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Using artificial intelligence (AI) as a decision support tool in clinic.
e13647 Background: Multidisciplinary reviews (MDR) can alter the management of cancer cases. We previously presented more than 400 real-world cases across 5 cancer types to an expert MDR panel comprising radiology, medical, surgical, radiation, and hematologic oncology. Here, we evaluate the alignment and competence of recommendations generated by 3 leading AI models relative to those made by an MDR panel. Methods: We reviewed 261 complex cases in breast, lung, heme, gastrointestinal (GI), and genitourinary (GU) cancers previously adjudicated by an MDR panel between 2020 and 2021 from a larger cancer database. Cases were analyzed by AI models (OpenAI’s ChatGPT 4.5, Anthropic’s Claude Opus 4 and Google’s Gemini Ultra) using PrecisCa’s proprietary prompting method. Individual AI-generated recommendations from each model were scored on a scale of 1-5 (5 highest) across 6 domains: completeness, reasoning, clarity, menu of options, recency, and relevance versus the MDR panel recommendations. The maximum achievable score was 30 per case, yielding a total achievable aggregate score of 7,830. Final AI recommendations were also compared to National Comprehensive Cancer Network (NCCN) guidelines for discrepancies. Reverse comparisons of additional AI-recommended options not identified by the MDR panel were not performed due to interval updates in the past 5 years. Results: Across the board (Table 1), AI systems excelled in recency but not in completeness. While variability existed among the 3 AI models, alignment with MDR expert recommendations was high. Discordant cases reflected minor differences in option selection and were unlikely to have resulted in clinically meaningful changes in management. Conclusions: This study demonstrates a high degree of alignment between recommendations generated by 3 leading AI models and those of a MDR panel across multiple complex cancer cases. These findings support the potential role of AI as a clinical decision support tool when used in conjunction with human experts’ review, rather than as a replacement for multidisciplinary care. Characteristics and aggregate/median competence score (range) by cancer type. Cancer Type n Histology (%) ChatGPT 4.5 Claude Opus 4 Gemini Ultra Breast 70 Ductal 90; Lobular 10 1868/25.5 (21-30) 1940/23.5 (17-30) 1965/25.5 (21-30) Lung 70 Non-small cell 92.9; Small cell 7.1 1860/25 (20-30) 1942/25 (20-30) 1971/26 (22-30) Heme 38 Hodgkin lymphoma 13.2; Leukemia 10.5; Multiple myeloma 36.8; Non-Hodgkin lymphoma 39.5 849/22.5 (15-30) 932/22.5 (15-30) 964/22.5 (15-30) GI 48 Anal 6.25; Colorectal 43.8; Esophageal 12.5; Gastric 6.25; Hepatobiliary 10.4; Pancreatic 20.8 1231/20.5 (11-30) 1249/20.5 (11-30) 1264/21.5 (13-30) GU 35 Bladder 20; Kidney 31.4; Prostate 42.9; Testicular 5.7 880/23.5 (17-30) 931/23.5 (17-30) 889/24 (18-30) Total 261 6688/20.5 (11-30) 6994/20.5 (11-30) 7053/21.5 (13-30)
Tolerance of gemcitabine–oxaliplatin (GEMOX) in advanced and metastatic gallbladder cancer: A real-world, single-center retrospective study from north India.
e16224 Background: Gallbladder cancer (GBC) is highly prevalent in North India and commonly presents at an advanced or metastatic stage. GEMOX is frequently used as first-line chemotherapy; however, real-world data on treatment tolerance in this high-burden setting are limited. This retrospective study evaluated the toxicity profile and treatment feasibility of GEMOX in patients with advanced and metastatic GBC treated in routine clinical practice. Methods: This retrospective, single-center study included adults with unresectable or metastatic gallbladder adenocarcinoma treated with GEMOX between January 2020 and June 2025, either in the first line or in later lines. GEMOX was administered every 14 days (gemcitabine 1000 mg/m², oxaliplatin 100 mg/m²). Treatment tolerance was the primary endpoint and was assessed by the incidence and severity of adverse events graded per CTCAE v5.0, as well as dose reductions and treatment discontinuation due to toxicity. Data were extracted from institutional electronic health records and analyzed descriptively. Results: Of 379 patients with gallbladder cancer screened, 219 received GEMOX in the first or second line; 38 were excluded due to incomplete data, leaving 181 patients for analysis. Median age was 52 years, 71.3% were female, and ECOG performance status was 0–1 in 52.5%, 2 in 42.0%. At presentation, abdominal pain and jaundice were noted in 87.3% and 43.7% of patients, respectively, and 26.5% required biliary drainage (PTBD 17.1%, biliary stenting 9.3%). Most patients had metastatic disease (90.1%), with the liver as the most common metastatic site (69%). Median baseline CA 19-9 was 150 U/mL (range, 0.19–46,600). The median number of chemotherapy cycles delivered was 5 (range, 1–19). Anemia and peripheral sensory neuropathy (PSN) were the most common toxicities (any grade: 89.5% and 64.6%), with grade ≥3 events in 35.4%, mainly PSN (16.0%) and anemia (15.5%) (Table 1). Dose reductions occurred in 28.7% and treatment discontinuation due to toxicity in 17.1%, most often from cumulative neuropathy. Median progression-free survival was 4.2 months (95% CI, 3.85–4.55). Conclusions: Gemcitabine–oxaliplatin showed a manageable real-world toxicity profile in advanced gallbladder cancer, with treatment-limiting effects driven mainly by cumulative neuropathy and anemia. These data support the feasibility of GEMOX in routine practice in a high-burden setting. Treatment-related toxicities and tolerance with gemox (n = 181). Toxicity / Tolerance Parameter n (%) Any-grade anemia 162 (89.5) Any-grade PSN 117 (64.6) Any-grade nausea/vomiting 134 (74.0) Grade ≥3 toxicity (overall) 64 (35.4) Grade 3 PSN 29 (16.0) Grade 3 anemia 28 (15.5) Grade 3 nausea/vomiting 13 (7.2) Dose reductions required 52 (28.7) Treatment discontinuation due to toxicity 31 (17.1)
Clinical impact of baseline serotonergic antidepressant use on survival and immune-related adverse events in lung cancer patients treated with immune checkpoint inhibitors: A large multicenter matched cohort study.
e20618 Background: Preclinical and mechanistic studies suggest that serotonergic antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), may exert antitumor and immunomodulatory effects through modulation of serotonin signaling, T-cell function, cytokine production, and the tumor microenvironment. However, whether these proposed effects translate into clinically meaningful outcomes or altered toxicity profiles in patients treated with immune checkpoint inhibitors (ICIs) remains uncertain. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, including adult lung cancer patients treated with ICIs between January 2015 and January 2026. Baseline SSRI/SNRI exposure was defined as use within 3 months prior to ICI initiation. Among 78,852 eligible patients (12,508 exposed; 66,344 unexposed), 1:1 propensity score matching yielded 22,940 matched patients (11,470 per group). Matching variables included age, sex, comorbidities (COPD, chronic kidney disease, diabetes, liver disease), metastatic disease, brain metastases, and prior chemotherapy. The primary endpoint was overall survival over 5 years. Secondary endpoints included pneumonitis and endocrine immune-related adverse events evaluated within 90 days. Survival analyses used Kaplan–Meier methods and Cox proportional hazards models. Results: After propensity score matching, baseline demographic and clinical characteristics were well balanced between cohorts. Overall survival did not differ between patients receiving baseline SSRIs/SNRIs and those without serotonergic antidepressant exposure (median OS 671 vs 665 days; HR 1.01, 95% CI 0.97–1.04; p = 0.75). Rates of immune-related adverse events were comparable between groups, with no statistically significant differences in pneumonitis (HR 1.24, 95% CI 0.90–1.71; p = 0.29), hypothyroidism (HR 1.01, 95% CI 0.81–1.24; p = 0.24), or adrenal insufficiency (HR 1.21, 95% CI 0.87–1.66; p = 0.63). No clinically meaningful differences in immune-related toxicity risk were identified. Conclusions: In this large, propensity-matched real-world cohort of lung cancer patients treated with ICIs between 2015 and 2026, baseline SSRI/SNRI use was not associated with differences in 5-year overall survival or immune-related adverse event risk. Despite biologic plausibility and preclinical evidence suggesting potential antitumor or immunomodulatory effects of serotonergic antidepressants, these findings indicate that such effects may not translate into clinically significant survival benefit or altered immunotherapy toxicity in routine clinical practice. These results support the continued use of SSRIs/SNRIs when clinically indicated.
Atypical radiologic response patterns in patients treated on immunotherapy clinical trials: A retrospective lesion-level analysis.
e14600 Background: RECIST 1.1 is the standard method for tumor response assessment but may not adequately capture atypical radiologic response patterns observed with immunotherapy. We evaluated the frequency and prognostic significance of atypical responses using lesion-level longitudinal assessment in patients with advanced cancer treated with immunotherapy. Methods: We retrospectively analyzed patients with advanced solid tumors enrolled in seven phase I immunotherapy trials who underwent serial lesion-level radiologic assessment using an institutional tumor-tracking system interface. All target and non-target lesions were tracked across serial imaging studies. RECIST 1.1 responses were assessed. Atypical response patterns were defined as: mixed response (MR), concurrent ≥30% decrease in ≥1 lesion with ≥20% increase in ≥1 other lesion; oligoprogression (OP), progression in 1–3 lesions with stability or response in remaining lesions; pseudoprogression (PP), RECIST 1.1 progressive disease (PD) followed by subsequent stabilization or response; and hyperprogression (HP), ≥50% increase in tumor burden within 6–9 weeks of therapy. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression models. Results: Among 142 evaluable patients, 41 (28.9%) exhibited an atypical response: MR in 28 (19.7%), OP in 6 (4.2%), PP in 5 (3.5%), and HP in 2 (1.4%). At the time MR was identified, 64% of patients met RECIST PD; however, 44% continued treatment beyond PD and derived clinical benefit. Compared with patients achieving RECIST complete or partial response (non-MR), MR was associated with shorter PFS (HR 3.57; 95% CI, 1.45–9.09; p = 0.0056) and OS (HR 5.26; 95% CI, 1.41–20.00; p = 0.0134). In contrast, compared with RECIST PD patients (non-MR), MR was associated with longer PFS (HR 0.29; 95% CI, 0.16–0.53; p < 0.0001) and OS (HR 0.20; 95% CI, 0.10–0.41; p < 0.0001). PFS and OS did not differ between MR and RECIST stable disease (non-MR) (p = 0.19 and p = 0.29, respectively). Conclusions: Atypical radiologic response patterns occur in nearly one-third of patients treated with immunotherapy and are not adequately characterized by the limited surrogate lesions assessed by RECIST 1.1. MR represents a distinct intermediate prognostic group, while PP and HP are rare. Lesion-level longitudinal assessment may improve treatment decision-making in immunotherapy trials and become the basis for future disease response criteria. RECIST 1.1 Response characteristics in patients with mixed response. Category No. of Patients % RECIST 1.1 best response Partial response (PR) 7 25.0 Stable disease (SD) 16 57.1 Progressive disease (PD) 5 17.9 Objective response (all PRs) by metastatic site With liver metastases (n=19) 2 10.5 Without liver metastases (n=9) 5 55.6 With lymph node involvement (n=14) 6 42.9 Without lymph node involvement (n=10) 1 10.0
A phase 3, randomized, open-label study of INCB123667 versus investigator's choice of chemotherapy in patients with platinum-resistant ovarian cancer with cyclin E1 overexpression (MAESTRA 2, ENGOT-OV95, GOG-3137).
TPS5642 Background: Epithelial ovarian cancer (EOC) accounts for ~90% of ovarian cancers, with high-grade serous ovarian cancer (HGSOC) the most common histology. Despite high initial response rates to platinum-based therapy, ~70% of patients (pts) with advanced EOC relapse and nearly all recurrent disease ultimately becomes platinum resistant. Platinum-resistant ovarian cancer (PROC) remains a major therapeutic challenge with poor prognosis and limited treatment options. Standard therapies include single-agent, non-platinum chemotherapy with or without bevacizumab (bev), and mirvetuximab soravtansine (mirv) for pts with folate receptor alpha (FRα)-positive HGSOC. Approximately 50% of ovarian cancers overexpress cyclin E1. Cyclin E1 overexpression and increased cyclin-dependent kinase 2 (CDK2) activity are associated with poor outcomes and treatment resistance in ovarian cancer. A synthetic lethal relationship between CDK2 inhibition and cyclin E1 overexpression provides a strong biological rationale for selective CDK2 inhibition in this molecularly defined population. INCB123667 is a potent, selective, oral, small-molecule CDK2 inhibitor. In an ongoing phase 1 study, INCB123667 demonstrated manageable safety and objective response rates >30% in heavily pretreated pts with PROC and cyclin E1 overexpression [Damian S, et al. J Clin Oncol. 2025;43(16 suppl):5514; Simonelli M, et al. Ann Oncol. 2024;35(suppl 2):S495]. Methods: MAESTRA 2 (NCT07214779) is a global, multicenter, randomized, open-label phase 3 study evaluating the efficacy and safety of INCB123667 vs investigator’s choice chemotherapy (ICC) in ~466 female pts with platinum-resistant, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer with tumor cyclin E1 overexpression by immunohistochemistry (IHC; ≥75% of tumor cells with IHC score ≥1+). Eligible pts must have received 1-4 prior lines of systemic therapy, for whom single-agent chemotherapy is an appropriate next treatment. Pts should have received prior bev, and pts with FRα-positive disease should have received prior mirv. Pts are randomized 1:1 to INCB123667 50 mg twice daily or ICC (weekly paclitaxel, pegylated liposomal doxorubicin, gemcitabine, or topotecan). Randomization is stratified by primary platinum-free interval, ICC, and number of prior lines of systemic therapy. Dual primary endpoints are progression-free survival (PFS) by blinded independent central review (BICR) per RECIST v1.1 and overall survival. A key secondary endpoint is objective response by BICR per RECIST v1.1. Additional secondary endpoints include safety and tolerability, duration of response, PFS and objective response by investigator assessment, and health-related quality of life. The first pt was enrolled in Dec 2025. Clinical trial information: NCT07214779 .
Construction of a whole-course psychological nursing model and its impact on compliance with innovative drug therapy in patients with thoracic tumors: A prospective randomized controlled study.
e13544 Background: Thoracic tumors remain associated with high morbidity and mortality. With advances in precision medicine, novel agents such as Ivosidenib Injection are increasingly used in treatment. However, high cost, prolonged treatment duration, uncertain adverse effects, and concerns about prognosis often lead to anxiety and depression, resulting in poor medication adherence. Under routine nursing, the good adherence rate is only 64.00%, adversely affecting therapeutic outcomes. Therefore, evaluating the value of comprehensive whole-course psychological nursing is necessary. Methods: In this prospective randomized controlled study (May 2024–December 2025), 50 thoracic tumor patients receiving novel drug therapy for the first time were randomly assigned to an observation group or control group (n = 25 each). The control group received routine nursing, while the observation group additionally received four-stage comprehensive whole-course psychological nursing covering admission, preparation, implementation, and recovery periods. Medication adherence, psychological status, and quality of life were assessed using the Morisky Scale, SAS, SDS, and QLQ-C30 at baseline and 4 weeks. Statistical analysis was performed using SPSS 22.0. Results: All patients completed follow-up without adverse events. No significant baseline differences were observed (P > 0.05). After 4 weeks, the observation group showed higher adherence (88.00% vs 64.00%), lower anxiety and depression scores, and better QLQ-C30 functional outcomes than the control group (P < 0.05). Conclusions: Comprehensive whole-course psychological nursing effectively reduces negative emotions, improves adherence to novel drug therapy, and enhances quality of life in thoracic tumor patients, demonstrating substantial clinical value. Integrated core data table. Group Sample Size Post-intervention Good Adherence Rate Post-intervention SAS Score mean±SD Post-intervention SDS Score mean±SD Post-intervention Physical Function Score mean±SD P Value Observation Group 25 88.00 50.13±2.33 54.86±2.10 82.00±5.96 <0.05 Control Group 25 64.00 53.00±2.10 57.73±3.52 74.93±3.13 <0.05 Post-intervention core indicators significant intergroup differences.
ADAPT-M: A tool to predict individualized benefit from adjuvant anti–PD-1 (PD-1) in resected high-risk melanoma.
9567 Background: Resected stage IIB/C and microscopic stage IIIA/B/C/D melanoma presents a significant risk of recurrence risk of 37 to 62% at 5 years (yrs). While 1 year of adjuvant PD1 therapy reduces this risk by approximately half, the individual patient’s baseline risk without treatment and their specific benefit from adjuvant PD1 remain unknown. We aimed to generate two separate predictive models for recurrence – one for untreated and one for treated pts - to calculate the individualised benefit of adjuvant PD1. Methods: Pts with resected stage IIB/C or microscopic stage IIIA/B/C/D melanoma, either treated with adjuvant PD1 or untreated at 13 major melanoma centres, and with at least 2 years of follow-up from surgery were included. We analysed pts demographics, disease characteristics, blood parameters, pathological and imaging data at baseline, and clinical outcomes. Propensity scores were estimated using logistic regression with covariates associated with treatment in univariate screening (p<0.05). Separate penalised multivariable logistic regression models were built to predict recurrence for treated and untreated pts. A tool based on these models was created to calculate the individual patient benefit from adjuvant PD1. Results: A total of 3560 pts was included, divided into untreated (discovery n=2384 and validation n=597) and treated (discovery n=404 and validation n=175) cohorts. The model for untreated pts included age, gender, primary site, histological subtype, Breslow thickness, ulceration, mitosis, number and site of regional lymph nodes (LN), mutation status and LDH (AUC 0.70 in discovery, 0.69 in validation). The model for treated pts included age, gender, Breslow thickness, site of regional LN, and mutation status (AUC 0.69 in discovery, 0.61 in validation). ADAPT-M (ADjuvant Anti-PD-1 Tool for Melanoma) calculates the individualized benefit of adjuvant PD1. For example, patient A, a woman ≤45 years old with a primary head & neck melanoma (superficial spreading, thickness >1-2 mm, no ulceration, 1 mitosis/mm 2 ), 2 clinically occult LN metastases in the neck, NRAS mutant, and normal LDH, has a 12-month recurrence risk of 21.9% untreated vs 2.3% treated (benefit 19.6%), and a 24-month risk of 41.1% untreated vs 6.4% treated (benefit 34.7%). While, patient B, a man ≤45 years old with a primary melanoma in the lower limb (nodular, thickness >1-2 mm, no ulceration, 1 mitosis/mm 2 ), 2 clinically occult LN metastases in the groin, BRAF V600 mutant, and normal LDH, has a 12-month recurrence risk of 14.2% untreated vs 11.8% treated (benefit 2.5%), and a 24-month risk of 28.0% untreated vs 30.1% treated (no benefit). Conclusions: ADAPT-M, a clinical tool that estimate individualized recurrence risks with and without adjuvant anti-PD1 therapy, quantifies the absolute benefit of treatment for pts with high-risk resected melanoma, facilitating personalized adjuvant therapy decisions.
Impact of treatment facility type on survival outcomes in elderly patients with mantle cell lymphoma: A National Cancer Database analysis.
e19067 Background: Mantle cell lymphoma (MCL) is a rare non-Hodgkin lymphoma affecting older adults and associated with poor long-term outcomes despite frontline chemo-immunotherapy (1). Patients aged ≥75 years are underrepresented in clinical trials, and real-world data evaluating outcomes by treatment setting in this population are limited. Using the National Cancer Database (NCDB), we examined differences in treatment patterns and overall survival (OS) among elderly patients with MCL treated at Academic Cancer Programs (ACP) versus Community Cancer Programs (CCP). Methods: We conducted a retrospective cohort study of patients ≥75 years diagnosed with MCL between 2004 and 2022. Patients were stratified by treatment facility type: ACP and CCP. Demographic, socioeconomic, clinical, and treatment variables were compared. Kaplan-Meier analysis and Cox proportional hazards models were used to estimate OS, adjusting for age, race/ethnicity, insurance status, Charlson-Deyo comorbidity score, and distance from the treating facility. Results: A total of 12,167 patients were identified (6,072 treated at ACP and 6,095 at CCP). Median age was 80 years in both cohorts; most were male (66%, p=0.044) and non-Hispanic. Patients treated at ACP resided in metropolitan areas, had higher-income and education levels, and traveled longer distances for care (9.3 vs. 7.7 miles, p<0.001). Medicare was the primary payor in both cohorts (>86%). Across both facility types, more than half of cases presented with advanced-stage lymphoma (stage IV) and comorbidity burden was low (69% of patients had Charlson–Deyo score 0). Patients treated at ACP were slightly more likely to receive active treatment than those treated at CCP (60% vs 57%, p < 0.001). Time to treatment initiation was similar across facility types. Median follow-up was 22 months. OS was longer in patients treated at ACP (median OS 2.5 vs 2.1 years). Two-, five, and ten-year OS rates favored ACP (55% vs 51%; 31% vs 28%; 12% vs 10%; log-rank p<0.001). Conclusions: In this national cohort of patients aged ≥75 years with MCL, OS differed by facility type, with a modest but statistically significant survival advantage at ACPs. These differences may reflect patient selection, access to clinical trials, specialized expertise and multidisciplinary care. Given poor outcomes and limited durability of standard therapies in older adults with MCL, strengthening collaboration between ACP and CCP is critical to improving access to high-quality care and novel strategies. Prospective studies are warranted to validate these findings and improve equity and outcomes in this vulnerable population.
Trial growth and accessibility: Enrollment-weighted access to U.S. lung cancer clinical trials (2015–2025).
e23116 Background: Although U.S. lung cancer trials have expanded over the past decade, trial counts alone may overestimate patient access when enrollment capacity is geographically concentrated. We developed an enrollment-weighted Trial Desert Index (eTDI) to measure patient-facing research opportunity and test whether growth in trial activity translated into equitable access. Methods: We identified U.S. interventional lung cancer trials registered on ClinicalTrials.gov and active from 2015 – 2025. Target enrollment was allocated across each trial’s active years and participating states using a systematic trial-to-state site mapping audit. eTDI was defined as enrollment slots per incident lung cancer case, reflecting patient-level opportunity. State-level five-year survival and early-stage diagnosis rates were examined to evaluate alignment with access. We quantified geographic concentration (Top-10 state share; Gini coefficient), identified high-burden/low-access states via incidence-eTDI percentile misalignment, and compared patterns by funder type. Results: By 2025, annualized U.S. lung trial enrollment capacity reached 74,093. Enrollment-weighted access was highly centralized, with the top 10 states accounting for 73.3% of enrollment capacity (Gini coefficient 0.693). The top five states were Florida (19.2%), Ohio (18.9%), California (6.7%), New York (6.4%), and Texas (4.4%). High-incidence states including Georgia, Illinois, Indiana, South Carolina, Wisconsin, and Louisiana demonstrated pronounced burden-access misalignment with persistently low enrollment-weighted access. Non-industry trials exhibited greater geographic concentration than industry-sponsored trials, with a top-10 state share of 82.5% versus 57.4%. Across states, lower eTDI frequently co-occurred with poorer publicly reported five-year survival or early-stage diagnosis rates. Conclusions: Despite substantial trial growth, enrollment-weighted access remains highly concentrated and poorly aligned with disease burden, limiting availability in high-incidence states. Metrics such as eTDI provide a reproducible framework for benchmarking access across trial networks, informing site decentralization, and enabling funder accountability to better align research capacity with population need. Enrollment-weighted lung trial access by selected states (2025). State Burden Enrollment Share (%) eTDI (Access) FL High 19.2 High OH High 18.9 High CA High 6.7 High NY High 6.4 High GA High 0.8 Low IL High 1.4 Low IN High 0.6 Low LA High 0.2 Low Selected high-incidence states illustrating heterogeneity in enrollment-weighted lung cancer trial access in 2025.
T320 tissue factor-targeted ADC from pre-clinical research to phase I clinical study.
e15032 Background: Tissue factor (TF) is highly expressed in various malignant tumors, including pancreatic, cervical, lung, and esophageal cancers, while being minimally expressed in normal tissues. T320 is a novel antibody-drug conjugate (ADC) consisting of a TF-targeting humanized monoclonal IgG1 conjugated with the cytotoxic payload monomethyl auristatin E (MMAE). Methods: Preclinical evaluation included in vitro binding affinity assays using TF-expressing tumor cell lines and in vivo efficacy studies in multiple human tumor xenograft models to assess tumor growth inhibition. GLP-compliant toxicology and safety studies were conducted in cynomolgus monkeys, administering T320 at doses up to 5 mg/kg weekly for five weeks (QWx5W) to evaluate systemic toxicity. Based on these GLP non-clinical studies, a non-randomized, open-label, multicenter Phase I clinical study was launched to evaluate the safety, tolerability, and pharmacokinetics (PK) of T320 in patients with advanced solid tumors. Results: In vitro studies demonstrated that T320 has a high affinity for its tumor cell target. In vivo efficacy studies showed over 90% inhibition of tumor growth, and toxicology studies in monkeys revealed no serious systemic toxicity at doses up to 5 mg/kg QWx5W. As of December 2025, 9 patients have been enrolled in the Phase I study. Preliminary clinical PK analysis and adverse drug reactions (ADRs) have been assessed; notably, one patient with ovarian cancer in the 0.4 mg/kg Q3W cohort achieved durable stable disease for 6 months. The most common ADRs (occurring in at least 20% of patients) included hypoalbuminemia, anemia, increased blood bilirubin, gastrointestinal bleeding, coagulation disorder, constipation, nausea, and fatigue. Conclusions: Preclinical studies have demonstrated the potent anti-tumor efficacy and favorable pharmacokinetics and safety profile of T320. Early clinical data indicate manageable toxicity and promising activity, specifically highlighted by the durable stable disease observed in ovarian cancer. Further evaluation of T320 performance in the ongoing Phase I clinical study is expected.
Patient-reported outcomes (PROs) and health-related quality of life (HRQoL) with taletrectinib in advanced ROS1+ non-small cell lung cancer (NSCLC) from the TRUST-II study.
8629 Background: Taletrectinib is a next-generation, CNS-active, selective ROS1 tyrosine kinase inhibitor (TKI) approved by the US FDA for the treatment of patients with locally advanced or metastatic ROS1+ NSCLC based on results from two Phase 2 studies, TRUST-I (NCT04395677) and TRUST-II (NCT04919811). Here we report PROs with taletrectinib from TRUST-II. Methods: Patients with locally advanced or metastatic ROS1+ NSCLC were treated with taletrectinib 600 mg once daily in 21-day cycles. HRQoL and PROs for cancer-specific symptoms were evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 30-item core module (QLQ-C30) and 13-item lung cancer module (QLQ-LC13). Questionnaires were only distributed to patients from North America and Europe. Data were collected at screening, then subsequently on Day (D)1 of every cycle (C) until C9D1, on D1 of every three cycles until C27D1, and every four cycles thereafter until the end of treatment (within 7 days of last dose). Changes from baseline over time were summarized using descriptive statistics. A change in score of ≥10 points from baseline was considered clinically meaningful. Time to first improvement (TFI) was assessed using Kaplan–Meier methods. Results: At data cutoff (August 31, 2025), the analysis set included 69 patients (23 TKI-naïve and 46 TKI-pretreated). Mean changes from baseline improved or remained stable for most domains across both questionnaires. For global health status/quality of life, the majority of patients showed clinically meaningful improvement or remained stable at multiple timepoints assessed (e.g. 74% of patients at C7). Mean cognitive function score improved or remained stable throughout treatment, with the majority (63–77%) of patients showing improvement or stability and only 9–23% of patients showing worsening at various assessment times. Common disease-related symptoms, including pain and fatigue (QLQ-C30), and dyspnea and coughing (QLQ-LC13), showed consistent clinically meaningful improvement throughout treatment, with a median TFI of 1–3 months across all patients. Coughing was particularly improved in TKI-naïve patients, with a median TFI of < 1 month. Conclusions: Taletrectinib was associated with improved or stable HRQoL in the majority of patients and with rapid relief of disease-related symptoms. In contrast to other ROS1 TKIs, taletrectinib demonstrated preservation of cognitive function over time. Together with the efficacy and safety results, these data further support the use of taletrectinib for patients with ROS1+ NSCLC. Clinical trial information: NCT04919811 .
Efficacy and safety of adding S-1 to chemotherapy regimens in advanced gastric cancer: A meta-analysis.
e16074 Background: Gastric cancer (GC) remains a major global health burden, ranking as the fifth most commonly diagnosed malignancy and the fifith leading cause of cancer-related mortality worldwide. Due to the lack of population-based screening programs, early detection is difficult and most patients are diagnosed with advanced disease, for whom curative treatment options are limited. S-1 is an oral fluoropyrimidine that has demonstrated encouraging efficacy and safety profiles for Advanced GC (AGC) S-1-containing regimens by several randomized controlled trials (RCTs). This review aims to evaluate whether S-1-based chemotherapy regimens improve survival and disease progression outcomes in AGC patients compared with non-S-1 strategies. Methods: A systematic search was conducted in the Medline, Cochrane, and Web of Science databases were systematically searched for RCTs comparing S-1 containing regimens with other treatments without S-1 in patients diagnosed with AGC. The assessed outcomes included Progression-Free Survival (PFS), Overall Survival (OS), Overall Response Rate (ORR), Disease Control Rate (DCR), Time to Progression (TTP), Time to Treatment Failure (TTF), as well as all grades and ≥ 3 grade Adverse Events (AEs). The assessed outcomes with 95% Confidence Intervals (CI) were estimated using random-effects models. Heterogeneity among studies was assessed using the I² statistic. Statistical analyses were performed using RStudio 4.4.2. Results: A total of 20 RCTs encompassing 3,181 patients were included in the meta-analysis, from whom 1,665 received S-1-containing regimens and 1,516 received control treatments. The pooled analysis demonstrated a statistically significant improvement in PFS (HR: 0.8778; 95% CI: 0.7855-0.9808; p: 0.02; I²: 38.3%) and OS (HR: 0.9260; 95% CI 95%: 0.8595-0.9976; p: 0.04; I²: 0.0%) in S-1 containing treatments. Regarding tumor response outcomes, no statistically significant differences were observed in ORR (OR: 1.17; 95% CI: 0.86-1.58; p: 0.31; I²: 62.5%) and DCR (OR: 1.18; 95% CI: 0.92-1.53; p: 0.22; I²: 0%). Time-to-event secondary endpoints showed a significant prolongation of TTF (HR: 0.83; 95% CI: 0.74-0.94), whereas no significant difference was observed in TTP (HR: 1.04; 95% CI: 0.85-1.26). Conclusions: S-1-containing regimens improved PFS and TTF and showed a borderline OS benefit without increasing adverse events, although no significant differences were observed in tumor response outcomes.These findings suggest that S-1-based strategies for AGC patients may offer a modest survival benefit without increased toxicity.
Tislelizumab plus cetuximab and irinotecan in relapsed/refractory RAS/BRAF wild-type and microsatellite stable metastatic colorectal cancer: A randomized, controlled, multicenter study (TEC2).
3530 Background: Under suboptimal efficacy and safety of current third-line standard-of-care (SoC), several single-arm studies have demonstrated that anti-PD-(L)1 antibodies plus EGFR inhibitors with or without chemotherapy may be valuable for relapsed/refractory RAS/BRAF wild-type and microsatellite stable metastatic colorectal cancer (R/R RAS/BRAF WT and MSS mCRC). This study aimed to compare tislelizumab (anti-PD-1 antibody) plus cetuximab and irinotecan as third- or later-line therapy versus investigator-selected SoC for R/R RAS/BRAF WT and MSS mCRC. Methods: This was a randomized controlled, open-label, multicenter study (NCT05278351). Eligible patients were aged ≥18 years with histologically confirmed RAS/BRAF WT and MSS metastatic colorectal adenocarcinoma who failed ≥2 prior lines of systemic therapy. Patients were randomly assigned (2:1) to receive intravenous tislelizumab (200 mg) plus cetuximab (500 mg/m 2 ) and irinotecan (180 mg/m 2 ) on days 1 and 15 or investigator-selected SoC (fruquintinib, regorafenib, or TAS-102) in a 4-week cycle until disease progression, unacceptable toxicity, or other protocol-defined reasons. Primary end point was progression-free survival (PFS). Secondary end points included objective response rate, disease control rate, duration of response, overall survival, and safety. Results: Eighty-seven patients (median age, 62.0 years; 59 [67.8%] men) were enrolled between July 2022 and March 2024, randomized, and assessed for efficacy; one patient did not receive the triplet regimen and was removed from the safety population. With median follow-up of 26.1 months (95% confidence interval [CI]: 22.4-28.4) by data cutoff (June 30, 2025), median PFS was 4.4 months (95% CI, 3.8-6.6) in the tislelizumab-cetuximab-irinotecan group and 2.0 months (95% CI, 1.9-5.4) in the SoC group (Breslow-Gehan P =0.009). Landmark analysis at a cutoff point of 10 months showed a significantly extended PFS with tislelizumab plus cetuximab and irinotecan versus SoC (HR 0.37 [95% CI, 0.21-0.64]; p<0.001). Grade ≥3 treatment-related adverse events (TRAEs) occurred at comparable frequencies in the two groups (15.8% vs 17.2%). No TRAEs led to death. Conclusions: Tislelizumab plus cetuximab and irinotecan as third- or later-line therapy appeared feasible and safe for patients with R/R RAS/BRAF WT and MSS mCRC. Clinical trial information: NCT05278351 . Tislelizumab-cetuximab-irinotecan (n=58) SoC (n=29) Best response Complete response 0 0 Partial response 12 (20.7) 1 (3.4) Stable disease 32 (55.2) 12 (41.4) Disease progression 11 (19.0) 16 (55.2) Not evaluable 3 (5.2) 0 Objective response 12 (20.7) 1 (3.4) Disease control 44 (75.9) 13 (44.8) 6-month PFS rate, % (95% CI) 38.2 (27.3-53.5) 20.4 (9.6-43.7)
T-Bren (BL-M07D1) in patients with recurrent or metastatic (R/M) ovarian cancer: Results from two phase II studies.
3003 Background: T-Bren is a HER2-directed antibody-drug conjugate (ADC) consisting of an anti-HER2 monoclonal antibody linked to a potent topoisomerase I inhibitor (Ed-04). In phase I studies, T-Bren demonstrated encouraging anti-tumor activity with a manageable safety profile in patients (pts) with solid tumors. Results of safety/efficacy from two phase II studies in pts with R/M ovarian cancer (OC) are presented. Methods: Two studies evaluated T-Bren as monotherapy in pts with R/M platinum-resistant (disease progression within 6 months of the last dose of platinum-based chemotherapy) and platinum-sensitive OC. Pts with R/M OC were treated at 3.8mg/kg or 4.4mg/kg D1 Q3W. Primary endpoints include ORR and RP2D. Pts were selected for HER2 expression (ultra-low/1+/2+/3+). Results: As of Nov 30, 2025, a total of 65 pts were enrolled at 3.8 (N = 51), or 4.4mg/kg (N = 14) D1Q3W. Of all pts, 28 (43.1%) pts previously received ≥3 lines of therapy. The most common grade 3 and above hematologic TRAEs were thrombocytopenia (41.5%), leukopenia (35.4%), neutropenia (35.4%), and anemia (29.2%); the most common grade 3 and above non-hematologic TRAEs were asthenia (6.2%), lymphocyte count decrease (6.2%). Grade 3 and above TRAEs, which were predominantly hematologic in nature, were able to be effectively managed with standard supportive measure including dose reductions, as demonstrated by the TRAE leading to discontinuation rate of 3.1%. No ILD was observed. No new safety signals were identified. Median follow-up was 7.8 mo. Among pts at 3.8mg/kg D1 Q3W, confirmed ORR (cORR) was 88.9% in platinum-sensitive OC and 47.5% in platinum-resistant OC. mPFS had not reached and 9-mo PFS rate was 85.7% in platinum-sensitive OC and 61.2% in platinum-resistant OC. Efficacy results are summarized in the table below. Conclusions: T-Bren has demonstrated promising anti-tumor activity with a manageable safety profile in heavily pre-treated pts with R/M OC. Dose 3.8mg/kg D1 Q3W was chosen as the RP3D. Phase III study of platinum-resistant OC is in preparation. Clinical trial information: NCT06031584; NCT06131450 . Total (N=63) 3.8mg/kgTotal (N=49) 3.8mg/kgPlatinum-sensitive (N=9) 3.8mg/kgPlatinum-resistant(N = 40) Median prior LoT (range) 2 (1-8) 2 (1-6) 2 (1-4) 2 (1-6) ORR, % (95% CI) 57.1 (44.0, 69.5) 59.2 (44.2, 73.0) 88.9 (51.8, 99.7) 52.5 (36.1, 68.5) cORR, % (95% CI) 49.2 (36.4, 62.1) 55.1 (40.2, 69.3) 88.9 (51.8, 99.7) 47.5 (31.5, 63.9) DCR, % (95% CI) 88.9 (78.4, 95.4) 89.8 (77.8, 96.6) 100 (66.4, 100) 87.5 (73.2, 95.8) mPFS (mo) (95% CI) 9.3 (7.0, NR) NR (7.0, NR) NR (5.6, NR) NR (7.0, NR) 9-mo PFS rate, % (95% CI) 50.1 (24.0, 71.6) 67.5 (46.0, 81.9) 85.7 (33.4, 97.9) 61.2 (34.5, 79.7) *All pts who received at least one dose of T-Bren, excluding those still ongoing with insufficient follow up were used for efficacy analysis.
Choice and impact of EQ-5D-5L value set in cost-utility analyses alongside multinational trials: Insights from PREFERABLE-EFFECT and CONVINCE
Objectives Multinational clinical trials are increasingly common in the European Economic Area, yet no guideline exists on which EQ-5D value set(s) should be used for health economic evaluations alongside multinational trials. Either a single value set or country-specific value sets can be applied, and previous studies have shown that the choice of value set can impact the estimated utility scores. For the EQ-5D-5L, the impact on European pooled cost-utility analyses has not been established. This study evaluates the impact of EQ-5D-5L value sets on cost-utility outcomes in two multinational trials. Methods Data from two multinational randomized controlled trials were used: (i) supervised exercise compared to usual care for patients with metastatic breast cancer (PREFERABLE-EFFECT), (ii) hemodiafiltration compared to hemodialysis for patients with kidney failure (CONVINCE). EQ-5D-5L was assessed at baseline and during follow-up. Utility scores and quality-adjusted life years (QALYs) were calculated with the country-specific value set for each participant, and with the value set of each included country. The probability of cost-effectiveness was estimated using bootstrapping. Results Mean assigned utility scores per year alive ranged between 0.762 and 0.889 for PREFERABLE-EFFECT, and 0.673 and 0.806 for CONVINCE. The difference in utility scores is largest when participants report low quality of life. Estimated QALY gains ranged between 0.013 and 0.020 for PREFERABLE-EFFECT and 0.045 and 0.058 for CONVINCE. The maximum difference in probability of cost-effectiveness between the value sets was Δ8.3% at €80,000/QALY in PREFERABLE-EFFECT, and Δ11.1% at €40,000/QALY for CONVINCE. Conclusions Choice of value set led to substantial variation in absolute utility scores and QALYs, which may influence cost-utility outcomes. This impact could be greater when an intervention prevents or aids recovery of health conditions associated with low quality of life, or results in large mortality differences. Scenario analyses using multiple value sets should be conducted for multinational trials.
The Power of Pnictogen Bond: As─As Linkages Drive Wide Bandgap, Strong NLO Response and Large Birefringence in SrGa <sub>3</sub> Si <sub>4</sub> As <sub>11</sub>
ABSTRACT Arsenides represent an advantageous platform for designing long‐wavelength infrared (IR) nonlinear optical (NLO) materials; however, the intrinsic narrow bandgaps hinder their applications. In this work, by introducing As–As homoatomic bonds to eliminate the nonbonding electron pairs on As atoms, the first experimentally verified quaternary arsenide NLO material SrGa 3 Si 4 As 11 was rationally designed within the As‐rich A II –B III –C IV –As system, and synthesized experimentally. The compound crystallizes in the uniaxial hexagonal system ( P 6 3 space group, No. 173) and is composed of [SrAs 9 ] polyhedra, [GaAs 4 ] and [SiAs 4 ] tetrahedra with unique As–As homoatomic bonding. The introduction of As─As bonds simultaneously enhances the NLO response, bandgap, and birefringence, demonstrating a strong phase‐matching second‐order NLO response (∼8.0 × AgGaS 2 ), a wide arsenide bandgap (∼1.59 eV), a high laser‐induced damage threshold (∼1.5 × ZnGeP 2 and ∼4.0 × AgGaS 2 ) and a large birefringence (Δ n = 0.10@2090 nm) in the compound. Both experimental and theoretical results confirm the positive contributions of As─As bonds to these superior properties. The results enrich the structural diversity of arsenides, and establish As‐rich arsenides incorporating homoatomic bonds as an emerging system for high‐performance IR NLO materials, with SrGa 3 Si 4 As 11 serving as a promising candidate.
A controlled approach to optimising nanoparticle retention in porous media using retained particle distribution
Heteroatom‐Engineered Triatomic Cu Cluster on G‐C <sub>3</sub> N <sub>4</sub> for Selective CO <sub>2</sub> ‐to‐Ethylene Electrocatalysis
ABSTRACT Electrochemical reduction of CO 2 into multi‐carbon products offers a sustainable route to carbon recycling, yet achieving selective C─C coupling remains challenging. Here, we investigate the performance of heteroatom‐doped Cu 3 clusters supported on g‐C 3 N 4 for CO 2 ‐to‐C 2 H 4 conversion. Through DFT calculations and transition‐state analysis, we demonstrate that doping with P and Se stabilizes the Cu 3 clusters, enhances * CO adsorption, and lowers the energy barrier for the rate‐determining * CO + * CHO → * COCHO C─C coupling step to 0.84 and 0.92 eV, respectively. Thermodynamic analysis reveals a preference for ethylene formation over ethanol, with overpotentials as low as 0.33 and 0.10 V for P‐ and Se‐doped systems. Electronic structure analysis shows that first‐shell substitution with P or Se creates charge‐asymmetric sites, strengthens * CO and * CHO binding, and shifts antibonding Cu─CO states to higher energies, thereby promoting efficient C─C coupling. Electrochemically, the Se‐modified catalyst delivers a remarkable ethylene Faradaic efficiency of ∼54% at 250 mA cm −2 , and maintains stable performance for 30 h under flow‐cell conditions. This study establishes a synergistic theory‐experiment framework for optimizing CO 2 RR catalysts, emphasizing the critical role of precise cluster engineering and charge‐gradient doping in promoting efficient C─C coupling.