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A URCC NCORP Research Base nationwide phase II randomized controlled trial (RCT) investigating the effect of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN).
12014 Background: Over 60% of patients with cancer receiving taxane, platinum, or other neurotoxic agents experience CIPN, which presents as numbness, tingling, and sometimes pain in the hands and feet. CIPN reduces quality of life and can increase mortality by limiting chemotherapy dose. With extremely limited treatments for CIPN, exercise has emerged as one of the most promising yet unproven treatments with no Phase III RCTs to date. Methods: This phase II RCT examines the effect of exercise on CIPN in the University of Rochester Cancer Center (URCC) NCI Community Oncology Research Program (NCORP) Research Base network, recruiting 111 patients across 37 community oncology practices spanning 11 states in the US. Key eligibility include receiving neurotoxic chemotherapy (taxane, platinum, vinca alkaloid, etc.) in the past 9 months and reporting symptoms of CIPN (≥ 4 of 10 at its worst in the past 2 weeks). Participants were randomized 1:1 to 6 weeks of usual care (UC) or virtually delivered Exercise for Cancer Patients (vEXCAP). vEXCAP is a virtually delivered, standardized, individualized, moderate-intensity, home-based, progressive walking and resistance exercise program. We assessed CIPN both pre- and post-intervention using patient-reported CIPN-20 (0-100 scale) and tactile sensitivity in the finger and toe using monofilaments. Each night, participants rated numbness/tingling in the hands/feet on a 0-10 scale. The primary outcome was CIPN-20 total score with CIPN-20 sensory and motor subscales as exploratory. Results: The 111 patients were 59.5 ±10.5 yrs, 76% female, 83% White, 37% breast cancer, 36% gastrointestinal cancer. Exercise yielded statistically and clinically meaningful improvements in CIPN sensory symptoms compared to UC (ΔCIPN-20 = -4.7 [MCID = 4], effect size [ES] = -0.27, p = 0.049). Exercise had a weak effect on CIPN motor symptoms (ΔCIPN-20 = 1.5, ES = 0.08, p = 0.936) and the CIPN-20 total score (ΔCIPN-20 = -1.2, ES = -0.07, p = 0.393). Tactile sensitivity was negatively correlated with CIPN sensory symptoms, as expected (finger: rho = -0.21, p = 0.043, toe: rho = -0.18, p = 0.092). Effects of exercise on tactile sensitivity were beneficial yet small and not statistically significant (ES = 0.04 and 0.07, both p > 0.682). Daily symptom ratings suggest that possible benefits of exercise emerge after 24 days (0.75±0.46 unit reduction, p = 0.104), with clear benefits after 30 days (0.93±0.46 unit reduction, p = 0.045) that grow further through study completion. Conclusions: Six weeks of walking and resistance exercise may reduce CIPN sensory symptoms for patients with CIPN. A future phase III RCT is needed to definitively test for replication and inform clinical practice. Funded by NCI: UG1CA189961, UG1CA189804, UG1CA189822, UG1CA189819, UG1CA189830, R21CA256154, and K07CA221931. Clinical trial: NCT04888988. Clinical trial information: NCT04888988 .
Histopathology-verified comparison of FET PET and contrast-enhanced MRI for tumor visualization in glioblastoma.
2049 Background: In glioblastoma, precise visualization is a prerequisite for optimal resection strategies and accurate radiotherapy volume definition. In routine practice, contrast-enhanced MRI (CE-MRI) is most commonly used; however, it can underestimate tumor extent when viable tumor is present without blood–brain barrier disruption and therefore without contrast uptake. The present study examined whether amino acid PET with O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) can better visualize the true distribution of tumor tissue and thereby improve preoperative assessment. Methods: In this prospective, biopsy-validated single-center study, in 61 patients with IDH-wildtype glioblastoma (44 newly diagnosed, 17 recurrent) 472 biopsies spatially correlated with preoperative FET PET and CE-MRI were histopathologically evaluated. Diagnostic metrics were calculated and compared between modalities using McNemar and Chi² tests (p = 0.05). Results: Overall, FET PET identified tumor tissue with significantly higher sensitivity than CE-MRI (91.2% vs. 55.7%; p < 0.001). When benchmarked against T2/FLAIR, FET remained more sensitive (85.3%; p = 0.012) while also demonstrating a pronounced gain in specificity (82.5% vs. 33.3%; p < 0.001). Remarkably, there was the high reliability of FET in regions without MRI contrast enhancement: biopsies taken from FET-positive areas without contrast enhancement showed a positive predictive value of 98.3%. Subgroup analyses consistently demonstrated the advantage of FET across clinical and histological strata, including newly diagnosed and recurrent disease (p < 0.001), as well as within cohorts with resection (p < 0.001; specificity p = 0.03) or biopsy (p < 0.001). Importantly, performance advantages were also observed regardless of histological tumor cell density, with FET exceeding CE-MRI in both histological strata (infiltration zone and solid tumor, both p < 0.001). Conclusions: FET PET demonstrated significant diagnostic superiority over CE-MRI for the visualization of glioblastoma tissue. Comparable positive predictive values in contrast-enhancing and non-enhancing regions indicate that FET PET detects tumor reliably, independent of the blood–brain barrier integrity. These findings support the integration of amino acid PET as an important component in target definition for both surgical and radiation planning in glioblastoma.
Early versus delayed oral feeding after esophagectomy for esophageal cancer: A systematic review and meta-analysis of randomized controlled trials.
e16027 Background: Postoperative oral intake after esophagectomy has traditionally been delayed due to concerns about anastomotic leakage. Although Enhanced Recovery After Surgery (ERAS) pathways increasingly support early feeding, its safety remains debated. This study compared early versus delayed oral feeding following esophagectomy for esophageal cancer. Methods: PubMed, Embase, and Scopus were systematically searched through October 2025 for randomized controlled trials evaluating early oral feeding (postoperative days 0–3) versus delayed feeding (postoperative day ≥5) after esophagectomy. Primary outcomes were anastomotic leakage and pneumonia. Secondary outcomes included postoperative complications, gastrointestinal recovery, length of hospital stay, healthcare costs, and quality of life. Pooled risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% confidence intervals were calculated using Review Manager 5.4. Results: Thirteen trials involving 1,468 patients were included. Early oral feeding was not associated with increased anastomotic leakage (RR: 0.89, 95% CI: 0.55–1.45; I² = 0%) and showed consistent safety across surgical approaches and anastomotic sites. The incidence of pneumonia was significantly reduced (RR: 0.66, 95% CI: 0.47–0.92; p = 0.01). Early feeding accelerated gastrointestinal recovery, including earlier first bowel movement (MD: −0.50 days, p < 0.00001) and passage of flatus (MD: −0.61 days, p = 0.0006). Hospital stay was shortened (MD: −1.89 days, p = 0.002), with lower medical costs (SMD: −1.19, p = 0.009). Quality-of-life measures improved, including global health status, dysphagia, pain, and swallowing function. Conclusions: Early oral feeding after esophagectomy appears safe and beneficial, reducing pulmonary complications and enhancing postoperative recovery. Further high-quality multicenter trials are needed to confirm these findings.
Intratumoral dendritic cell (DC1) therapy prior to neoadjuvant chemotherapy in HER2-positive breast cancer (NATASHA trial).
2594 Background: Enhancing the efficacy of neoadjuvant therapy (NAT) while minimizing treatment-related toxicity remains a critical unmet need for patients (pts) with HER2-positive (HER2+) breast cancer (BC). We previously reported intratumoral (IT) delivery of increasing doses (50 million and 100 million cells) of conventional type I dendritic cells (DC1) combined with anti-HER2 antibodies is safe and effective in altering the tumor microenvironment (TME) and inducing tumor regression in early-stage HER2+ BC. We conducted a phase II neoadjuvant clinical trial of IT DC1 (NCT05325632). Methods: Pts with early-stage HER2+ BC with tumor ≥ 1cm were eligible. Treatment included initial immunotherapy with IT DC1 weekly x6 (100 million) followed by paclitaxel 80 mg/m 2 IV weekly x12. Starting from day 1, pts also received trastuzumab (H) IV (8 mg/kg loading dose, then 6 mg/m 2 ) and pertuzumab (P) IV (840 mg loading dose, then 420 mg) every 3 weeks x 6 cycles. Core needle biopsies were obtained at baseline and at week 6 following the last DC1 injection and analyzed by multiplex immunofluorescence (mIF) to assess immune cell infiltration. At these timepoints and post-chemotherapy, radiologic response was assessed by breast MRI and blood was collected for biomarker and ctDNA analysis using a personalized, tumor-informed test (Signatera, Natera, Inc.). The primary end point of this study is pathologic complete response rate (pCR). Results: A total of 47 pts (24 HR+/HER2+, 23 HR-/HER2+) were enrolled between 5/2022 and 10/2025. Median age was 54 years (range 27-82). 21 pts had biopsy-proven axillary node positive disease with clinical stage I/II/III (7/30/10). All pts completed NAT, and 42 pts underwent surgery as of 1/22/2026. The pCR rates for HR+/HER2+ and HR-/HER2+ were 50% (12/24) and 89% (16/18), respectively. The most frequent toxicities related to DC1 were grade 1/2 chills, flu-like symptoms, headache, nausea, fever, and injection site reaction. IT DC1 + HP therapy was associated with a significant increase in intratumoral CD3⁺ T cell infiltration and a decrease in tumor cells assessed by mIF. ctDNA levels were evaluable for 25 patients (13 HR+ and 12 HR-). Sixteen pts (64%) had positive ctDNA (6 HR+ and 10 HR-) at baseline and 14/16 cleared ctDNA with NAT (13/16 cleared ctDNA post- IT DC1+HP, prior to chemotherapy). At present (median post-surgery follow-up: 15.1 mos.; median follow-up from last ctDNA test: 8.7 mos.), no pts have experienced disease recurrence. Conclusions: IT DC1 + HP prior to neoadjuvant paclitaxel + HP in HER2+ BC pts was well tolerated with manageable toxicities. IT DC1 led to immune cell infiltration and ctDNA clearance with improved pathologic tumor response rates, particularly in HR-/HER2+ BC. Updated surgical outcomes and biomarker results (mIF, MRI and ctDNA) will be presented at the meeting. Clinical trial information: NCT05325632 .
Sinonasal adverse events of immune checkpoint inhibitors: Pharmacovigilance using FAERS.
11146 Background: Immune checkpoint inhibitors (ICIs) are cancer therapies with diverse toxicities, known as immune-related adverse events (irAEs). Sinonasal irAEs have been described primarily in case reports, and their population-level characteristics remain poorly defined. To date, no statistical analysis of the FDA Adverse Events Reporting System Database (FAERS) has evaluated sinonasal adverse events (snAEs) associated with ICIs. Methods: We investigated snAEs associated with FDA-approved ICIs in FAERS between 1/1/2011 and 10/1/2025. ICIs were grouped by therapeutic target (PD-1, PD-L1, or CTLA-4). Analyses were conducted in R using Bioconductor package “faers”. Data were standardized using preferred term in the Medical Dictionary for Regulatory Activities and deduplicated based on concordance across drug, adverse event, and demographics. Disproportionality analysis used reporting odds ratio (RORs) in comparison with the overall FAERS database. We excluded adverse events with <2 reports. The study was created and reviewed by the authors prior to implementation. Results: 17 million FAERS reports were identified, of which 2,476 ICI-associated reports included snAEs. Two rare events demonstrated significant disproportionality among PD-1 inhibitors: chronic eosinophilic rhinosinusitis (n=3; ROR 7.71, 95% CI 2.34–25.42) and nasal mucosal hypertrophy (n=2; ROR 8.67, 95% CI 1.99 - 37.73). In contrast, more frequently reported snAEs including sinusitis, rhinorrhea, nasal congestion, anosmia, nasal polyps, paranasal sinus inflammation, parosmia, and rhinitis, were not overreported (Overall ROR 2.5 ≤1). Conclusions: In this large pharmacovigilance analysis snAEs were not broadly overreported after ICI therapy. Rare inflammatory phenotypes were disproportionately reported with PD-1 inhibition, suggesting an immune-mediated mechanism. Given the limitations of spontaneous reporting data and small event counts, these findings should be interpreted cautiously but highlight the need for increased clinical awareness and prospective studies to better characterize sinonasal immune-related toxicities. Sinonasal adverse events reported after ICI therapy. Adverse event Overall Freq Overall ROR (95% CI ROR 2.5 – ROR 97.5 ) CTLA 4 Freq CTLA4 ROR PD-1 Freq PD-1 ROR PD-L1 Freq PD-L1 ROR Anosmia 31 0.22 (0.15-0.32) 4 0.17 23 0.23 4 0.13 Chronic eosinophilic rhinosinusitis 3 7.71 (2.34-25.42) 0 0 3 10.56 0 0 Nasal congestion 157 0.2 (0.17-0.24) 15 0.12 122 0.23 20 0.13 Nasal mucosal hypertrophy 2 8.67 (1.99-37.73) 0 0 2 11.88 0 0.00 Nasal polyps 12 0.17 (0.09-0.33) 3 0.33 8 0.21 1 0.09 Paranasal sinus inflammation 4 1.96 (0.87-4.42) 0 3.69 3 2.23 1 1.44 Parosmia 48 0.52 (0.38-0.7) 9 0.64 37 0.63 2 0.11 Rhinitis 50 0.51 (0.39-0.68) 2 0.12 34 0.50 14 0.67 Rhinorrhoea 267 0.3 (0.27-0.35) 32 0.24 215 0.37 20 0.11 Sinusitis 300 0.21 (0.19-0.24) 56 0.27 204 0.22 40 0.14 Bold denotes statistical significance (ROR 2.5 >1).
Results of a phase II trial of nivolumab and ipilimumab in children and young adults with relapsed or refractory INI1-deficient cancers.
10029 Background: Several aggressive pediatric and young adult cancers are characterized by loss of INI1 expression, including malignant rhabdoid tumor, ATRT, epithelioid sarcoma and poorly differentiated chordoma. These cancers have a poor prognosis and limited effective treatments for relapsed or refractory disease. Prior data nominated immune checkpoint inhibition as a potential strategy for INI1-deficient tumors. Methods: In this phase II multicenter trial of nivolumab and ipilimumab, patients 6 months to 40 years with relapsed or refractory INI1-deficient cancers were enrolled in two strata: extracranial solid tumors (Stratum 1) and CNS tumors (Stratum 2). The primary endpoint was objective response ≥partial response (PR) by RECIST v1.1 (Stratum 1) or RANO (Stratum 2). Secondary endpoints included progression-free survival, overall survival and 12-month disease control rate. Patients received nivolumab 3mg/kg and ipilimumab 1mg/kg every 3 weeks for 4 cycles followed by nivolumab 3mg/kg every 2 weeks for up to 1 year. A Simon’s two-stage design targeted a response rate >25%, with each stratum assessed separately. Interim analysis at Stage 1 required ≥1 of 10 patients to have response ≥PR to proceed to Stage 2; at Stage 2, ≥3 of 20 patients with response ≥PR for evidence of efficacy. Evaluable patients received study treatment and were assessed for response or had progressive disease. Results: Thirty patients from six centers enrolled across both Strata from 8/2020 to 5/2025 and 27 were evaluable for the primary endpoint. Three inevaluable Stratum 1 patients were replaced per protocol. In Stratum 1, 1 patient (with poorly-differentiated chordoma) of 20 evaluable patients had ≥PR (ORR: 5%; 95% CI: 0.1-25%). In Stratum 1 (n=20), the 3-month EFS±SE and OS±SE were 20%±9% and 60%±11%, respectively, and the proportion of patients who were progression-free at 12-months was 5% (95%CI=0.1%-25%). Stratum 2 closed early with 7 patients enrolled, too few for Stage 1 interim analysis. No Stratum 2 patients had ≥PR [ORR: 0% (n=7)]. Patients received a median of 2 cycles of study treatment. The most common ≥ grade 3 treatment-related adverse events were decreased lymphocyte count (n=3), increased AST (n=3) anemia (n=2), and pneumonitis (n=2). Conclusions: The study did not meet the predetermined threshold for efficacy for Stratum 1. Immune checkpoint inhibitor therapy could warrant further exploration in poorly differentiated chordoma. Clinical trial information: NCT04416568 . Patient characteristics (n=27 evaluable patients). Median (Range) Age at enrollment (years) 7.1 (0.6-37.6) Lines of prior therapy 2 (1-7) n (%) Age group <18 yrs 24 (89%) ≥18 yrs 3 (11%) Sex Male 15 (56%) Female 12 (44%) Cancer diagnosis Stratum 1 20 (74%) Malignant Rhabdoid Tumor 12 (60%) Poorly Differentiated Chordoma 3 (15%) Epithelioid Sarcoma 2 (10%) Other 3 (15%) Stratum 2 7 (26%) Atypical Teratoid Rhabdoid Tumor 7 (100%)
Enhancing resident learning in anticoagulation management: A single-institution quality improvement study with comparison to large language models.
e23308 Background: Anticoagulation management is complicated by evolving guidelines and patient-specific factors, particularly in patients with cancer, pregnancy, and renal or hepatic dysfunction. This quality improvement initiative evaluated the impact of a structured educational intervention on resident anticoagulation knowledge and contextualized trainee performance using large language models (LLMs). Methods: We conducted a single-center quality improvement educational intervention involving Internal Medicine residents (PGY-1 to PGY-3). A 10-item multiple-choice questionnaire assessing anticoagulation stewardship in special populations was administered via REDCap before and after a guideline-based teaching session. Mean percent correct scores were calculated overall and for a prespecified subset of cancer-associated thrombosis questions. For comparison, two LLMs, ChatGPT and OpenEvidence, independently completed the same questionnaire before and after exposure to the educational material. Descriptive statistics were used. Results: 42 residents completed both assessments. Mean scores improved from 42.63% pre-intervention to 74.52% post-intervention, representing a 31.89 percentage point increase. Performance on cancer-associated thrombosis questions improved from 50% to 74.28%. ChatGPT and OpenEvidence each scored 80% on both pre- and post-intervention assessments, with no change in responses following exposure to the educational material. Incorrect responses did not overlap between the two LLMs. Both models provided reasoning, though only OpenEvidence cited peer-reviewed references. Conclusions: This intervention demonstrates that targeted, guideline-based anticoagulation education can produce clinically meaningful improvements in trainee knowledge, particularly in complex domains such as cancer-associated thrombosis. In contrast, the static performance of LLMs highlights their role as adjunctive tools rather than adaptive learners, underscoring the importance of structured medical education for clinical competency development. Pre- and post-intervention questionnaire results and comparison to LLMs. Pre-intervention % correct Post intervention % correct Absolute % Increase Answered correctly by ChatGPT Answered correctly by OpenEvidence 1. Provoked DVT 26.2 66.7 40.5 Yes Yes 2. Provoked PE 14.3 64.3 50.0 Yes Yes 3. ESRD, diagnosis of DVT 66.7 73.8 7.1 Yes No 4. Thrombophilia testing 26.2 83.3 57.1 Yes Yes 5. 3 rd trimester pregnancy, diagnosis of DVT 42.9 85.7 42.9 Yes Yes 6. Lung Cancer, eGFR > 60, diagnosis of DVT 64.3 92.9 28.6 Yes Yes 7. RCC, eGFR <30, diagnosed with VTE 28.6 47.6 19.0 No Yes 8. GI cancer, diagnosed with VTE 21.4 73.8 52.4 Yes No 9. HCC, VTE prophylaxis 52.4 61.9 9.5 No Yes 10. Breast Cancer, ambulatory, VTE prophylaxis 83.3 95.2 11.9 Yes Yes
Developing a pan-cancer foundation model for digital patient representation and clinical prediction across real-world oncology data.
e23012 Background: Foundation models in oncology (FM onc ) enable creation of unified digital patient representations that can adapt to diverse clinical and translational tasks. We developed a pan-cancer FM onc trained on large-scale real-world electronic health record (RWD) data and evaluated its utility across clinically relevant prediction tasks. Methods: The manually curated RWD Patient360 dataset, which included NSCLC, breast, colorectal, and prostate cancers, was used. FM onc is a time-aware Transformer-based model designed to capture longitudinal patient trajectories across visits. The model contains > 1.3B trainable parameters and a vocabulary of tokens representing clinical variables and allowable value classes, plus special tokens. Cohorts included NSCLC (N = 57,780), breast (N = 43,432), CRC (N = 18,521), and prostate cancer (N = 17,035), split into training (80%), validation (10%), and test (10%) sets. Masked-token self-supervised learning was used, with masking probability inversely proportional to variable prevalence to mitigate class imbalance. Trained FM onc embeddings were used as inputs to a lightweight XGBoost adapter for three downstream tasks: (1) mortality prediction, (2) cancer type classification, and (3) prediction of biomarker testing. Target events were excluded from inputs to prevent label leakage. Model performance was assessed using area under the curve (AUC) for binary outcomes and F1 score for multiclass tasks. Results: A total of ≈11.6M tokens (≈3850 tokens per patient) across 109,414 patients were used for FM training with convergence reaching 100 epochs. A NSCLC test set has the highest mortality rate of 66% while breast has the lowest with 22% and prostate and CRC ~40%. FM onc embeddings enabled high predictive performance across tasks. Test-set mortality prediction achieved across all cancer type AUC of 0.84-0.86. Cancer-type classification exhibited macro avg F1 of 0.98. Clustering embedding observed that breast and prostate are well separated in using LDA projection into 3D space while small overlap between CRC and NSCLC. In the biomarker testing task, FM onc embeddings accurately predicted testing utilization with macro-average F1 ≥0.95 across commonly ordered biomarkers, including NSCLC (e.g., EGFR, KRAS) and breast cancer (ER, PR, HER2). Lower performance (F1≈0.20–0.30) was observed for clinically selective, RNA-based genomic expression assays with low real-world utilization ( < 5%), reflecting sparse and site-dependent observation patterns in RWD rather than limitations of the learned patient representations. Conclusions: A pan-cancer FM onc trained on large-scale RWD generates compact digital patient representations that generalize across diverse downstream clinical tasks. The model demonstrates strong performance in survival-related prediction, cancer classification, and biomarker testing inference.
Phase 2 trial of TIL therapy for metastatic uveal melanoma: Evaluation of T cell potency and an in situ precision biomarker.
2512 Background: Uveal melanoma (UM) is a rare eye cancer that frequently metastasizes to the liver and responds poorly to systemic therapies. We previously reported that adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL) produced a 35% objective response rate (ORR) in metastatic UM, with infusion product tumor reactivity being the strongest predictor of response. To guide surgical harvest of metastases enriched for tumor-reactive TIL, we developed Uveal Melanoma Immunogenomic Score (UMIS), an in situ tumor transcriptomic biomarker. Here we present results of a phase 2 trial designed to validate the efficacy of TIL therapy in metastatic UM and prospectively evaluate predictors of response. Methods: In this single-center phase 2 trial (NCT03467516) metastatic UM patients underwent metastatectomy to generate early TIL cultures. Cultures demonstrating growth potential and autologous anti-tumor reactivity were expanded for infusion. Patients received non-myeloablative lymphodepletion with cyclophosphamide and fludarabine, followed by infusion of TIL and high-dose interleukin-2. The primary endpoint was ORR per RECIST v1.1. Exploratory analyses to identify response predictors were performed in the current cohort and a pooled dataset including the NCT01814046 cohort. Results: Thirty-three UM patients received TIL therapy. Most had high disease burden (82% M1b/M1c; 76% elevated LDH; 70% hepatic and extrahepatic metastases; 24% CNS), received a median of 2 prior metastatic treatments (64% checkpoint blockade, 33% tebentafusp), and had liver metastases as their TIL source (52%). Infusion products had a median of 5.24E10 TIL, were CD8-enriched (median 68%), and demonstrated autologous tumor reactivity in 61% (19/31). Among 32 evaluable patients, the ORR was 22% (7/32) with a median response duration of 10.8 months (maximum ongoing at 58 months). Tumor-reactive TIL conferred higher response rates (37%, 7/19) than nonreactive products (0%, 0/12; P = 0.026). Responders demonstrated higher persistence of infused TIL clones in peripheral blood (R/NR ratio = 10.69, P = 0.020). In the pooled cohort (n = 54, 52 evaluable), ORR was higher with reactive products (43%, 12/28) versus nonreactive products (0%, 0/20; P = 5.06E-4). UMIS of the source metastases predicted growth of tumor-reactive TIL cultures (Rho = 0.55, P = 2.72E-5), final infusion product reactivity (P = 0.040), and clinical response (P = 0.004). Conclusions: TIL therapy demonstrates clinically meaningful activity in advanced, pretreated metastatic UM. Infusion product tumor reactivity was the strongest predictor of response. UMIS identified metastases enriched with tumor-reactive TIL and predicted final product potency and clinical outcome. These findings support implementation of UMIS as a minimally invasive precision biomarker to guide patient and tumor selection for optimal therapeutic benefit. Clinical trial information: NCT03467516 .
First-line (1L) divarasib plus pembrolizumab (pembro) in advanced or metastatic <i>KRAS</i> G12C+ non–small cell lung cancer (NSCLC): Results from the Krascendo-170 study.
8510 Background: Krascendo 170 (NCT05789082) is an open-label, phase Ib/II, dose-finding and -expansion study of divarasib, an oral next-generation KRAS G12C inhibitor, with/without other anti-cancer therapies in 1L KRAS G12C + NSCLC. We report the primary analysis for pts receiving divarasib plus pembro in the programmed death-ligand 1 (PD-L1)-positive cohort (tumor cell [TC] ≥1%; cohort A1) and key preliminary data for the PD-L1-negative cohort (TC <1%; cohort A2). Methods: Eligible pts were aged ≥18 years with untreated advanced or metastatic KRAS G12C + NSCLC and ECOG PS ≤1. All pts received oral divarasib once daily plus intravenous pembro 200 mg once every 3 weeks until loss of clinical benefit, disease progression, study withdrawal or unacceptable toxicity. In cohort A1, pts were randomized 1:1 to receive divarasib 200 or 400 mg. In cohort A2, all pts received divarasib 400 mg. We present data only from pts receiving divarasib 400 mg. Primary endpoints were safety and tolerability. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and duration of response (DOR; all investigator-assessed per RECIST v1.1). Results: At data cutoff (Oct 29, 2025), 59 pts were enrolled to receive divarasib 400 mg in cohort A1 and 23 pts in cohort A2. In cohort A1 (median duration of divarasib treatment 10.6 months [range 0.3–24.3]), treatment-related AEs (TRAEs; divarasib- or pembro-related) were reported in 98% of pts; 65% of pts had grade (gr) 3/4 TRAEs and 0% had gr 5 TRAEs (Table). The most common TRAEs were diarrhea (75%; gr 3/4 16%), nausea (64%; gr 3/4 2%), vomiting (49%; gr 3/4 2%), ALT increase (49%; gr 3/4 20%) and AST increase (47%; gr 3/4 18%). In cohort A1, confirmed ORR was 73%, no patients had progressive disease as their best response, median DOR was not reached and median PFS was 19.3 months (95% CI 12.4–not estimable [NE]). In cohort A2 (median duration of divarasib treatment 2.8 months [range 0.5–8.8]), TRAEs were reported in 100% of pts (65% gr 3/4; 0% gr 5) and unconfirmed ORR was 70%. Conclusions: In Krascendo 170, divarasib 400 mg once daily plus pembro had a manageable safety profile. Promising efficacy was shown in pts with advanced KRAS G12C + NSCLC in both PD-L1- positive and -negative cohorts. A global, phase III trial investigating divarasib 400 mg in 1L advanced KRAS G12C + NSCLC (Krascendo 2; NCT06793215) is currently enrolling. Clinical trial information: NCT05789082 . Cohort A1, n=59* ,† Cohort A2, n=23 Median follow-up, months 12.2 3.4 Safety, n (%)Any gr TRAEGr 3/4 TRAE / serious TRAETRAE leading to Dose reduction / interruption Discontinuation 54 (98)36 (65) / 19 (35)28 (51) / 40 (73)14 (25) 23 (100)15 (65) / 3 (13)13 (57) / 14 (61)3 (13) ORR, % (95% CI) 73 (60–84) 70 ‡ (47–87) Median PFS, months [95% CI] 19.3 [12.4–NE] – *3 pts did not receive treatment, 1 pt received divarasib 200 mg; † safety analysis comprised all pts treated with divarasib 400 mg (n=55); ‡ unconfirmed.
Translating meta-analytic risk into absolute survival: Projection modeling of secondary-type mutations in ELN-favorable NPM1-mutated acute myeloid leukemia.
e18536 Background: Nucleophosmin 1 (NPM1) mutation is traditionally associated with a favorable prognosis in acute myeloid leukemia (AML), leading to classification of these patients within the European LeukemiaNet (ELN) favorable risk group. However, emerging evidence indicates that co-occurring secondary-type mutations (STMs), including ASXL1 , RUNX1 , EZH2 , and SRSF2 , may substantially modify this prognosis. While meta-analyses have quantified the relative risk associated with STMs using hazard ratios, the corresponding absolute survival impact remains unclear, limiting clinical interpretability and decision-making. Methods: We performed meta-analysis–based projection modeling using pooled overall survival hazard ratios reported in a recent systematic review and meta-analysis of 4,022 NPM1-mutated AML patients. For the ELN-favorable subgroup, the pooled hazard ratio for overall survival associated with STMs (HR 1.95; 95% CI 1.39–2.73) was combined with externally derived baseline 5-year survival estimates under a proportional hazards framework. Absolute survival probabilities were calculated using established survival–hazard transformations, and results were translated into projected outcomes for a hypothetical cohort of 1,000 future ELN-favorable NPM1-mutated AML patients. Uncertainty was quantified using the meta-analytic confidence interval. Results: Assuming a baseline 5-year overall survival of 70% for ELN-favorable NPM1-mutated AML patients without STMs, the presence of STMs was projected to reduce 5-year survival to approximately 50%. Based on the confidence interval of the pooled hazard ratio, projected survival with STMs ranged from 38% to 61%. In a simulated cohort of 1,000 patients, this corresponds to approximately 300 deaths at 5 years in the absence of STMs versus 501 deaths in the presence of STMs, yielding an estimated 200 excess deaths per 1,000 patients (plausible range: 90–320 excess deaths). These findings were robust across visualizations including absolute survival projections, stacked outcome distributions, and excess mortality estimates. Conclusions: Meta-analysis–based projection modeling demonstrates that secondary-type mutations may negate much of the favorable prognosis traditionally attributed to ELN-favorable NPM1-mutated AML, translating into a large absolute survival decrement in future patient cohorts. Converting relative risk estimates into absolute survival and event projections provides clinically actionable insight and supports the incorporation of secondary-type mutation status into risk stratification, trial design, and therapeutic decision-making.
Exploring diversity and composition of sulfidogenic gut bacteria in breast cancer.
574 Background: Sulfidogenic bacteria produce hydrogen sulfide, the excess of which is genotoxic and proinflammatory and is absorbed through the GI tract into the systemic circulation. The role of sulfidogenic bacteria in BC has not been explored. In this study, we aimed to evaluate sulfidogenic bacterial abundance and diversity in BC. We hypothesized that there will be lower alpha and beta diversity in BC groups. We also hypothesized that there will be a higher relative abundance of sulfidogenic bacteria in BC vs. controls. Methods: We used high throughput sequencing of the dsrA gene in stool samples of female participants with BC and controls without BC (n=283). Controls were further delineated into normal mammogram, abnormal mammogram with no evidence of BC (e.g. cysts, etc), and controls without BC but with a first degree relative who has BC. To process the sequences, QIIME2 bioinformatics pipelines were used with taxonomy assigned using the SILVA database. We performed alpha diversity analyses with nonparametric statistics, and beta diversity analyses using the Bray-Curtis and weighted/unweighted UniFrac metrics. Differential abundance of sulfidogenic bacteria at the genus level was calculated in R using the DESeq2 package. In the same samples, we used sequencing of the V3-V4 region of the 16s rDNA gene to compare relative abundance of total sulfidogenic bacteria between BC samples and controls in R using the DESeq2 package. Results: Using the Chao1 metric, we found higher sulfidogenic alpha diversity in BC vs. all controls (p < 0.001), BC vs. controls who have a first degree relative with BC (p = 0.005). as well as within controls with a normal mammogram vs. abnormal mammogram without BC (p = 0.037). We did not find significant differences in beta diversity between BC vs. controls. When analyzed visually using PCoA of unweighted UniFrac distances, there were two clusters within all patient groups, indicative of two enterotypes across all subjects. We did not find a significant difference in the relative abundance of overall sulfidogenic bacteria as identified by the 16S rDNA gene between BC and controls. However, Desulfovibrio was enriched in BC compared to normal mammogram samples with a log fold change of 1.69 (p = 0.013). Conclusions: These results suggest altered sulfidogenic gut bacterial community composition in individuals with BC, particularly in organisms with lower relative abundance. Desulfovibrio appears as a predominating organism in BC. This is supported by prior research, which suggests Desulfovibrio becomes less abundant in participants exposed to agents that inhibit BC cell proliferation. We propose that there are two enterotypes of sulfidogenic gut bacteria in women.
Efficacy and safety of QL1706-based combination therapy in recurrent or metastatic endometrial carcinoma previously treated with chemotherapy and immune checkpoint inhibitors: A single-arm, prospective, phase II trial.
TPS2694 Background: Patients with advanced endometrial cancer who have progressed after platinum-based chemotherapy and immune checkpoint inhibitors have limited subsequent treatment options and a very poor prognosis. Iparomlimab and tuvonralimab injection (QL1706) is a bifunctional combination antibody targeting both programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), developed using the MabPair biotechnology platform. This study aims to evaluate the efficacy and safety of QL1706 combined with chemotherapy ± bevacizumab in patients with recurrent or metastatic endometrial cancer previously treated with immune checkpoint inhibitors. Methods: In this prospective, single-arm, multicenter phase II clinical trial, up to 30 participants will be enrolled. Eligible patients must be aged ≥18 years, have an Eastern Cooperative Oncology Group Performance Status score of 0 to 1, be diagnosed with recurrent or metastatic endometrial carcinoma, have previously received PD-(L)1 therapy for over 6 months, and have experienced disease progression during or after prior chemotherapy and PD-(L)1 targeted therapy. Up to two prior lines of systemic therapy are permitted. Patients who previously received PD-(L)1 plus CTLA-4 targeted therapy or discontinued anti-PD-1/PD-L1 antibody therapy due to related toxicities are excluded. Enrolled patients will receive QL1706 (5 mg/kg every 3 weeks) combined with chemotherapy (investigator’s choice, administered for 3–6 cycles) ± bevacizumab (15 mg/kg every 3 weeks) until disease progression, unacceptable toxicity, or other protocol-specified termination events. The primary endpoint is the objective response rate (ORR) as assessed by the investigator according to RECIST v1.1. Secondary endpoints include progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety. As of January 2026, 5 of the planned 30 patients have been enrolled. Clinical trial information: NCT06917092 .
Real-world patterns of hyperlipidemia and cardiometabolic toxicity in patients with ALK-fusion– positive NSCLC treated with lorlatinib.
e20724 Background: Lorlatinib is highly effective for ALK-rearranged NSCLC but is associated with hyperlipidemia (HLD) and metabolic complications. Real-world data on the severity, timing and management of cardiometabolic consequences remain limited. Methods: Patients (pts) with ALK-rearranged NSCLC treated with lorlatinib at Rush University Medical Center from 2017–2025 were identified via prescription records. Clinical and laboratory data, including lipid profiles and lipid-lowering therapy use or intensification, were collected to identify severe HLD and cardiovascular events. Protocol was approved by IRB. Results: Thirty-seven pts started lorlatinib with median age of 59.8 years. Most were White (n=22, 59.5%) and had never used tobacco (n=25, 67.6%); 18 (48.6%) were female. Eleven pts died during the assessment period. Among pts with baseline or first on-treatment lipid values ≤14 days, HLD occurred early (median 85 days, table); total cholesterol (CHL) and LDL increased within 2–12 weeks (median change +60.5 mg/dL and +58.0 mg/dL respectively). Triglycerides (TG) increased from 131 to 258 mg/dL (median +136 mg/dL; p=0.04) while HDL remained stable. LDL showed a significant time-dependent increase of 32.9 mg/dL per 4 weeks (95% CI 16.5–49.3; p<0.001) in the first 3 months. CHL, TG and HDL showed greater variability with non-significant slopes. Among pts not on baseline lipid-lowering therapy, 17.2% (n=5) initiated statins within 90 days; PCSK9 inhibitors were used in 4 (10.8%). Coronary events (CAD/MI) and stroke/TIA occurred in 9 and 11 pts respectively. HLD frequently co-occurred with stroke/TIA (p=0.02, OR 5.8). Conclusions: Lorlatinib was associated with early, clinically meaningful increases in atherogenic lipids, particularly LDL, with delayed vascular and cardiac complications. Lipid derangements may be associated with downstream cerebrovascular risk, supporting early and systematic lipid monitoring with proactive cardio-oncology–guided risk mitigation. Analyte Paired N Baseline Median (IQR), mg/dL 2–12 Week Median (IQR), mg/dL Median Change (IQR), mg/dL Wilcoxon p-value Mixed-Effects Change per 4 Weeks (95% CI), mg/dL Mixed-Effects p-value Total Cholesterol 8 185 (178.2–217.8) 241.5 (209.5–313.2) +60.5 (−3.8 to 130.5) 0.24 +30.1 (−18.3 to 78.7) 0.22 LDL 5 111 (88–116) 152 (151–210) +58 (35–99) 0.13 +32.9 (16.5 to 49.3) <0.001 Triglycerides 8 131 (95.8–212.3) 258.5 (190.8–351) +136 (28.5 to 253) 0.04 +121.1 (−50.5 to 292.8) 0.17 HDL 8 49.5 (41.8–57.5) 47 (40.8–52) −2.5 (−8.3 to 4) 0.8 −1.1 (−6.3 to 4) 0.67 Outcome Baseline diagnosis n/N (%) Incident after lorlatinib n/N (%) Median time to incident days (range) Hyperlipidemia 10/37 (27.0%) 13/27 (48.1%) 85 (25–350) Coronary event 5/37 (13.5%) 9/32 (28.1%) 356 (27-2092) Stroke/TIA 10/37 (27.0%) 11/23 (47.8%) 301 (18–1619) Peripheral arterial disease 5/37 (13.5%) 2/32 (6.2%) 748 (136–1360)
Reducing oncology transportation burden with decentralized treatment trials.
e23003 Background: Poor accrual to oncology treatment trials due to numerous factors, including patient burden, has been well documented. The University of Chicago (UCM) has decentralized treatment trials by allowing consent, enrollment and treatment at eight locations across Chicagoland where UCM clinical services are available (referred to as a network location). The purpose of this assessment was to determine the impact of decentralizing oncology treatment trials on two aspects of transportation burden (miles saved and cost saved in dollars) for patients participating in UCM treatment trials at a network location. Methods: In fiscal year 2025, 155 patients were enrolled on a treatment trial at a UCM network site. Miles saved was calculated as (M-N)*T, where M = roundtrip distance from patient’s home to main campus, N = roundtrip distance from patient’s home to network location and T = number of treatment visits required per trial during FY25. Dollars saved was calculated by multiplying miles saved by 70 cents (the national reimbursement rate). Mean values for miles and dollars saved was computed for hypothesis testing. The null hypothesis is that zero miles and zero dollars are saved by patients being enrolled at UCM’s main campus. Results: 90% of patients evaluated received care at a location that was closer to home (interestingly, 10% chose to receive care at a network location despite the main campus being closer). Total miles saved for evaluated patients was 47,261 (with a mean of 304.9 miles per patient). Total dollars saved was $33, 082. 56 (with a mean of $213.44 per patient). Compared to the null hypothesis, both miles and dollars saved are statistically significant at p=.0001. Conclusions: Data showed that opening treatment studies closer to patient’s home can reduce miles travelled, financial toxicity and overall patient burden. The current analysis focused only on treatment visits required by protocol; but many patients must complete visits outside of treatment visits (labs, imaging, clearance visits requested in advance of a treatment visit, research blood/biopsy visits, and more). Other financial burdens like parking, tolls, traffic, time away from work and caregiver time were not taken into consideration. This analysis provides quantitative information needed to bolster the assumed benefits of decentralization. Further analysis of total patient visits over the course of treatment and associated time toxicity savings are needed.
Targeting stromal FAK signaling to address chemotherapy and immunotherapy resistance in gastric-type endocervical adenocarcinoma.
5524 Background: Gastric-type endocervical adenocarcinoma (GAC) is a rare, HPV-independent cervical cancer subtype with profound resistance to standard chemotherapy and radiotherapy and an exceptionally poor prognosis. Unlike HPV-associated cervical cancers, GAC lacks established molecular targets and effective treatment strategies. Whether patients with GAC can benefit from immunotherapy remains unclear, and the biological mechanisms underlying its intrinsic resistance to both cytotoxic and immune-based therapies are poorly understood. Methods: We established an integrated translational platform incorporating patient-derived GAC cell lines, organoids, and matched primary cancer-associated fibroblasts (CAFs). These models were integrated with multi-omics profiling of clinical specimens, including single-cell RNA sequencing of 58 cervical lesions across disease states, together with molecular and functional validation assays, to systematically characterize tumor–stroma interactions and identify actionable therapeutic vulnerabilities. Results: Multi-omics analyses revealed that GAC converges on a pancreatic ductal adenocarcinoma–like transcriptional and microenvironmental program characterized by stromal dominance and therapeutic refractoriness. Mechanistically, GAC tumor cells reprogram the tumor microenvironment through secretion of LAMA3, activating a CD44/ITGB1-dependent FAK signaling axis in CAFs. Stromal FAK activation drives extracellular matrix remodeling and endothelial dysfunction, establishing a profoundly immunosuppressive niche marked by impaired antigen presentation and enrichment of tissue-resident CD8 + T cells (CD8 + ITGA1 + ). This stromal program mechanistically underlies resistance to both chemotherapy and immunotherapy. In patient-derived GAC organoid-based models, FAK inhibition enhanced responses to chemotherapy and immunotherapy in vitro, supporting a translational rationale for FAK-targeted combination strategies. Based on these findings, we initiated a multicenter, phase II clinical trial evaluating the FAK inhibitor IN10018 in combination with nab-paclitaxel and cadonilimab in patients with metastatic, recurrent, or persistent GAC (NCT06654011). Conclusions: Gastric-type endocervical adenocarcinoma is a stroma-driven malignancy in which aberrant stromal FAK signaling is a central mediator of resistance to both chemotherapy and immunotherapy. Targeting this stromal dependency provides a compelling therapeutic strategy and directly informs an ongoing phase II clinical trial addressing a critical unmet need in this aggressive disease.
Identification of tumor repopulating–like epithelial cells and a repair-dominant niche in pathological responders after neoadjuvant chemo-immunotherapy for HNSCC.
6070 Background: Neoadjuvant PD-1 blockade plus chemotherapy can induce deep pathologic responses in HNSCC. However, pCR is an imperfect surrogate for OS, and the prior study showed that >50% of patients achieving CR after neoadjuvant chemo-immunotherapy relapse rapidly without local therapy, suggesting post-treatment ecosystems may retain programs supporting residual cell persistence and relapse. Methods: We profiled tumors from treatment-naïve patients and from patients receiving neoadjuvant taxane/platinum (TP) plus PD-1 blockade with partial response or pCR using scRNA-seq and Xenium spatial transcriptomics. Integrated computational analyses mapped residual epithelial/microenvironmental programs and spatial organization, with validation by immunoblotting, flow cytometry, and mIHC. Translational strategies were evaluated in a 4NQO-induced murine model and a PD-1–resistant murine tongue cancer line. Results: We identified a KRT15+IL1R2+ stem-like epithelial population enriched after therapy, most prominent in pCR (61/78 patients), localized to post-treatment regression beds but not discernible on H&E. They were viable and quiescent, lacking DNA damage and cell-death activation; CytoTRACE indicated high differentiation potential, suggesting tumor-repopulating cells. Concerning the microenvironment, across the response continuum from treatment-naïve to partial pathologic response to pCR, scRNA-seq revealed stepwise enrichment of infiltrating non-exhausted cytotoxic CD8 effector T cells, consistent with progressively strengthened tumoricidal immunity. In contrast, deep responders displayed a shift toward a repair-dominant niche: macrophages progressively transitioned from CXCL9+ inflammatory monocytes to SPP1+ macrophages with reduced antigen-presentation programs and enhanced tissue-remodeling features, accompanied by enrichment of multiple repair-associated fibroblast states. Xenium further supported spatial proximity and putative interactions among IL1R2+ epithelium, macrophages, and fibroblasts, which may limited T cell–tumor contact. IL1R2 upregulation was also observed in a PD-1–resistant murine tongue cancer line. In vivo, IL-1β co-administration with PD-1 blockade attenuated treatment efficacy, whereas anti–IL-1β antibody combined with PD-1 blockade enhanced efficacy. Conclusions: Deep responses to neoadjuvant chemo-immunotherapy are coupled with a paradoxical repair program and enrichment of IL1R2+ stem-like epithelium that may permit residual persistence and recurrence. The IL-1β–IL1R2 axis is a translationally actionable lever to improve durability and mitigate relapse. Given residual risk even after pCR, de-escalation of local therapy (such as reducing surgical extent or altering definitive treatment strategies) warrants caution.
Ligand‐Switched Regiodivergent Fluoroallylic Alkylation of Secondary Nitroalkanes via an Unusual Inner‐Sphere Pathway
ABSTRACT As one of the cornerstones of modern organic synthesis, the Tsuji–Trost reaction is fundamentally governed by the “hard–soft” characteristics of nucleophiles, which confine nitroalkanes as “soft” pronucleophiles to classical outer‐sphere substitution pathway. Here we report a palladium‐catalyzed fluoroallylic alkylation of secondary nitroalkanes with gem ‐difluorocyclopropanes that overturns this long standing reactivity paradigm by enabling their engagement through an inner‐sphere pathway. This strategy enables the switchable regiodivergence between linear and branched allylic nitroalkanes—an outcome unattainable under classical Tsuji–Trost conditions and unprecedented for secondary nitroalkanes. This method exhibits excellent functional‐group and heterocycle tolerance and is readily applicable to the late‐stage modification of structurally complex bioactive molecules. Moreover, its synthetic utility has been further highlighted by various downstream derivatizations of the resulting 2‐fluoroallylic α ‐tertiary nitroalkanes. DFT studies indicate that ligand‐controlled oxygen coordination to electrophilic fluoro‐π‐allyl–Pd intermediates enables an inner‐sphere 3,3'‐reductive elimination, thereby accounting for the excellent regioselectivity in C(sp 3 )–C(sp 3 ) bond formation.
Zinc‐Doping Trap Engineering and FRET Synergy Enable Multicolor Room‐Temperature Phosphorescence in Rice‐Derived Carbon Dots Confined in Amorphous Alumina for Advanced Encryption
ABSTRACT The development of multicolor room‐temperature phosphorescence (RTP) materials with tunable afterglow is crucial for advanced information encryption. Herein, we propose a synergistic strategy that integrates trap engineering and Förster resonance energy transfer (FRET) process for dynamically adjusting the emission color and lifetime. Expired rice‐derived carbon dots@Zn‐doping alumina (CDs@Zn x Al 2 O 3 ) composites with standout RTP properties are designed and fabricated using an in situ preparation strategy. In situ Zn 2+ doping is employed to engineer trap states within amorphous Al 2 O 3 , which not only optimizes the energy level structure of confined CDs but also enables precise modulation of phosphorescence color and lifetime. The optimized CDs@Zn 1.5% Al 2 O 3 composite achieves an ultralong green RTP duration of up to 22 s. Furthermore, by introducing newly synthesized red‐emissive TPA‐β‐CD‐aggregates with excellent aggregation‐induced emission (AIE) performance as an energy acceptor, efficient singlet‐to‐singlet and triplet‐to‐singlet FRET (SS‐FRET/TS‐FRET) pathways are established. Tuning the doping ratio allows dynamic control over the competition between these pathways, resulting in finely adjustable multicolor RTP emissions. This work demonstrates a versatile platform for creating color‐tunable, ultralong RTP materials and showcases their direct application in time‐gated, multilevel security encryption.
Enhanced Internal Magnetic Field for Long‐Cycle NCM‐Li All‐Solid‐State Batteries via Dual‐Inhibition of Anode Dendrite and Cathode Cation Disorder
ABSTRACT Solid‐state batteries, which incorporate a Li metal anode and a high‐voltage Ni‐rich layered oxide (LiNi x Co y Mn 1–x–y O 2 , x ≥ 0.8) (NCM) cathode, offer the promise of high energy density for next‐generation batteries. Although solid‐state electrolytes are anticipated to enhance safety and performance over conventional liquid‐state electrolytes, they still fail to prevent non‐uniform lithium deposition on the anode surface. Moreover, while solid‐state electrolytes can partially suppress parasitic reactions at the cathode‐electrolyte interface, mitigating structural degradation caused by Li/Ni antisite disorder remains challenging. Herein, we demonstrate a two‐orders‐of‐magnitude enhancement in the internal magnetic field during battery cycling by incorporating Fe 3 O 4 nanorods within the solid electrolyte. The strengthened magnetic field alters the deposition behavior of lithium ions on the anode via the magnetohydrodynamic effect and, concurrently, suppresses the structural degradation of the cathode by regulating the spin state of Ni 3 + . The enhanced internal magnetic field applies throughout the entire life of the NCM||Li all‐solid‐state battery, improving its cycling stability. Unlike external magnetic fields, this internal approach requires no complex equipment and avoids integration challenges.