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Fruquintinib in combination with sintilimab and CAPEOX as first-line treatment for advanced gastric/gastroesophageal junction adenocarcinoma: A single-arm, open-label, multicenter phase Ib/II study (FUNCTION).

e16033 Background: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has become the standard first-line (1L) treatment for advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC), but the efficacy still needs to be improved. Fruquintinib, an oral and highly selective VEGFR 1/2/3 inhibitor, has shown a synergistic antitumour effect when paired with ICIs/chemotherapy. This study was aimed to evaluate the efficacy and safety of fruquintinib combined with CAPEOX and sintilimab as a 1L therapy in GC/GEJC. Methods: In this phase Ib/II trial, patients (pts) aged 18-75 years without prior exposure to anti-cancer treatment were enrolled. The Ib phase employed a 3+3 dose escalation design, pts were treated with fruquintinib 3mg/d, po, d1-14 (dose level; DL1), 4mg/d (DL2), or 5mg/d (DL3) in combination with fixed dose of sintilimab (200mg, iv, d1), oxaliplatin (130 mg/m 2 , iv, d1) and capecitabine (800 mg/m 2 , bid, po, d1-14) every 3 weeks. After up to 6–8 cycles, fruquintinib in combination with sintilimab would be administered as maintenance therapy. The primary objective of phase Ib was to determine the DLT in first treatment cycle defining the MTD and PR2D. Additional 61 pts were enrolled in the phase II dose expansion stage using RP2D. Primary endpoint of phase II was ORR per RECIST 1.1. Secondary endpoints included DCR, PFS, OS, DOR, surgical conversion rate, safety and identification of molecular biomarkers for efficacy. Results: At data cut-off (December 25, 2025), 24 pts (8 in phase Ib; 16 in phase II) had been enrolled. The pts were characterized with a median age of 59 years (range, 51-67), 45.8% GEJC, 75% lymph node metastasis, and 41.7% liver metastases. 20 pts had PD-L1 CPS available and 70% (14/20) were CPS ≥1, 30% (6/20) were CPS≥5. Two consecutive DLTs were observed at DL3, so DL2 was identified as MTD. Fruquintinib 4mg/d was defined as the RP2D. Of the 22 pts evaluable for tumor response, 18 pts achieved PR, 4 pts achieved SD. The confirmed ORR was 81.8%, the DCR was 100%. After a median follow-up of 17.74 months, the median PFS was 9.0 months (95% CI: 4.40–NA) and OS was not mature yet. Conversion surgery had been conducted in 4 pts after multidisciplinary team evaluation, with one case of pathological CR. The R0 resection rate was 100% (4/4) and R0 surgical conversion rate was 18.2% (4/22). Most TRAEs were grade 1-2 and grade 3/4 TRAEs occurred in 41.7% of pts, with platelet count decreased (12.5%) ranking the most frequent. There were no treatment related deaths in the trial. Conclusions: Fruquintinib plus sintilimab and CAPEOX showed encouraging clinical outcomes and manageable safety for untreated advanced GC/GEJC. The trial is still recruiting, more data including the subgroup analysis and potential predictive response biomarkers would be further analyzed and reported. Clinical trial information: NCT06329973 .

Clinical efficacy of a novel oral SERD TFX06 in prior fulvestrant-treated ER+/HER2− advanced breast cancer patients in a dose expansion study.

1062 Background: Patients with ER+/HER2- advanced breast cancer who have progressed on prior endocrine therapies, including fulvestrant, represent an area of unmet medical need, particularly those harboring ESR1 mutations. As far as we know, there was limited reports on efficacy of oral SERD in prior fulvestrant treatment progressed patients. TFX06 is an investigational next-generation oral SERD. Here, we report results from a Phase I/Ⅱ study of TFX06 in patients with ER+/HER2- advanced breast cancer who had progressed from prior fulvestrant treatment (NCT05927779). Methods: Eligible patients regardless of their menopausal status, who had received ≥1 lines of endocrine therapy (ET), prior fulvestrant (fulv) treated with or without CDK4/6i, and ≤2 line of chemotherapy in metastatic disease, were allowed to enroll. TFX06 tablets were orally administered at 150mg once daily (QD) in 28-day cycles until disease progression or intolerable toxicity. This analysis focuses on the subgroup with prior fulvestrant exposure. As of cut-off date December 22, 2025, 42 patients received TFX06 monotherapy at 150mg. Median age was 60.5 years (range, 34-73), 76.2% had an ECOG performance status of 1. 88.1% had visceral metastasis, and 16.7% had brain metastasis. The median number of prior endocrine therapies in the advanced or metastatic setting was 2 (range, 1-3), including fulvestrant (100%), CDK4/6i (85.7%) with combination (76.2%). Tumor assessments by investigators according to RECIST v1.1 were performed every eight weeks. Results: Of the 42 enrolled patients, 40 were evaluable for efficacy. In the full analysis set (n=40), median progression-free survival (PFS) was 5.5 months (95% CI, 3.2–7.8). The objective response rate (ORR) was 7.5% (3/40), disease control rate (DCR) was 60.0% (24/40), and clinical benefit rate (CBR) was 44.1% (15/34). In the ESR1-mutant subgroup (n=23), median PFS was 5.7 months (95% CI, 2.5–8.8), ORR was 8.7% (2/23), DCR was 65.2% (15/23), and CBR was 47.1% (8/17). Treatment emergent adverse events (TEAEs) occurred in 95.2% of patients (40/42), with grade ≥3 events in 26.2% (11/42). Most common TEAEs (≥20%) are laboratory abnormalities; they included hypertriglyceridemia (47.6%), increased AST (31.0%), anemia (31.0%), decreased lymphocyte count (23.8%), and decreased white blood cell count (21.4%). No TEAEs led to treatment termination. Conclusions: TFX06 showed promising clinical activity and a manageable safety profile in patients who progressed from prior fulvestrant-treatments including combination with CDK4/6i in ER+/HER2- advanced breast cancer, including those with ESR1 mutations. These findings support further development of TFX06 as a potential therapeutic option in this population. Clinical trial information: NCT05927779 .

A phase 2 study of fedratinib in patients with MDS/MPN and chronic neutrophilic leukemia.

6509 Background: MDS/MPNs are complex diseases that exhibit proliferative symptoms and aggressive clinical courses. Treatment options are limited. Ruxolitinib, a JAK1/JAK2 inhibitor, showed clinical benefit in pts with chronic neutrophilic leukemia (CNL) and atypical CML (aCML); yet survival remained poor (mOS 18.8 mo). Fedratinib (Fed) is a JAK2 inhibitor approved for MF that, compared to ruxolitinib, has a broader kinase inhibition profile which may provide enhanced efficacy in molecularly complex disease. Fed potently inhibits FLT3 and BRD4 and potently suppresses c-Myc, a critical upregulated pathway in MDS/MPN. Here, we present the primary results of NCT05177211 assessing the efficacy of Fed in pts with MDS/MPNs. Methods: NCT05177211 is a phase 2, multi-institutional study that enrolled pts with aCML, CNL, MDS/MPN-unclassifiable (MDS/MPN-U), and MDS/MPN-ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) who have splenomegaly (spleen volume > 450cc) and/or significant symptom burden (MPN TSS ≥ 10). The primary endpoint is overall response defined as complete/partial response or clinical benefit at 24 weeks per MDS/MPN IWG response criteria. Exploratory endpoints include progression-free survival (PFS), overall survival (OS), and duration of response (DOR). Fed was given at a dose of 400 mg daily on day 1-28 of 28-day cycles. Results: The data cutoff was 1/1/2026. Among 25 pts, 6 had aCML, 5 had CNL, 6 had MDS/MPN-RS-T, and 8 had MDS/MPN-U. Median age was 68.8 y. ≥3 mutations were present in 19 (76%) pts. Three (12%) pts remain on study. Median duration of treatment was 7.4 months. Eleven (44%) pts responded at week 24: 6 (30%) spleen responses (SVR35) and 9 (47%) symptom responses (TSS50). Four (25%) pts had both spleen and symptom response. Among 16 pts with splenomegaly treated for ≥ 24 weeks, spleen volume decreased by an average of 30% (+9% to -61%). Among 16 pts with symptomatic disease treated for ≥ 24 weeks, TSS improved by an average of -41% (range +35% to -80%). CSF3R mutations were enriched among pts with SVR35 (n = 4; 67%). Median PFS and OS were 36.9 mo (95% CI 19.3-NR) and 36.9 mo (95% CI 18.4-NR), respectively. Among responders, the duration of response was 7.6 mo (95% CI: 3.72-not reached). When stratified by diagnosis, OS for aCML, CNL, MDS/MPN-RS-T, and MDS/MPN-U was 19.8, 36.9, NR and NR, respectively. SAEs occurred in 13 (52%) pts. SAEs possibly related to Fed included acute kidney injury (n = 2), low thiamine (n = 1), colitis (n = 1), diarrhea (n = 1), arthralgias (n = 1), and edema (n = 1). Any grade nausea, vomiting, diarrhea, and constipation were seen in 52%, 16%, 44%, and 48% of pts, respectively. Conclusions: Fed demonstrates promising clinical efficacy in MDS/MPN and CNL pts with proliferative features. The safety profile is consistent with prior experience. Fed’s unique kinase inhibition profile may provide a mechanism for enhanced effectiveness in this pt population. Clinical trial information: NCT05177211 .

A phase II clinical trial of ivonescimab (VEGFxPD-1 bispecific antibody) in patients with metastatic castration-resistant prostate cancer (mCRPC).

TPS5138 Background: Patients with mCRPC achieve limited responses with single-agent immune checkpoint therapies (ICTs), due to tumor microenvironments (TME) characterized by few intratumoral effector T cells and high prevalence of suppressive myeloid cell populations, cytokines, and signaling pathways. In murine models of mCRPC, tyrosine kinase inhibitors (TKIs, i.e. against vascular endothelial growth factor [VEGF] receptor 2, MET, and AXL, among others) inhibited tumor infiltrating myeloid-derived suppressor cells and enhanced responses to ICTs (Lu X et al., Nature 2017). Consistent with this, a phase III clinical trial combining TKI and anti-PD-(L)1 demonstrated improved clinical outcomes in a subset of patients with mCRPC (Agarwal N et al., Lancet Oncol 2025). Ivonescimab is a first-in-class bispecific antibody simultaneously targeting PD-1 and VEGF-A that has demonstrated clinical activity across multiple tumor types. We hypothesized that ivonescimab will induce anti-tumor responses in a subset of patients with mCRPC. Methods: This is an open-label, single-center phase II clinical trial in patients with mCRPC with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology. The primary endpoint of the study is objective response rate per Prostate Cancer Working Group 3 (PCWG3) criteria, and secondary endpoints include duration of response (DOR), disease control rate (DCR) greater than 6 months), radiographic progression free survival (rPFS), PSA 50 responses (defined as confirmed > 50% decline in PSA from baseline) and incidence, severity, and duration of adverse events. Tumor biopsies are collected at baseline and prior to C2D1 for evaluation of biomarkers of response and resistance to therapy. The study is being conducted using a Bayesian optimal phase 2 (BOP2) design. A total of up to 24 patients will be enrolled on study. The study is currently open and enrolling (NCT06567314). Clinical trial information: NCT06567314 .

Longitudinal palliative care delivery in oncology in a resource-constrained setting: Experience from 1,500 patients in Albania.

e24077 Background: Early integration of palliative care is a core component of high-quality oncology care; however, access and structured integration remain limited in resource-limited settings. In Albania, patients with advanced cancer frequently present with a high symptom burden and are often managed in emergency or intensive care units due to the lack of dedicated palliative care services, highlighting a significant gap in quality cancer care. Methods: We conducted a retrospective descriptive analysis of oncology patients longitudinally followed by the same medical oncologist between 2014 and 2025. A total of 1,500 patients receiving palliative-oriented oncology care were included. Data collected included primary tumor type and age-group distribution. Based on identified unmet needs, a pilot inpatient palliative care consultation service was designed at a tertiary university hospital in Albania. Results: Between 2014 and 2025, 1,500 patients were longitudinally followed within a palliative care framework. The most common tumor types were lung, gastrointestinal, breast, and genitourinary cancers, with representation of less frequent malignancies. The majority of patients were aged ≥65 years, reflecting a population with complex symptom burden, multiple comorbidities, and increased care needs. These findings identified critical gaps in inpatient symptom management and end-of-life care delivery. To address these gaps, a six-month multidisciplinary pilot inpatient palliative care consultation service was developed, aiming to improve symptom control, provide psychosocial support, facilitate goals-of-care discussions, and reduce potentially avoidable intensive care unit admissions. Conclusions: This real-world longitudinal experience demonstrates substantial palliative care needs among oncology patients in a resource-limited setting. The observed patient characteristics underscore the urgency of structured palliative care integration. Implementation of a pilot inpatient palliative care consultation service represents a feasible and scalable quality-of-care intervention, with the potential to improve patient outcomes, optimize resource utilization, and support sustainable integration of palliative care into routine oncology practice.

Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Final analysis results from the phase 3 KEYNOTE-522 study.

507 Background: KEYNOTE-522 (NCT03036488) showed statistically significant and clinically meaningful improvements in pCR, EFS, and OS with the addition of pembrolizumab (pembro) to chemotherapy (chemo) in participants (pts) with high-risk early-stage TNBC. Here, we present updated results from the final analysis. Methods: Eligible pts with previously untreated, non-metastatic, centrally confirmed TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or placebo (pbo), both given with 4 cycles of paclitaxel + carboplatin, then 4 cycles of doxorubicin or epirubicin + cyclophosphamide. After definitive surgery, pts received adjuvant pembro or pbo for 9 cycles or until recurrence or unacceptable toxicity. Dual primary endpoints are pCR (ypT0/Tis ypN0) and EFS (time from randomization to disease progression that precluded definitive surgery, local/distant recurrence, second primary cancer, or death from any cause); OS is the key secondary endpoint. Results: 1174 pts were randomized to pembro (n = 784) or pbo (n = 390). At the data cutoff date (October 14, 2025), median follow-up (range) was 93.8 mo (84.7-102.8). The 7-yr EFS rate (95% CI) was 78.3% (75.3-81.1) in the pembro group vs 69.8% (65.0-74.2) in the pbo group; the HR was 0.68 (95% CI, 0.54-0.86). The 7-yr OS rate (95% CI) was 85.1% (82.5-87.5) in the pembro group vs 77.2% (72.7-81.1) in the pbo group; the HR was 0.64 (95% CI, 0.49-0.85). The benefit of pembro on EFS and OS was generally consistent across most prespecified subgroups, including those defined by PD-L1 expression, nodal status, and disease stage. Rates of grade ≥3 treatment-related AEs were 77.1% in the pembro group and 73.3% in the pbo group (death incidence, 0.5% vs 0.3%, respectively); rates of any grade immune-mediated AEs were 35.0% vs 13.1%, respectively. Conclusions: After a median follow-up of 7.8 years, neoadjuvant pembro + chemo followed by adjuvant pembro continues to show a clinically meaningful survival benefit compared with neoadjuvant chemo alone in pts with high-risk early-stage TNBC. Clinical trial information: NCT03036488 .

Immunotherapy-based total neoadjuvant therapy versus neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cancer: Interim results of a randomized phase 2 study.

e16110 Background: Long-term outcomes of neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal squamous cancer (LA-ESCC) are unsatisfactory. The short-term efficacy of concurrent nCRT and immunotherapy isn’t superior to that of nCRT. The use of total neoadjuvant therapy (TNT), which includes sequential chemotherapy and chemoradiation, is increasing in other malignancies and promises enhanced systemic disease control. The purpose of this study is to assess the efficacy and safety of the integration of tislelizumab, a PD-1 inhibitor with TNT (iTNT) in LA-ESCC. Here, we report our interim results. Methods: This is a prospective, single center, randomized, phase 2 trial. Eligible patients with thoracic LA-ESCC (cT1b-3N1-3M0 or cT3N0M0) were randomized in a 1:1:1 ratio into each of the three treatment arms and then surgery. All patients received nCRT (40Gy/20f with concurrent nab-paclitaxel and cisplatin). Arm A: nCRT followed by consolidation immunochemotherapy (ICT); Arm B: induction ICT followed by nCRT; Arm C: nCRT alone. The ICT regimen consisted of two 3-week cycles of tislelizumab plus nab-paclitaxel and cisplatin. The primary endpoint is the pathological complete response (pCR) rate, the secondary endpoints are R0 resection rate, 1-year and 2-year disease-free survival and overall survival and safety. Results: From February 2025 to December 2025, 90 patients were enrolled. At the time of writing, 65 patients (Arm A n = 19, Arm B n = 21, Arm C n = 25) completed neoadjuvant therapy and accepted surgery in per protocol set (PPS). One patient was inoperatable because of disease progression (Arm A), 9 patients are awaiting surgery; 15 patients remain on neoadjuvant treatment. Among the 65 patients who have received surgery, the incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 36.8% (7/19) for Arm A, 42.9% (9/21) for Arm B and 20.0% (5/25) for Arm C. No grade 5 TRAEs were reported. In Arm A, Arm B and Arm C groups, the rates of surgical complications of any grade were 63.2% (12/19), 47.6% (10/21) and 44.0% (11/25), respectively. Among these, the proportions of Clavien-Dindo grade 3-4 complications were 21.1% (4/19), 14.3% (3/21) and 8.0% (2/25), respectively. There was no postoperative 30-day mortality. All 65 patients achieved R0 resection. The pCR rate was 63.2% (12/19) in arm A, 76.2% (16/21) in arm B and 24.0% (6/25) in arm C (Table 1). The pCR rate was 70.0% (28/40) in the iTNT group (arm A + arm B). Conclusions: Immunotherapy-based TNT has achieved an encouraging pCR rate and a tolerable safety profile. Clinical trial information: ChiCTR2500098409. Pathological outcomes. Arm A (n=19) Arm B (n=21) Arm C (n=25) pCR 63.2% 76.2% 24.0% ypT0 63.2% 76.2% 40.0% ypN0/N1/N2-3 84.2% / 10.5% / 5.3% 90.5% / 0.0% / 9.5% 56.0% / 24.0% / 20.0%

Evolving trends in young adult (YA) gastrointestinal (GI) cancer: Philadelphia in national context.

e15706 Background: GI malignancies in YA (ages 18-39) have increased in the past several decades, with advanced stages at diagnosis and aggressive tumor features relative to patients (pts) with average age onset disease. In Pennsylvania, age-adjusted incidence reached as high as 119.6 per 100,000 in 2015 among individuals under 50—exceeding the national average of 102.97. We evaluated differences in disease burden of YA GI cancers at Temple University Hospital System (TUHS), Philadelphia’s primary safety net hospital, compared with national data. Methods: A retrospective analysis of pts aged 18-44 with GI malignancies at TUHS (2010-2024) relative to data available at the National Cancer Database (NCDB). Group differences were assessed with Chi-square or Fisher’s exact tests for categorical variables and t-tests or Mann–Whitney U tests for continuous variables, with temporal trends in GI cancer subtypes evaluated using yearly plots. Results: 530 pts at TUHS and 81,097 in the NCDB were included. The average age at diagnosis was higher at TUHS (37.6 vs 32.9 years), with a greater portion of black pts (22.1% vs 15.5%). TUHS pts presented with more advanced stages at diagnosis and were more likely to rely on government insurance (30.3 vs 27.5%). Compared with the NCDB, TUHS pts were diagnosed with more stage III (27.4% vs 12.6%) and stage IV disease (33.8% vs 22.1%), however a portion of pts in the NCDB did not have stage reported. Time from diagnosis to treatment was longer at TUHS, with black pts nearly 9 days longer than the overall national average (31.72 vs 22.8 days). Black pts had higher rates of pancreas (8.6 vs 7.6%), small intestine (5.6 vs 4.3%) and anal (8.7 vs 3%) cancers compared to white pts in both TUHS and NCDB, with starker contrast in the TUHS population (13.7 vs 7.2%, 8.5 vs 6.2%, 5.1 vs 1.2% ). Rectal cancer was lower in black pts relative to white (13.3 vs 17.2%) in both cohorts. At TUHS, black pts had a higher rate of colon/rectosigmoid (42.8 vs 41.7%), esophageal (3.4 vs 3.1%) and intrabiliary (2.6 vs 2.5%) cancers relative to white pts, which was converse to the NCDB. Asian/Pacific Islander pts had a higher percentage of stomach and liver cancer across all races, with the largest difference seen relative to white pts (14.7 vs 8.4%, 8.4 vs 2.9% respectively). Conclusions: GI malignancies in YA treated at TUHS had similar disease burden compared to national counterparts, but was characterized by advanced stages at diagnosis, longer time to treatment, and greater racial disparities in tumor distribution. These findings suggest that structural and sociodemographic factors, including insurance status and race, may contribute to delayed diagnosis and inequities in care. Targeted interventions aimed at improving early detection, expediting treatment initiation, and addressing race-specific and site-specific cancer disparities are urgently needed to mitigate the growing burden of YA GI cancers in underserved populations.

Understanding the understanding: Patient assessment of goals and treatment in oncology.

e24066 Background: Metastatic disease is typically treated with the goal to prolong life, but not cure the disease, or what’s called palliative intent. However, patients do not always understand the goals of their cancer treatment, which can lead to confusion, mistrust, grief, etc. Our institution did a survey to evaluate our patients understanding of their treatment goals back in 2020. At that time, only about 23% of the patients studied with stage IV disease knew their treatment intent was not curative. Due to this, our facility has striven to spend more time with patients discussing their goals, offering support groups and educational resources, and involving palliative care earlier in their treatment course when indicated. This study was done as a follow up to this previous study to evaluate if meaningful change has been accomplished. Methods: This was a prospective study of 97 patients at a single institution with a variety of solid tumors. During a patient’s routine visit with their oncologist, they were given a survey. This survey included questions about what type of cancer they had, how long they’ve been on treatment, if they think their treatment is curative, whether they think their treatment will help them live longer, if they know the meaning of the word palliative, quality of life, if any resources were given to them, and if they’ve seen anyone from palliative care before. Patients also gave basic demographic information. Their answers were compared using Pearson’s chi-square test and Fisher’s exact test. Results: Primary malignancies consisted of gastrointestinal, head and neck, breast, lung, prostate, and sarcoma. 62% of the patients were female. The median age was around 57. 45% of patients knew that their treatment was not curative. 34% of the patients were unsure, and 21% thought their treatment was curative when it wasn’t. 89% of the patients thought their treatment would help them live longer, and 51% reported they were happy with their quality of life. 68% of patients didn’t know what the word palliative meant. 34% of the patients had seen palliative care before, and of the patients who hadn’t, 39% of them were interested in seeing palliative care. Demographics did not play a significant role on how patients perceived their disease. Conclusions: In comparison to our previous study, patient's understanding of their disease being incurable has improved from about 23% to 45%. Continued education and ongoing studies will be needed to evaluate what is most helpful in informing and empowering our patients about their disease.

A study of MT-4561 in patients with various advanced solid tumors (NCT06943521).

TPS3178 Background: MT-4561 is a bromodomain-containing protein 4 (BRD4) protein degrader, which is a bi-functional molecule having both a binder moiety that binds to BRD4 and a degron moiety that binds to damage-specific deoxyribonucleic acid (DNA) binding protein 1 (DDB1) and cullin 4 (CUL4) associated factor 16 (DCAF16), which is responsible for the ubiquitination of BRD4. MT-4561 degrades BRD4, a bromodomain protein that stimulates oncogene transcription, using the ubiquitin-proteasome system. Tanabe Pharma has demonstrated that this novel BRD4 degrader, MT-4561, exerts continuous anti-tumor effects in various cancer xenograft models (Ooike, 2024). Methods: This trial is a FIH, Phase I/II study to evaluate safety, tolerability, PK, PD, and efficacy of MT-4561 in patients with advanced solid tumors. Part 1 is evaluating safety, tolerability, PK, MTD, and the doses to be investigated in Part 2 (dose optimization) using the BOIN design. Part 2 evaluates the safety and efficacy of MT-4561 in patients with pre-specified tumor types based on data from Part 1, and to determine the RP2D. Part 2 can begin enrollment after the MTD and/or the doses to be investigated in Part 2 have been determined based on data from Part 1. Part 3 of the study is the open-label drug-drug interaction (DDI) cohort to evaluate the effect of MT-4561 on the PK established in Part 1. A retrospective analysis will also be conducted to assess the correlation between efficacy and expression of BRD4/its downstream gene products in patient samples to explore predictive biomarkers. MT-4561 is administered as an intravenous (IV) infusion over 30 minutes once every week in 28-day cycles, until disease progression or discontinuation criteria are met. Parts 1 and 3 of the study will enroll patients 18 years and older with who have failed at least 1 therapy , who have ≥ 1 measurable lesion by RECIST v1.1 and with confirmed histologic or cytologic diagnosis of one of the following tumors: HNSCC, NSCLC, esophageal cancer, gastric cancer, biliary tract cancer, PDAC, breast cancer, ovarian cancer, cervical cancer, endometrial cancer, prostate cancer, urothelial carcinoma, NET or NEC, soft tissue sarcoma, and NUT carcinoma. Part 2 will enroll only pre-specified tumors for dose optimization to determine the RP2D. Key exclusion criteria include patients with unresolved ≥ Grade 2 toxicities from previous treatment and those with QTc prolongation > 470 msec at screening. Also, patients who received drugs with a known risk of QT interval prolongation or torsade de pointes, before the start of IMP administration. Enrollment in Part 1 of the study began May 2025 and continues to enroll patients in the US and Japan with 10 patients enrolled through Dose Level 2 as of Jan 2026. The safety data along with DLT continues to be reviewed in Part 1. Ooike S, et al. PB069, Poster Session, 36th EORTC-NCI-AACR Symposium, 2024. Clinical trial information: NCT06943521 .

Socioeconomic and treatment-related determinants of long-term cancer survival: A population-based SEER outcomes analysis.

11186 Background: Cancer survival is shaped by tumor biology, treatment access, and socioeconomic context, yet population-level quantification of long-term survival disparities related to chemotherapy use and income is limited. We assessed five-year cancer-specific survival across demographic, treatment, and socioeconomic strata in a national registry. Methods: We performed a retrospective, population-based survival analysis using the Surveillance, Epidemiology, and End Results (SEER) database. Cancer-specific survival was evaluated at 12, 24, 36, 48, and 60 months after diagnosis. Outcomes were stratified by sex, race, chemotherapy receipt, and area-level median household income categories. Survival estimates were summarized descriptively and visualized using time-to-event curves. Results: Overall cancer-specific survival declined progressively over five years, from ~84% at 12 months to ~58% at 60 months. Sex differences were minimal, with similar five-year survival among males and females (~57–58%). Racial disparities were substantial: Asian/Pacific Islander patients demonstrated the highest survival across follow-up, while Black and American Indian/Alaska Native patients had lower early survival and persistent gaps at five years. Patients with recorded chemotherapy use had improved survival compared with those without or with unknown chemotherapy status; 12-month survival was ~88% versus ~80%, and five-year survival was ~65% versus ~57%, respectively. A pronounced socioeconomic gradient was observed: individuals in areas with median household income ≥$120,000 had higher five-year survival (~67%), whereas those in areas with income < $40,000 had markedly lower survival (~52%). Conclusions: In this national registry analysis, both chemotherapy utilization and higher socioeconomic status were strongly associated with improved long-term cancer survival, whereas persistent racial and income-related disparities remained evident. These findings highlight ongoing inequities in access to oncologic care and support the need for targeted policy interventions and equity-focused treatment delivery models. Interpretation should account for limitations inherent to observational registry data and potential residual confounding.

Impact of the Taylor Cancer Research Center (TCRC) and Tempus AI TIME Partnership on clinical trial start-up and accrual.

1565 Background: TCRC is a nonprofit oncology community practice serving patients in Northwestern Ohio. TCRC's partnership with the Tempus AI TIME program leverages proprietary software and nursing teams to support patient matching across a portfolio of industry-sponsored clinical trials. Trials may be rapidly opened "prospectively" before an eligible patient is identified, or "just-in-time" (JIT) once a patient is identified and ready to consent, allowing studies to be activated in response to patient need. The goal of this partnership is to utilize AI-enabled technology and clinical workforce support to alleviate site burden associated with activating and enrolling patients to oncology clinical trials, thereby increasing patient access to novel therapies and optimizing resource utilization. Methods: Tempus’ AI-enabled platform analyzes trial eligibility criteria and compares this against patient-level information from a combination of structured EMR data, natural language processing, and large language models. All patients are evaluated against the full TIME trial portfolio nightly, with potential matches reviewed by Tempus nurses. Patients likely to be eligible for a trial are communicated to TCRC for final confirmation. Trials are rapidly activated through a standardized operational model including a pre-negotiated clinical trial agreement, rate card, and central IRB. Program metrics include number of patients pre-screened, trial activation timelines, and trial consents. Results: From June 2024 to August 2025, Tempus nurses spent approximately 219 hours pre-screening 1,195 patients from TCRC, yielding 278 potential matches across 92 TIME trials. TCRC activated 16 TIME trials, leading to a total of 66 consents. Within the same time, TCRC activated 9 non-TIME trials resulting in 30 consents. TIME trials averaged 4.1 consents per trial, compared to 3.3 consents for non-TIME trials. TIME activations averaged 10.5 business days for JIT and 15.9 days for prospective trials, versus 55.4 days for non-TIME trials. Conclusions: TCRC's partnership with the Tempus AI TIME program, including enhanced patient pre-screening resources and rapid trial activation model, reduced trial start-up time with an increase in total consents and consents per trial compared with traditional trials. TCRC activated TIME trials 4x faster with a 2x increase in interventional consents and 120% increase in overall consents compared with non-TIME studies. This demonstrates how AI-enabled trial matching, combined with a streamlined operational model, can improve resource utilization and patient access to precision oncology trials in a community setting. Average activation time (days) Interventional trials Consents per trial (interventional) Observational trials Consents per trial (observational) Total consents Consents Per Trial TIME 13.7 12 2.3 4 9.8 66 4.1 Non-TIME 55.4 6 1.1 3 7.6 30 3.3

Standardized exam-style benchmarking of large language models in breast cancer clinical decision-making.

553 Background: Large language models (LLMs) are increasingly used to support clinical reasoning in breast cancer (BC), yet reproducible benchmarking remains limited. In our prior work using complex breast cancer clinical scenarios (BCCS), OpenEvidence (OE) outperformed other LLMs; however, expert Likert-based grading may be influenced by subjective interpretation and human bias. Standardized, board-style multiple-choice questions—required even for expert clinicians—offer an objective framework to assess LLM accuracy and inform readiness for potential clinical decision support. We evaluated the accuracy of four LLMs on a standardized BC question set using binary grading and paired statistical testing. Methods: One hundred BC questions reflecting real-world clinical scenarios were submitted to four LLMs: ChatGPT-5.2 (GPT), Google Gemini 3 (Gemini), Claude Sonnet 4.5 (Claude), and OE. Questions were sourced from a hematology–oncology question bank and spanned major BC subtypes and treatment settings. Model responses were graded against bank-designated correct answers using binary scoring (1=correct, 0=incorrect). Overall accuracy with 95% confidence intervals (CI) was calculated. Pairwise comparisons were performed using McNemar’s test. Results: One hundred clinical scenarios were evaluated spanning all major BC subtypes and treatment settings, including early-stage and metastatic disease, and neoadjuvant and adjuvant therapy. Overall accuracy was highest for Gemini at 94.0% (95% CI, 87.4–97.8), followed by GPT at 90.0% (95% CI, 82.4–95.1), OE at 90.0% (95% CI, 82.4–95.1), and Claude at 89.0% (95% CI, 81.2–94.4). McNemar’s test showed no statistically significant differences between models. Compared with Gemini, GPT showed 4% lower accuracy (p=0.289), Claude 5% lower (p=0.267), and OE 4% lower (p=0.289). GPT and OE demonstrated equivalent accuracy (both 90.0%) with no significant difference (p=1.000). GPT vs Claude differed by 1% (p=1.000) and Claude vs OE differed by 1% (p=1.000). All models generated clinical reasoning, while OE was the only model providing citations. Conclusions: In standardized BC clinical scenarios, four widely used LLMs demonstrated high accuracy with no significant between-model differences. However, no model achieved 100% accuracy, reinforcing the need for ongoing refinement and clinician oversight prior to clinical use. Future studies should expand question volume, evaluate domain-specific error patterns, and incorporate question banks from multiple countries and geographic regions to improve generalizability before real-world clinical deployment.

Factors associated with time to breast cancer treatment initiation at an urban safety net center.

e13750 Background: Delays in cancer treatment initiation are associated with increased mortality and may disproportionately affect socioeconomically disadvantaged patients. We evaluated sociodemographic and clinicopathological factors associated with time to initial treatment (TT) − defined as days to first surgery, chemotherapy, or radiation − in patients with primary breast cancer at an urban safety net center in 2022. Methods: We conducted a retrospective analysis of 70 patients treated at our institution. Variables included age, race, insurance status, AJCC clinical stage, Ki-67 % scores, hormone receptor status, HER2 status, aerial distance to center, and Area Deprivation Index (ADI). TT was measured in days and was normally distributed. Untransformed values were used in analyses. Univariable analysis was followed by a multivariable regression analysis to identify factors associated with ± TT (- indicating shorter TT, + indicating longer TT). Results: 70 patients were included. Mean (SE) TT was 79.0 (4.4) days, mean distance to care was 9.0 (0.8), mean ADI was 74.0 (2.5), and mean Ki-67 was 41.2% (3.9). AJCC Clinical Stage distribution was: 57.1% (n = 40) stage I, 21.4% (n = 15) stage II, 10% (n = 7) stage III, and 2.9% (n = 2) stage IV. The cohort was 40.0% Black (n = 28), 37.1% White (n = 26), 12.9% Latino (n = 9), 7.1% Asian/Pacific Islander (n = 5), and 2.9% Native American (n = 2). Insurance status was Medicaid in 35.7% (n = 25), Medicare in 20.0% (n = 14), private in 30.0% (n = 21), and self-pay in 14.3% (n = 10). Hormone receptor–positive disease was present in 75.7% (n = 53) and HER2-positive disease in 22.9% (n = 16). Variables significant on univariable analysis and included in the multivariable model were distance, ADI, Ki-67, race, insurance status, AJCC stage, hormone receptor status, and HER2 status. The model was statistically significant (F = 2.23, p = 0.014) and explained 46.5% of the variance in TT (R² = 0.47, adjusted R² = 0.26). Compared with privately insured patients, Medicaid was associated with +41.1 days TT (p = 0.001, 95% CI 18.5, 63.7), and self-pay with +34.8 days TT (p = 0.039, 95% CI 1.8, 67.8). Medicare was associated with +27.0 days TT (p = 0.066, 95% CI −1.8, 55.8). AJCC stage IV disease was associated with −85.9 days TT (p = 0.023, 95% CI −159.5, −12.3). Hormone receptor positivity showed a trend towards increased TT at +25.1 days (p = 0.053, 95% CI −0.4, 50.6). Distance to care, ADI, race, HER2 status, and Ki-67 were not independently associated with TT (all p > 0.05). Conclusions: Self-pay and Medicaid status were associated with treatment delay, highlighting an underlying disparity in breast cancer care. Advanced-stage disease was associated with faster treatment initiation, consistent with appropriate clinical triage. A trend towards treatment delay for hormone-positive disease may highlight a need to balance prioritization of advanced breast cancer with ensuring timely management or referral for all cases.

Does neoadjuvant chemotherapy matter in endocrine-sensitive breast cancer?: Insights from a 10-year SEER cohort.

e12626 Background: In ER+/HER2– breast cancer, neoadjuvant chemotherapy (NAC) is used far less frequently than in other biologic subtypes, largely because endocrine-sensitive tumors usually have favorable biology and show excellent long-term outcomes with surgery and endocrine therapy alone. NAC is sometimes pursued for downstaging, especially in large T3 tumors or when breast conservation is desired. However, whether NAC provides a meaningful overall survival (OS) benefit in T2–T3, N0–1 ER+/HER2– disease remains uncertain. This study evaluates the association between NAC and OS using contemporary, population-level data. Methods: We conducted a retrospective cohort analysis using SEER Research Plus 17 registries (2000–2022; Nov 2024). We included patients with T2 or T3, N0–1, M0, ER+/HER2– breast cancer diagnosed between 2013-2022. Patients were grouped by receipt of NAC versus no NAC. Five-year OS was estimated using Kaplan–Meier methodology and compared with log-rank testing. Analyses were stratified by T2 and T3 tumor status. Results: A total of 5,792 patients met criteria. In the T2 subgroup, 1,631 patients received NAC and 3,761 did not. Five-year OS was 84.3% with NAC versus 87.1% without NAC, a statistically significant difference favoring omission of NAC (Z = 3.944; p = 0.00004). In the T3 subgroup (398 NAC vs 514 no NAC), five-year OS was 74.5% for those receiving NAC compared with 84.3% among patients not treated with NAC (Z = 1.743; p = 0.04). Across both tumor sizes, NAC did not confer a survival advantage; instead, OS consistently favored patients treated without NAC, including those with larger tumors where downstaging considerations often influence treatment decisions. Conclusions: In this population-based analysis, neoadjuvant chemotherapy did not improve overall survival in ER+/HER2– T2–T3, N0–1 breast cancer and was associated with worse outcomes compared with no NAC. These findings highlight the limited value of NAC in endocrine-sensitive disease and support a selective, biology-driven approach rather than relying on tumor size alone. Interpretation is limited by SEER’s lack of data on progression-free survival, locoregional recurrence, treatment intent, genomic assays, and endocrine therapy adherence. Prospective studies are needed to determine whether any subgroup of these patients derives meaningful benefit from NAC.

Real-world use of piflufolastat F 18 and imaging-associated treatment patterns in early-stage prostate cancer.

e17126 Background: Positron emission tomography (PET) imaging with piflufolastat F 18, a PSMA-targeted radiotracer for prostate cancer (PCa), has shown value in clinical trials, but real-world use remain underexplored. The objective of this retrospective observational study was to examine the utilization of piflufolastat F 18 among patients with low- to intermediate-risk PCa and evaluate subsequent treatment patterns. Methods: Patients with PCa from community urology practices were identified from the PPS Analytics electronic health record database and restricted to those having ≥1 imaging scan between June 2021–August 2024, a Gleason score of 6 or 3+4 within 6 months of imaging, and no biochemical recurrence. Patients were grouped into two cohorts: (1) those imaged with piflufolastat F 18, and (2) those who only received conventional imaging. Time-to-event outcomes were assessed using Kaplan-Meier analysis. Results: A total of 1,274 patients were included in the piflufolastat F 18 cohort and 25,869 in the conventional imaging cohort. Mean (SD) age was 71.5 (8.4) in the piflufolastat F 18 cohort, and 67.9 (8.1) in the conventional imaging cohort. Gleason score 6 was observed in 53.7% of the piflufolastat F 18 cohort and 59.4% of the conventional imaging cohort, and Gleason score 7 (3 + 4) was observed in 46.3% and 40.6%, respectively. Those imaged with piflufolastat F 18 were more likely to receive treatment during follow-up (74.7% vs. 44.7%) and less likely to undergo active surveillance (5.7% vs. 26.7%). They more frequently received androgen deprivation or hormonal therapy (69.6% vs. 37.3%) and novel hormonal therapy (14.7% vs. 0.3%). In contrast, conventional imaging patients more often underwent prostatectomy (45.3% vs. 23.2%) or radiation therapy (42.0% vs. 35.8%). The piflufolastat F 18 cohort also had fewer follow-up imaging scans (20.7% vs. 39.5%) and a longer median time to next imaging (28.1 vs. 26.3 months). Conclusions: In this cohort of early-stage patients with PCa, imaging with piflufolastat F 18 demonstrated different treatment patterns and follow-up imaging rates compared to conventional imaging. These results suggest that piflufolastat F 18’s may impact clinical decision-making and resource use. Future studies should examine longer-term outcomes following initial piflufolastat F 18 imaging. Treatment patterns and time to next imaging after piflufolastat F 18 vs conventional imaging in low- to intermediate-risk prostate cancer. Piflufolastat F 18 (N = 1,274) Conventional Imaging (N = 25,869) Treatment, n (%) 952 (74.7) 11,563 (44.7) ADT or hormonal therapy 663 (69.6) 4,311 (37.3) Novel hormonal therapy 140 (14.7) 38 (0.3) Prostatectomy 221 (23.2) 5,234 (45.3) Radiation 341 (35.8) 4,852 (42.0) Active Surveillance, n (%) 73 (5.7) 6,917 (26.7) Time to next imaging Events, n (%) 264 (20.7) 10,212 (39.5) Median (months), [95% CI] 28.1 [24.6, NR] 26.3 [25.4, 27.4]

Expression of Concern: Genetic Diversity and Demographic History of Cajanus spp. Illustrated from Genome-Wide SNPs

Vacuum barrier engineering tunneling magnetoresistance in van der Waals Fe5GeTe2 homojunctions

The atomically thin and flexible characteristics of 2D van der Waals (vdW) materials allow for high-quality, tunable multilayer stacking. This gives rise to pure physical phenomena and broad application prospects in spintronics. Recently, very high tunneling magnetoresistance (TMR) has been obtained in all-vdW magnetic tunnel junctions (MTJs), indicating the potential of vdW materials for non-volatile spintronic memory applications. Here, we report an all-vdW MTJ device based on an Fe5GeTe2 homojunction, using a vacuum layer as the tunneling barrier. The TMR value first increases and then decreases as the thickness of the vacuum barrier layer grows, with a maximum TMR value reaching up to 68.4%. We also propose an in-plane electron momentum (k∥) resolved tunneling model specifically for TMR calculation in ferromagnetic homojunctions, which can well explain our experimental results. The simplified bilayer-MTJ structure offers attractive possibilities for spin-based memory, logic, and neuromorphic computing.

Optimizing a novel green synthesis of zincite nanoparticles using knotwood biomass residue of Eucalyptus citriodora: A multi-technique characterization and antifungal analysis

Conformationally Variable Peptides Trap and Detoxify Ox‐LDL in Plaques for Attenuating Atherosclerosis in Multiple Species

ABSTRACT Cardiovascular and cerebrovascular events due to atherosclerosis (AS) are the leading causes of mortality worldwide. Current therapeutic strategies failed to simultaneously target lipid deposition, chronic inflammation, and endothelial dysfunction. Herein, we developed BIFD, a conformationally variable peptide targeting lysophosphatidylcholine (LPC) on oxidized low‐density lipoproteins (ox‐LDL), which binds ox‐LDL to form nanoaggregates, blocking ox‐LDL toxicity, reducing inflammation, promoting metabolism/excretion of ox‐LDL in macrophage. In addition, both ox‐LDL specifically distributed in plaque sites and the targetability of BIFD to ox‐LDL enable the BIFD targetability to plaque of AS. Therefore, rapamycin (Rapa), an anti‐inflammatory drug, is designed to be encapsulated into BIFD to form Rapa@BIFD nanoparticles (NPs). Rapa@BIFD may target plaque, enhancing accumulation and retention of Rapa@BIFD on the AS lesion. Consequently, Rapa@BIFD demonstrated high efficacy against AS with minimal side effects. In vitro and in vivo studies in apolipoprotein E‐knockout murine and canine models revealed that Rapa@BIFD effectively reduced oxidative damage, and inflammatory responses, while promoting lipid metabolism and excretion. Rapa@BIFD mitigated side effects of Rapa, such as hyperlipidemia and splenic toxicity. These findings present a transformative multitarget for AS, combining efficacy with minimal side effects and enhanced clinical translatability.