphite (Gr) full cell also output a significantly improved energy density of 269.6 Wh/kg and power density of 609.9 W/kg at 200 mA/g and 60°C, attributing to the efficient activation of low‐spin Fe‐C sites for deep and high‐voltage K‐storage. These principles and validations will significantly advance the understanding of fundamental electrolyte chemistry and inspire the rational design of high‐performance potassium‐ion batteries (PIBs) for extreme applications.

Surface morphology and performance evaluation of ZnO/PANI nanoparticle-based gas sensor: An overview

Cationic Potential‐Driven Surface Reconstruction Enables Stable High‐Voltage Cylindrical Sodium‐Ion Batteries

ABSTRACT Reconciling the trade‐off between high specific capacity and high‐voltage structural stability is the “holy grail” for advanced sodium‐ion batteries. While constructing O3/P2 multiphase heterostructures offers a theoretical solution, preventing stochastic phase distribution while maintaining atomic‐level precision during scalable synthesis remains a formidable hurdle. Herein, a scalable cationic‐potential‐driven surface reconstruction strategy is developed to engineer the interface of O3‐type layered cathodes (O3‐Na 0.9 Mg 0.1 Ni 0.35 Mn 0.35 Ti 0.20 O 2 ). Leveraging a significant ionic potential gradient, the incorporation of a high‐ionic‐potential modifier induces a self‐limiting, nanometric, and Na‐deficient P2 shell that homogeneously encapsulates the O3 core via a coherent epitaxial interface. This robust architecture effectively suppresses lattice oxygen release and transition metal migration while preserving expanded interlayer spacing for rapid Na + kinetics. Consequently, the resulting O3‐core@P2‐shell material delivers excellent cycling stability, retaining 76.3% of its capacity after 400 cycles at 2 C (2.0–4.4 V), vastly outperforming the pristine counterpart (47.8%). Notably, the industrial feasibility (550 g/batch) of this strategy is validated in 1.5 Ah 18650 high‐voltage cylindrical batteries, which maintain 82% capacity after 400 cycles. This work establishes an effective paradigm for harmonizing atomic‐level precision with mass production, unlocking a tangible pathway for high‐energy‐density and long‐life sodium‐ion storage.

Short‐Wavelength Infrared Imaging with Organic Photodetectors Based on Non‐Fullerene Acceptors with Detection above 1200 nm

ABSTRACT Organic photodetectors (OPDs) have emerged as promising candidates for next‐generation light‐detecting technologies. Compared to traditional inorganic photodetectors (e.g. silicon and indium gallium arsenide), OPDs offer advantages including lower fabrication cost, intrinsic mechanical flexibility, and tunable detection range. However, their performance still lags behind that of traditional detectors, particularly in the near‐infrared region. In this work, two low band gap non‐fullerene acceptors, BZIC‐2F and BZIC‐2Cl are synthesized, both exhibiting absorption onsets beyond 1200 nm. OPDs based on BZIC‐2F deliver superior performance when blended with the low‐cost donor P3HT, achieving spectral responsivity values of 0.49 A W −1 (1010 nm under −2 V) and a specific detectivity of 1.30 × 10 12 Jones, outperforming benchmark commercial silicon detectors in the shortwave infrared (SWIR) range, while maintaining stable photoresponse over 3 million on/off illumination cycles. Furthermore, a prototype blade‐coated active‐matrix imager is fabricated in air on an amorphous silicon backplane. The imager exhibits a broadband light detection range spanning from visible to SWIR, enabling practical applications such as faint infrared light imaging, semiconductor wafer inspection, LiDAR light detection, and banknote verification. Combined with detailed materials cost analysis, this work represents the first demonstration of an integrated active‐matrix imager employing a fully organic semiconductor photoactive layer capable of high‐speed SWIR imaging, highlighting its promise for a scalable and cost‐effective next‐generation SWIR photodetector.

Chemical composition and insecticidal activity of Salvia rosmarinus ‘Eretto Liguria’ essential oil against tomato leaf miner (Tuta absoluta)

Use of visual analogue scale (VAS) and analgesia administration in oncology inpatients: An audit from a tertiary care centre.

e24061 Background: Effective pain assessment and timely administration of analgesia are essential components of quality care, particularly in oncology. The Visual Analogue Scale (VAS) is a widely validated, simple tool for quantifying pain intensity and guiding appropriate analgesic selection. However, documentation gaps and delays in analgesic administration may compromise patient comfort and overall treatment experience. This audit was undertaken to evaluate adherence to standardized pain assessment and management practices in the oncology ward of a tertiary care hospital. The aims were to (1) assess the proportion of patients with VAS documented at admission, (2) determine the proportion of patients with VAS ≥ 1 who received timely and appropriate analgesia, and (3) compare findings across three PDSA audit cycles to assess quality improvement. The benchmarks used was 100% of patients should have a VAS documented at admission. Methods: The analysis was conducted from October 4, 2025 to January 10, 2026 as a quality improvement audit of pain management practices in the oncology ward using the WHO analgesic ladder and Visual Analogue Scale (VAS) for pain assessment, structured in a PDSA (Plan–Do–Study–Act) framework. Three PDSA cycles evaluated the impact of repeated education and protocol reinforcement on VAS compliance and WHO ladder adherence. Pain severity and management were categorized according to WHO recommendations: Step 1—non-opioid ± adjuvants for mild pain (VAS 1–3); Step 2—weak opioid ± non-opioid for moderate pain (VAS 4–6); Step 3—strong opioid ± non-opioid for severe pain (VAS 7–10). Results: Across the three PDSA audit cycles (total n = 120), a progressive improvement in pain assessment and management practices was observed (table 1). In the first cycle it was realized that nursing team could not do real time capture of VAS in hospital information system due to logistic challenges. The capture was thereafter changed to a manual system. Conclusions: The audit highlights the critical importance of structured pain assessment and education in improving pain management practices in oncology patients. Progressive improvement in VAS documentation and adherence to the WHO analgesic ladder across consecutive audit cycles demonstrates that regular reinforcement and staff training significantly enhance compliance with pain management protocols. Audits, multidisciplinary engagement, and continued education are essential to achieve consistent, patient-centered pain relief in accordance with WHO standards. Parameter Cycle 1 (n=40) Cycle 2 (n=40) Cycle 3 (n=40) VAS documented, n (%) 26 (65%) 26 (65%) 40 (100%) VAS not documented, n (%) 14 (35%) 13 (32.5%) 0 (0%) Patients with VAS ≥ 1, n (%) 0 (0%) (Documentation error in HIS) 3 (7.5%) 13 (32.5%) Analgesia administered, n (%) 0 (0%) (Documentation error in HIS) 1 (2.5%) 5 (12.5%) WHO ladder adherence Limited Limited Improved

Activity of NP-G2-044 (fascin inhibitor) + anti–PD-1 in ICI-resistant advanced/metastatic solid tumors with expansion in cutaneous squamous cell carcinoma (CSCC).

e21557 Background: Most patients do not respond to anti–PD-1 therapy, and many responders develop acquired resistance. In CSCC, response rates are ~50%, and acquired resistance occurs in ~35% of initial responders, highlighting the need to convert ICI-refractory or acquired-resistant tumors into responders. NP-G2-044 is a first-in-class fascin inhibitor that activates intratumoral dendritic cells (DCs), enhancing antigen uptake/activation, increasing tertiary lymphoid structures, and promoting IL-12/IFN-γ–dependent antitumor immunity that can synergize with PD-1 blockade; fascin inhibition also suppresses new metastasis formation. Methods: NP-G2-044-P2-01 is a Phase 2 study evaluating NP-G2-044 orally QD in combination with anti-PD-1 therapy across multiple tumor-specific expansion cohorts, in patients with ICI-refractory disease or acquired resistance without molecular biomarker selection. The primary endpoint is confirmed ORR per RECIST 1.1 with secondary endpoints including DCR, DOR, and PFS. Safety was assessed by CTCAE. Results: 45 patients with primary ICI-refractory disease or acquired ICI resistance were evaluable for efficacy. CR and PR were observed across 7 tumor types, including 5 composite CRs (RECIST, clinical, or pathological) in cervical, endometrial, CSCC, pancreatic, and gastroesophageal junction adenocarcinomas. 3 patients are off treatment and disease-free for > 1 year, and 3 patients are with PFS > 2 years. Median MFI was 14 months. In the CSCC cohort (efficacy population N = 6), responses included 1 RECIST CR, 1 clinical CR (residual deep scarring only), and 1 pathological CR, for ORR 50% (3/6) and confirmed DCR 100% (6/6). In the clinical CR case, tumor-informed ctDNA was detectable at baseline, cleared after 8 weeks of treatment, and has remained negative for > 2 years; the patient remains in clinical CR one year after stopping therapy. TEAEs (n = 56) were predominantly grade 1/2; common TEAEs (≥20%) were fatigue, nausea, ALT increased, AST increased, and vomiting. Study drug–related AEs were mostly grade 1/2 (66%), with grade 3 in 8.9% and grade 4 in 1.8%, with no new safety signals. Mechanistic analyses using multiplex immunofluorescence and immunophenotyping showed increased intratumoral CD8⁺ T-cell infiltration and proliferation, along with increased intratumoral activated DCs, consistent with a strong immunomodulatory response. Conclusions: NP-G2-044 plus anti–PD-1 demonstrated pan-tumor activity in ICI-resistant advanced/metastatic solid tumors with durable benefit, including responses persisting after treatment cessation. In advanced/metastatic ICI-resistant CSCC, the regimen achieved 50% ORR and 100% disease control with durable CRs. These data support fascin inhibition as a novel DC-activating immunotherapy backbone for immune-resistant CSCC. Clinical trial information: NCT05023486 .

Neoadjuvant atirmociclib plus letrozole versus letrozole alone in HR+/HER2− breast cancer: Results from FourLight-2, a randomized phase 2 window of opportunity study.

518 Background: In the neoadjuvant setting, endocrine therapy is a standard of care option in patients (pts) with HR+ breast cancer (BC). Atirmociclib (ATI, PF-07220060) is a potent and selective CDK4 inhibitor and has shown favorable tolerability and promising early activity as a first-line treatment in pts with HR+/HER2− metastatic BC. CDK4 selectivity is hypothesized to limit hematologic and gastrointestinal toxicities that may be dose-limiting; therefore, ATI may improve efficacy and tolerability. Ki-67 is a biomarker used to assess the antiproliferative activity of therapies. Complete cell cycle arrest (CCCA, defined as Ki-67-positive tumor cells ≤2.7%) in the neoadjuvant setting is correlated with less BC tumor recurrence. This phase 2 randomized global study evaluated the effects of ATI + letrozole (LET) and LET alone on Ki-67 expression in HR+/HER2− BC tumors after 14 days of treatment in the neoadjuvant setting (FourLight-2; NCT06465368). Methods: Postmenopausal women with HR+/HER2− BC and Ki-67 score of ≥10% per local assessment, primary tumor ≥1.5 cm, no prior systemic therapy for BC, and ECOG PS ≤1 were enrolled. Eligible pts were randomly assigned to ATI (300 mg, orally BID) + LET (2.5 mg, orally QD) or LET alone (2.5 mg, orally QD), for 14 days. Baseline breast lesion biopsy and on-treatment biopsy on day 14 were obtained. The primary endpoint was centrally-assessed CCCA rate at day 14; secondary endpoints included Ki-67 expression change, safety, ctDNA assessments, and PK. Results: 121 pts were randomized to ATI + LET (n = 59) or LET alone (n = 62) arms; median age was 66 y and 63 y; 90% and 92% had Stage I/II disease, respectively. In Ki-67 evaluable pts (n = 51 and n = 56), 77% and 70% had Ki-67 ≥20% at baseline (centrally assessed) and 71% and 80% had grade 1/2 tumor, respectively. At day 14, the proportion of pts who achieved CCCA was 88.2% (95% CI, 76.6–94.5) for ATI + LET and 17.9% (95% CI, 10.0–29.8) for LET alone, with median relative change of Ki-67 from baseline of -97.3% (range -99.8%, 34.0%) and -72.4% (range -98.3%, 139.9%) in each arm, respectively. CCCA was achieved at a higher rate with ATI + LET than LET alone across baseline subgroups (Table). The most common TEAEs with ATI + LET and LET alone, respectively, were diarrhea (19% and 2%), fatigue (15% and 10%), and nausea (14% and 5%) (all grade 1/2); no grade 3/4 treatment-related TEAEs or treatment discontinuations due to TEAEs were reported. Conclusions: ATI + LET demonstrated substantially greater antiproliferative effects than LET alone, with a tolerable safety profile in pts with HR+/HER2− BC, suggesting that ATI + LET may have value in early BC. Clinical trial information: NCT06465368 . Subgroup Analysis with CCCA, n (%) ATI + LETn = 51 LET alonen = 56 Tumor grade 1/2 32 (89) 9 (20) 3/X 13 (87) 1 (9) Primary tumor stage T1c 12 (80) 2 (11) T2 28 (93) 7 (22) T3/T4 5 (83) 1 (20) Baseline Ki-67 (central assessment) <20% 9 (90) 4 (27) ≥20% 35 (90) 6 (15)

Treatment strategies in metastatic NSCLC after progression to immuno-chemotherapy: A random-effects network meta-analysis of phase III trials.

e20509 Background: Patients with metastatic non-small cell lung cancer (mNSCLC) progressing after immunotherapy (IO) plus chemotherapy have limited options, and the relative survival benefit of 2L+ strategies remains uncertain. A network meta-analysis (NMA) was performed to assess survival outcomes and rank experimental treatments versus standard of care in biomarker-unselected 2L+ mNSCLC. Methods: We leveraged LARVOL CLIN, an oncology outcomes database with 130k+ trials, 100k+ digitized Kaplan-Meier (KM) curves and 17k+ Hazard Ratios (HRs); to conduct a random-effects frequentist NMA. Pseudo-individual patient data (IPD) were reconstructed from published KM curves and at-risk tables using the Guyot algorithm. Trials were pooled by treatment arm and overall survival (OS) HR was estimated using Cox proportional hazards model. Results: Six phase III trials in biomarker-unselected 2L+ mNSCLC with progression after IO + chemotherapy were identified (Table 1). LEAP-008, SAPPHIRE, and CONTACT-01 evaluated IO-tyrosine kinase inhibitors (TKI); EVOKE-01 and TROPION-Lung01 TROP-2 antibody-drug conjugates (ADC); and LATIFY IO plus ATR inhibitor; all versus chemotherapy. LATIFY reported no OS benefit without published HR and was excluded from quantitative analyses. Across the remaining 5 trials, HR consistently favored experimental arms (OS 0.90 [0.82-0.99]; progression free survival (PFS) 0.87 [0.76-1.00]), with significant PFS benefit in CONTACT-01 and TROPION-Lung01. In the OS NMA, chemotherapy served as anchor. Treatments were ranked using p-scores, reflecting relative effectiveness with nivolumab- and atezolizumab-TKI ranking highest, followed by TROP-2 ADCs. Pembrolizumab-TKI and chemotherapy (0.2) ranked the lowest. No between-study heterogeneity or global inconsistency was observed (τ² = 0, Q = 0). In a pooled analysis of TROP-2 ADC trials, mOS was 12.03 and 10.48 months for chemotherapy (HR 0.91 [0.80–1.04]). Mechanism-specific grade ≥3 toxicities were observed across the 5 trials, including hypertension with IO-TKI and hematologic and gastrointestinal events with ADCs. Conclusions: This meta-analysis showed a modest trend towards improved OS and PFS for experimental treatments relative to standard of care chemotherapy. NMA ranked IO-TKI highest among the strategies, although caution is needed for cross-trial comparisons. These findings underscore the need for more effective strategies in 2L+ mNSCLC patients. Trials summary and NMA results. SAPPHIRE CONTACT-01 EVOKE-01 TROPION-LUNG01 LEAP-008 N 577 366 603 605 422 InterventionN Nivolumab + Sitravatinib284 Atezolizumab + Cabozantinib186 Sacituzumab Govitecan299 Datopotamab Deruxtecan299 Pembrolizumab + Lenvatinib185 OS HR 0.86 0.88 0.89 0.90 0.98 PFS HR 1.08 0.74* 0.92 0.75* 0.89 AE Gr3+% 49 vs 24 48 vs 46 54 vs 60 26 vs 42 60 vs 49 OS P-score 0.72 0.64 0.63 0.46

Early-onset <i>BRAF</i> -mutant metastatic colorectal cancer: A distinct clinical and molecular signature.

e15533 Background: BRAF V600E–mutant metastatic colorectal cancer (mCRC) is associated with poor prognosis and marked biological heterogeneity. Age at disease onset has emerged as a clinically relevant factor in colorectal cancer, but its influence on the biology of BRAF-mutant mCRC remains unclear. We examined whether early-onset (EO) and average-onset (AO) BRAF-mutant mCRC are biologically and clinically distinct subtypes. Methods: In a cohort of 1,209 metastatic colorectal cancer patients profiled by comprehensive next-generation sequencing and microsatellite stable (MSS), 234 BRAF V600E–mutant cases were identified. Patients were classified as early-onset (EO, ≤50 years; n = 73) or average-onset (AO, &gt; 50 years; n = 161). Clinical characteristics, primary tumor location, first-line treatment, tumor mutational burden (TMB), co-mutation profiles, and overall survival (OS) were compared. Results: EO and AO patients had similar sex distribution and performance status. Primary tumor location differed significantly: EO tumors were more frequently left-sided and rectal (left-sided 77.5%, rectal 57.1%), whereas AO tumors were predominantly right-sided (51.0%, p = 0.00017). EO patients more often received intensive first-line therapy (FOLFOXIRI ± anti-VEGF: 47.9% vs 29.2%, p = 0.0087), but despite more intensive upfront treatment, they experienced significantly shorter OS (median 18.5 vs 26.1 months; log-rank p = 0.048). Molecular profiling revealed marked differences. EO tumors had significantly lower TMB (median 6.2 mut/Mb, IQR 4.0–8.9) compared with AO tumors (median 9.8 mut/Mb, IQR 6.1–14.7; p &lt; 0.001) and fewer hypermutated cases. EO tumors were enriched for oncogenic alterations, including TP53 (82%), PIK3CA (48%), FBXW7 (26%) and PTEN (21%), consistent with a MAPK/PI3K-driven, genomically stable phenotype. In contrast, AO tumors showed higher frequencies of RNF43 (31%), APC (58%) and ARID1A (34%), consistent with a serrated, hypermutated molecular phenotype. Conclusions: Age at onset divides BRAF-mutant mCRC into two biologically and clinically distinct diseases. EO-BRAF tumours exhibit an oncogenic-driven, low-TMB profile associated with poorer survival despite more intensive chemotherapy, whereas AO-BRAF tumours show a serrated, hypermutated phenotype with longer survival. These findings emphasise intrinsic biological heterogeneity within BRAF-mutant mCRC and support age-informed molecular stratification in future clinical trials.

Targeted long-acting cisplatin–SRGel for enhanced chemoradiation in head and neck cancer: Preclinical pharmacokinetics, safety, and efficacy.

e18077 Background: Systemic cisplatin combined with radiotherapy is the standard of care for unresectable head and neck squamous cell carcinoma (HNSCC), but its use is often limited by severe toxicities, including nephrotoxicity, and neurotoxicity, etc. As a result, many patients, particularly elderly individuals and those with comorbidities, are ineligible for optimal cisplatin-based chemoradiation and receive less effective alternatives. Contrary to the numerous localized cisplatin delivery approaches that have been explored, SRGel is a solvent-free, lipophilic, biodegradable long-acting injectable platform enabling high local drug payloads with sustained release via surface erosion for approximately two months. SRGel -Cisplatin formulation of 100 mg/mL (10% w/w), termed TumoCure, was selected for translational development. This abstract summarizes the preclinical pharmacokinetics, safety, and efficacy of TumoCure as monotherapy and in combination with radiotherapy, compared with systemic cisplatin. Methods: TumoCure was studied for intratumoral applications, safety and efficacy. Pharmacokinetics and safety were evaluated in Sprague–Dawley rats following a single subcutaneous dose of TumoCure and compared with systemic cisplatin. Plasma platinum levels were measured by ICP-MS, and toxicity was assessed by clinical observations, blood chemistry, and histopathology. Antitumor efficacy was evaluated as monotherapy in FaDu HNSCC xenografts, and compared to systemic cisplatin. Combination efficacy was assessed in multiple HNSCC models with fractionated radiotherapy. Results: TumoCure produced approximately one order of magnitude lower peak systemic platinum levels than intravenous cisplatin, with prolonged exposure and reduced renal toxicity. Histopathology showed minimal foreign-body reaction at low and intermediate doses, while higher local doses produced localized necrosis consistent with on-target cytotoxicity. TumoCure achieved higher intratumoral platinum concentrations than systemic cisplatin and delayed tumor growth in selected HNSCC models. In combination studies, TumoCure plus radiotherapy produced superior tumor growth inhibition compared with radiotherapy alone or radiotherapy with systemic cisplatin, without the systemic toxicity associated with standard chemoradiation. Conclusions: TumoCure is a long-acting cisplatin formulation enabling sustained local drug exposure with markedly reduced systemic toxicity. Preclinical data demonstrate favourable pharmacokinetics, improved safety, and enhanced efficacy as monotherapy and in combination with radiotherapy compared with systemic cisplatin. TumoCure is currently being evaluated in a Phase Ib clinical study in palliative and resistant disease settings, with a Phase II combination study with radiotherapy in preparation.