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Safety and efficacy results of the phase 2 study of silevertinib (BDTX-1535) in treatment-naïve patients with non-small cell lung cancer with non-classical EGFR mutations.

8519 Background: Non-classical mutations (NCM) of epidermal growth factor receptor (EGFR) represent a broad group of oncogenic mutations in non-small cell lung cancer (NSCLC), often associated with resistance to osimertinib (e.g., P-loop and αC-helix compressing [PACC] mutations). Patients (pts) with NCM have inferior clinical outcomes with a high incidence of CNS metastases (CNSm). Silevertinib (BDTX-1535) is a fourth-generation, covalent EGFR TKI with high CNS penetrance targeting both EGFR classical mutations and NCM. The antitumor activity and safety of silevertinib in pts with advanced NSCLC were evaluated in a Phase 2 trial (NCT05256290). Methods: Pts with advanced EGFR NCM NSCLC who received no prior systemic therapy were enrolled (Cohort 3) based on a local molecular test. Silevertinib 200 mg was administered orally once daily. The primary endpoint of objective response rate (ORR) was assessed using RECIST v1.1. CNS ORR was assessed using Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM) in pts with no prior CNS therapy. Secondary endpoints include progression-free survival (PFS), duration of response (DOR), disease control rate (DCR), and safety. Results: From February 2024 to July 2025, 43 pts with 35 unique NCMs (including 25 pts with PACC mutations) were enrolled in Cohort 3: median age 70.0 years, 72% female, 74% white, and 42% never smoked cigarettes. As of November 3, 2025, median follow-up was 7.2 months. ORR by RECIST v1.1 is shown in the table. Sixteen pts (37%) had CNSm, including 7 pts (16%) with measurable CNS disease. RANO-BM CNS response was 86% (n=6/7). Complete clearance of EGFR VAF ctDNA was observed in 21/26 (81%) evaluable pts. Serious treatment-related adverse events (TRAEs) were reported in 5 pts (12%), and 4 pts (9%) discontinued treatment due to TRAEs. The most common TRAEs included rash (19%, grade 3), diarrhea (19%, grade 3), stomatitis (9%, grade 3), and paronychia (5%, grade 3). While 77% of pts had a dose reduction, 19/22 (86%) patients with a radiographic response maintained or deepened their response after dose reduction, including all patients with CNS response. Conclusions: Silevertinib demonstrated robust antitumor activity in treatment-naïve pts with a broad spectrum of NCM EGFR driver mutations with high intracranial activity in pts with brain metastases. The safety profile was consistent with the known AEs of the EGFR TKI class. Clinical trial information: NCT05256290 . Data as of November 3, 2025 N ORR n (%) 95% CI DCR n (%) 95% CI ITT Population * 43 26 (60) (44.4, 75.0) 39 (91) (77.9, 97.4) PACC mutations 25 14 (56) (34.9, 75.6) 22 (88) (68.8, 97.5) Compound mutations † 16 11 (69) (41.3, 89.0) 15 (94) (69.8, 99.8) *No pts with classical (E746_A750del or L858R) mutations were enrolled. † Presence of ≥ 2 NCMs. As of December 27, 2025, the 6-month PFS rate was 86% overall and 80% in pts with CNSm; available PFS and DOR data will be presented.

A phase II, single-arm study of romiplostim N01 for cancer treatment–induced thrombocytopenia in leukemia patients.

6550 Background: Cancer Treatment-Induced Thrombocytopenia (CTIT) poses a significant challenge in leukemia treatment, increasing bleeding risk and potentially disrupting therapy. Romiplostim N01 is recommended for CTIT but lacking specific clinical data in leukemia patients. This study evaluates its efficacy and safety in this population. Methods: This is a multi-center, single-arm, phase II study conducted from February 2025 to February 2027. We plan to enroll 97 adult patients (18 - 75 years) with leukemia who developed CTIT (platelets < 50×10⁹/L) after antitumor therapy. Patients received subcutaneous Romiplostim N01 at a starting dose of 5 µg/kg once weekly for up to 8 weeks. The primary endpoint is the proportion of patients achieving platelet recovery (≥ 50×10⁹/L) after two week. Secondary endpoints include response rate within 7 days, median time to platelet recovery (≥ 50×10⁹/L and ≥ 100×10⁹/L), platelet transfusion requirements, and safety. Results: As of January 27, 2026, a total of 49 subjects were enrolled (18 males, 31 females) with a median age of 57 years (range, 17–75). Primary tumor types included acute myeloid leukemia (AML, n=40), acute lymphoblastic leukemia (ALL, n=7), mixed phenotype acute leukemia (MPAL, n=1), and myelodysplastic syndromes (MDS, n=1). All patients received standard chemotherapy and had an ECOG performance status of 0–2 at enrollment; 35 of 49 patients had an ECOG score of 0–1. All subjects received Romiplostim N01 (5 µg/kg/week): 13 subjects received one dose, 14 received two doses, and 22 received ≥ 3 doses. The median baseline platelet count was 15×10⁹/L (range, 1–49×10⁹/L). 40.8% (20/49) of patients achieved a response within 7 days. 23 subjects (46.9%, 23/49) achieved the primary endpoint (platelet count ≥ 50×10⁹/L) within two weeks. The median time to platelet recovery ≥ 50×10⁹/L was 7 days (95% CI, 6–9). A total of 21 patients achieved a platelet count of ≥100×10⁹/L; the median time to recovery was 13 days (95% CI, 10–22). The median platelet transfusion dose was 2.0 units (95% CI, 1–3). Adverse events were mild to moderate, most commonly infections. No treatment-related serious adverse events (SAEs) were reported. Conclusions: Preliminary findings suggest Romiplostim N01 may be effective in promoting platelet recovery with a manageable safety profile in leukemia patients with CTIT. Final results will provide further evidence for its clinical application. Clinical trial information: NCT06898983 .

Outpatient rehabilitation for adults with soft tissue sarcoma: Examining real-world service utilization and outcomes.

11563 Background: Soft tissue sarcoma (STS) and its treatments frequently result in substantial physical morbidity, leading to impaired function and reduced quality of life. Rehabilitation can improve outcomes, yet real-world utilization and effectiveness in this population remain poorly understood. This study describes outpatient rehabilitation service use among adults with STS and examines changes in physical function and quality-of-life outcomes. Methods: Electronic medical record data from outpatient rehabilitation encounters were retrospectively analyzed for adults with a STS diagnosis (identified by ICD code) who completed ≥2 visits and had pre- and post-treatment outcome measures available. Rehabilitation characteristics were examined descriptively, including visits, care duration, service type, and treatment indications (identified by ICD code). PROMIS-Physical function (PF) was the primary outcome. Secondary outcomes were PROMIS-Global physical health (GPH), -Ability to participate in social roles and activities (SRA), and -Global mental health (GMH). Mixed-effect models assessed change in T-scores, adjusting for covariates (age, visits per week, care duration) and accounting for within-subject correlation. Estimated marginal (EM) means are reported. Change scores were compared to the established minimal important change (MIC, 2 points) to determine clinical relevance. Results: A total of 151 patients met inclusion criteria (mean age 56.0±16.7 years; 57% female). Most received physical therapy (86.1%), with fewer receiving occupational therapy (13.2%). The median episode of care was 8.3 weeks (IQR 4.3–16.0), with a mean of 1.6± 0.7 visits per week. Common treatment indications included pain (37.9%), weakness/deconditioning (35.8%), gait/balance (27.5%), followed by lymphedema (8.5%), fatigue (5.9%), wound/post-surgery care (5.5%), and neuropathy (3.1%). Significant improvements were observed in PF (+2.48, SE: 0.57), GPH (+2.64, SE: 0.50), and SRA (+2.64, SE: 0.57) (p<.001), each surpassing the MIC. No significant change was observed in GMH (-0.39, SE:0.48, p=.419). Conclusions: In this real-world cohort of adults with STS, outpatient rehabilitation averaged 8 weeks of care and 1-2 visits per week, most commonly addressing pain, weakness, and gait/balance deficits. Significant and clinically meaningful improvements were observed in physical function and the physical and social aspects of quality of life; mental health was not significantly affected. These findings support the role of rehabilitation as an important component of multidisciplinary sarcoma care and underscore the need for complementary strategies to address psychosocial outcomes. PROMIS T-scores, EM mean (SE). Outcome Pre Post PF 36.26 (0.50) 38.74 (0.57) GPH 39.44 (0.52) 42.08 (0.56) SRA 43.17 (0.56) 45.82 (0.65) GMH 47.40 (0.60) 47.02 (0.63)

Structural disparities in early-onset colorectal cancer mortality: A national county-level analysis.

10579 Background: Early-onset colorectal cancer (CRC) incidence and mortality are rising, with significant disparities by geography and socioeconomic status. We examined county-level disparities in early-onset CRC mortality (ages < 55) across the United States to identify modifiable factors associated with mortality rates. Methods: We analyzed age-adjusted CRC mortality rates from CDC WONDER. Predictors included rurality (Rural–Urban Continuum Codes 2023: non-metro vs metro), socioeconomic factors (median income, % uninsured, % poverty from County Health Rankings 2025), demographic composition (% non-Hispanic Black, % Hispanic), health behaviors (current smoking, obesity, routine checkup from PLACES 2025), and healthcare access (gastroenterologist, primary care physician, and hospital counts from AHRF 2024–2025). Multivariable linear regression assessed associations between predictors and mortality, with continuous variables standardized to z-scores. Counties with missing or unreliable mortality data were excluded (p < 0.05 for significance). Results: The final sample included 672 counties. Mean mortality was 4.26 per 100,000 (range 1.7–11.9). Non-metro counties comprised 12.2% (n = 82). The model explained 54.8% of variance in mortality (F = 66.5, p < 0.001). Current smoking was the strongest predictor (β = 0.54 per SD, 95% CI: 0.38–0.70, p < 0.001), indicating a one-SD increase in smoking prevalence corresponded to a 0.54 per 100,000 higher mortality rate. Non-metro counties had 0.80 more deaths per 100,000 than metro counties (95% CI: 0.56–1.05), a 19% increase relative to the mean. Poverty (β = 0.21 per SD, p = 0.011), uninsured rates (β = 0.20 per SD, p < 0.001), and % Black (β = 0.21 per SD, p < 0.001) were also significant. Higher Hispanic population was associated with lower mortality (β = −0.20 per SD, p = 0.001). Healthcare provider variables (gastroenterologist count, primary care count, hospital count) were not significantly associated (p≥0.051). Conclusions: Geographic, socioeconomic, and health behavior factors accounted for 54.8% of variation in early-onset CRC mortality, with smoking showing the strongest association. Non-metro counties and areas with higher poverty, uninsured rates, and smoking prevalence had higher mortality, though these relationships are not causal. Remaining unexplained variance suggests roles for screening uptake, stage at diagnosis, treatment quality, and genetic susceptibility. Findings identify high-risk counties and highlight the need for future causal analyses to clarify pathways underlying disparities and support targeted interventions.

Real-world outcomes of olaparib with versus without bevacizumab in bevacizumab-naïve BRCA1/2-mutated ovarian cancer.

5574 Background: For patients with BRCA1/2-mutated epithelial ovarian, fallopian tube, or primary peritoneal cancer who complete primary platinum-based therapy, maintenance strategies differ based on prior bevacizumab (Bev) exposure. Patients who received Bev during frontline platinum therapy may receive Bev plus olaparib, whereas those without prior Bev exposure are generally treated with olaparib alone. No real-world evidence has evaluated outcomes of adding Bev to olaparib in patients who did not receive Bev during initial treatment. Using a large multi-institutional electronic health record dataset, we compared survival outcomes between olaparib monotherapy and olaparib–Bev combination therapy in this population. Methods: Adult patients from 2015-2024 with a diagnosis of ovarian, fallopian tube, or peritoneal cancer who received platinum chemotherapy followed by olaparib were first identified. Patients were then categorized based on bevacizumab exposure around the time of olaparib initiation (-1 to +3 months). This group was compared to patients who did not received Bev at any time. The index date was defined as 3 months after olaparib initiation to align treatment timing and minimize immortal time bias and propensity score matching was performed on age, race, metastatic sites, comorbidities, and prior treatments. Follow-up was then truncated at 3-years. Results: Before matching, 111 patients received Bev around the time of olaparib and 1,461 did not. After matching, 110 patients remained in each group with balanced characteristics. Three-year overall survival was significantly lower in the Bev group compared with the no-Bev group (52% vs 73%; HR 2.28, 95% CI 1.4–3.8; p=0.001). Treatment switching also occurred more often in the Bev group (54% vs 22%, p < 0.0001), with a median time to switching of 16.7 months; the no-Bev group did not reach median time. Conclusions: In real-world clinical practice, the addition of bevacizumab to olaparib in patients without prior bevacizumab exposure was associated with worse survival outcomes and earlier treatment switching. These findings may reflect the selection of patients with more aggressive or treatment-resistant disease for combination therapy, or they may suggest that intensifying therapy in this setting does not confer added benefit. Prospective, controlled studies are needed to clarify the underlying reasons for these observations and to better define which patients, if any, derive benefit from this treatment approach.

Attention-driven vision transformer analysis for automated melanoma diagnosis using dermoscopy.

e21532 Background: Melanoma is an aggressive skin cancer with rapidly rising incidence and disproportionately high mortality when diagnosed at advanced stages. Dermoscopy improves diagnostic accuracy but remains highly operator dependent, with substantial interobserver variability, particularly for early or atypical lesions. Although convolutional neural networks (CNNs) have demonstrated strong performance in automated skin lesion analysis, their reliance on localized receptive fields may limit modeling of global lesion characteristics—such as asymmetry, border irregularity, and spatial color heterogeneity—that are central to melanoma diagnosis. Vision Transformers (ViTs) introduce an alternative paradigm based on self-attention, enabling global contextual reasoning across entire images. We evaluated a Vision Transformer B/16 (ViT-B/16) model for automated melanoma diagnosis using dermoscopic imaging. Methods: We analyzed publicly available dermoscopy datasets from established melanoma imaging repositories, including the ISIC Archive and HAM10000 collections, comprising malignant melanoma, non-melanoma skin cancers, and benign melanocytic lesions with histopathologic confirmation or expert consensus annotation. Images were standardized, augmented, and stratified into training and validation cohorts. A ViT-B/16 model pretrained on ImageNet was fine-tuned for multi-class lesion classification. Input images (224×224) were partitioned into non-overlapping 16×16 patches and embedded into a token sequence with positional encodings and a learnable class token. The architecture employed 12 transformer encoder blocks with multi-head self-attention and feed-forward layers. Performance was assessed using accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUROC). Results: The Vision Transformer achieved strong diagnostic performance, with overall accuracy exceeding 97% and AUROC greater than 0.97 across lesion categories. Attention-based global modeling improved discrimination of melanomas with asymmetric structure, heterogeneous pigmentation, and irregular borders—features commonly associated with diagnostic uncertainty. Performance remained stable across lesion subtypes and imaging conditions and was comparable to state-of-the-art CNN-based approaches. Conclusions: Vision Transformer–based modeling enables accurate and interpretable melanoma classification by capturing global dermoscopic context beyond localized feature extraction. Although computationally more intensive than conventional CNNs, ViT architectures offer complementary strengths for modeling complex lesion morphology and warrant further evaluation for integration into melanoma screening and AI-assisted dermatologic workflows.

Intermittent fruquintinib plus trifluridine/tipiracil in refractory metastatic colorectal cancer (mCRC): A single-center, single-arm phase II study.

e15560 Background: A phase II study suggested that the combination of fruquintinib (Fru) and trifluridine/tipiracil (TAS-102) could prolong progression-free survival (PFS) and overall survival (OS). However, the benefits are limited due to tolerability associated with continuous administration. This study aimed to explore the efficacy and safety of intermittent administration of Fru and TAS-102 as a 3L treatment for mCRC patients(pts). Methods: This was a single-center, single-arm, phase II study (ChiCTR2300078241). The primary endpoint was objective response rate (ORR). Secondary endpoints included PFS, OS, disease control rate (DCR), and safety. The ORR was set to ≤1% in the null hypothesis using a two-sided αof 0.05. To reject the null hypothesis and achieve an expected ORR of 10% with an 80% power, a minimum of 29 pts was required. Considering a dropout rate of 15%, the study planned to enrol 35 mCRC pts who had failed two standard treatment regimens. Eligible pts received oral Fru (3 mg, once daily, on days 1-5 and 8-12) and TAS-102 (35 mg/m², twice daily, on days 1-5) every two weeks until disease progression or unacceptable toxicity occurred. Results: A total of 35 pts were enrolled between August 2023 and March 2025. The median age was 58 years (range: 19-77). RAS mutations were present in 54.3% of pts, 62.9% had left-sided colon or rectal cancer, 54.3%, 40.0% and 45.7% had liver metastases, peritoneal metastases and multiple metastases respectively. As of December 15, 2025, 33 pts had discontinued study treatment and 2 pts were ongoing treatment. The ORR and DCR were 11.4% (4/35) and 80.0% (28/35) respectively. The median PFS (mPFS) was 7.2 (95% CI: 5.0–9.4) months(m), and median OS was 18.2 (95% CI: 10.8–25.7) m. mPFS in RAS-mutant and RAS wild-type pts were 7.2 (95% CI: 4.3-10.1) m and 6.7 (95% CI: 2.9-10.6) m, respectively (p = 0.527), with ORRs of 15.8% and 7.7% respectively. mPFS in pts with and without liver metastases were 7.0 m (95% CI: 3.0-11.0) and 7.2 m (95% CI: 6.2-8.2), respectively (p = 0.315), with ORRs of 10.5% and 12.5% respectively. Patients without peritoneal metastases or multiple metastases obtained better mPFS (7.9 m vs. 4.4 m, p = 0.041 ; 7.9 m vs. 3.7 m, p = 0.017), with ORRs of 14.3% vs. 7.1% and 15.8% vs. 6.3%. Treatment-related adverse events (TRAEs) were generally manageable and tolerable. The most common hematological TRAEs (any grade, grades 3-4) included neutropenia (80.0%, 28.6%), leukopenia (68.6%, 22.9%), and anemia (51.4%, 5.7%). Non-hematological TRAEs were mostly grades 1-2, including anorexia (37.1%), fatigue (28.6%) and nausea (14.3%). One case of grade 3 hypertension was reported. No treatment-related deaths were observed. Conclusions: An intermittent Fru+TAS-102 schedule demonstrated encouraging activity with manageable toxicity in refractory mCRC. Clinical trial information: ChiCTR2300078241.

Multimodal immune profile score (IPS) signature as a predictive response biomarker to immune checkpoint inhibitors in tumor mutational burden-high (TMB-H) advanced pancancer cohorts.

e14590 Background: Immune checkpoint inhibitors (ICI) have altered the oncology treatment landscape with improved outcomes. Despite approved predictive biomarkers for ICI such as TMB, refining selection can identify more patients (pts) who may benefit, as most TMB-H pts still fail to achieve response, a critical translational gap. Here we introduce IPS, a validated multimodal DNA-/RNA-based molecular signature, as a predictor of response to ICI. Methods: To establish IPS as a robust predictor of response to ICI, we evaluated its performance in two distinct clinical settings of pancancer pts: a Tempus real-world data (RWD) cohort of TMB-H pts (cohort 1) and metastatic pan-cancer pts from the external AHN Moonshot Biorepository (cohort 2). Cohort 1 consisted of TMB-H advanced solid cancer pts treated with ICI for indications lacking a cancer-specific FDA label. Cohort 2 consisted of metastatic pancancer pts who received ICI therapy on-FDA label. Pts were categorized as IPS-H or IPS-L using a previously validated threshold. In cohort 1, real-world objective response rate (rwORR) was determined by clinician-abstracted longitudinal records, defined as the proportion of pts with documented complete/partial response per physician assessment. In cohort 2, response was assessed according to RECIST v1.1 criteria based on independent radiologic review. ORRs and exact 95% CI are reported in each cohort. Results: Higher response rates were seen in pts with IPS-H status across both cohorts. Among all TMB-H pts (n = 24), higher ORR in IPS-H was seen compared to IPS-L (76% vs. 29%; see table). In TMB-H RWD Cohort 1 (n = 17), 10 tumor types were represented with pancreatic ductal adenocarcinoma as most common. rwORR was 91% (95% CI: 59-100) in IPS-H (n = 10/11), compared to 33% (95% CI: 4-78) in IPS-L (n = 2/6). In observational cohort 2 (n = 17), 6 tumor types were represented; renal cell carcinoma (n = 6) and melanoma (n = 5) were most common. IPS-H pts maintained higher response and disease control rates than IPS-L pts (ORR 33% vs 25%, DCR 67% vs. 50%). Among the subset of TMB-H pts (n = 7), ORR was 50% in IPS-H pts (n = 3/6) and 0% in IPS-L pts (n = 0/1). Conclusions: IPS is a novel multimodal immune response signature that improves precision of prediction of response to ICI compared to TMB. Within the TMB-H population, IPS identifies a subset of pts (IPS-L) that will not respond to ICI therapy. Given regulatory reliance on ORR for accelerated approvals, IPS represents a potentially practice-changing biomarker for refining treatment selection. Additional clinical studies are warranted for prospective validation of IPS. ORR by IPS status among TMB-H Pts. Pt Group (TMB-H only) ORR in IPS-H, % (n/n) ORR in IPS-L, % (n/n) Combined cohort (N=24) 76% (13/17) 29% (2/7) Cohort 1: RWD (N=17) 91% (10/11) 33% (2/6) Cohort 2: Observational (N=7) 50% (3/6) 0% (0/1)

Advancing equity in breast cancer biomarker testing: An updated study on hospital settings and patient involvement.

e13751 Background: Building on previous research, this updated study delves deeper into the persistent disparities in breast cancer biomarker testing across hospital settings. It provides new insights by including emerging biomarkers such as Microsatellite Instability (MSI), HRD, AKT1, PTEN, PIK3CA, PD-L1, NTRK Fusion, and ESR-1. The study also further explores demographic differences and the role of patient/caregiver involvement, aiming to enhance understanding of how these factors influence testing disparities. Methods: Continuing from prior analysis, this updated retrospective study utilizes de-identified physician-reported patient data from the Ipsos Global Oncology Monitor (Dec 2024 - Nov 2025). It involves 434 treating oncologists reporting on patient record data online from 9,775 female BC patients under drug therapy in the US, categorized by treatment setting (urban: 4092, suburban: 4897, rural: 786). This research focuses on updating testing rates, patient demographics (mean age, menopausal status), and patient/caregiver engagement in decision-making by hospital setting. Participating oncologists saw a minimum number of cancer patients per month. Results: This updated analysis reaffirms and expands on prior findings, showing that testing rates for emerging biomarkers remain consistently higher in urban/suburban settings compared to rural settings. Specifically, Microsatellite Instability (MSI) testing was reported in 42% of urban/suburban settings versus 68% in rural settings. Comparably, patterns across other biomarkers like PIK3CA (67% vs. 47%) and NTRK Fusion (51% vs. 37%) were observed. Similar trends were seen when comparing emerging biomarker testing rates by hospital setting for HRD, AKT1, PTEN, PD-L1, and ESR1. Urban/suburban patients were younger (mean age 61.54) compared to rural (mean age 63.03) with a higher percentage of post-menopausal patients in rural areas (95% vs. 89%). In addition, patients/caregivers in urban/suburban settings were more proactive, with 39% researching treatment options or requesting specific treatments, compared to 29% in rural settings. Conclusions: Reinforcing earlier conclusions, this updated study highlights notable, continued disparities in biomarker testing and demographic factors across varied healthcare settings. It emphasizes the urgent need for education and policy reforms that promote equitable access to innovative biomarker tests and personalized treatment strategies. Furthermore, enhancing patient/caregiver involvement in treatment decisions remains crucial for addressing these disparities.

[ ⁶⁸ Ga] Ga-NYM096 PET/CT in patients with primary and metastatic clear cell renal cell carcinoma: A preliminary study.

4537 Background: With limitations of conventional imaging and biopsy, accurate, non-invasive techniques to detect in patients with primary and metastatic clear cell renal cell carcinoma (ccRCC) remain an unmet need. Carbonic anhydrase IX (CAIX) is a tumour antigen highly expressed in ccRCC. NYM096 is a new-generation CAIX targeting small molecule that can be labeled with 68 Ga. It has a higher affinity (almost 100-fold) for CAIX compared to NYM005. This study aims to assess the efficacy of [ 68 Ga]Ga-NY096 PET/ CT to identify ccRCC. Methods: This is an open-label, multicenter study. Patients with primary and metastatic ccRCC were prospectively recruited in the study. A wash-out of 7 days was required if the patients were on tyrosine kinase inhibitors. All patients received an intravenous injection of [ 68 Ga]Ga-NYM096 at a dose of 1-7 mCi and underwent whole body PET/CT scan using a total-body PET/CT scanner at 60 min after injection. They were further divided into two groups: group 1, patients with primary renal mass and group 2, patients with suspected/confirmed metastatic ccRCC, who were scheduled for surgery or biopsy. In some patients, 18 F-FDG PET/CT was also performed within one week before or after [ 68 Ga]Ga-NYM096 PET/CT. The diagnostic efficacy of 68 Ga-NYM096 was compared with that of 18 F-FDG. Results: A total of 24 patients (mean age, 56.7 years±14.4, 18 men) were recruited in this preliminary study. Including 23 patients in group 1 and 1 patient in group 2. All patients had 68 Ga-NYM096 PET/CT, and all patients also had 18 F-FDG PET/CT. The patient-level sensitivity, specificity, and accuracy of [ 68 Ga]Ga-NY096 PET scan was 100%, 90.0%, 95.7% for all patients, and 100%, 90.0%, 95.5% for group 1. One patient in Group 2 was confirmed as a true positive case by histopathological examination. Among patients with positive PET findings, the SUV max of the single most active lesion ranged from 4.9 to 111.8, with a mean (± SD) of 52.2 ± 34.1. This value was significantly higher than the mean SUV max of 5.5 ± 2.9 observed with 18 F-FDG (p < 0.001). The tumor-to- kidney ratio was also higher (3.3 ± 3.0 versus 1.7 ± 3.0, p＜0.05). Conclusions: 68 Ga-NYM096 PET/CT has high diagnostic efficacy for primary ccRCC patients, and its diagnostic efficacy is significantly better than that of 18 F-FDG. It has the potential to become a diagnostic product for both primary and metastatic ccRCC.

Disparities in receipt of guideline-concordant adjuvant chemotherapy and survival outcomes among immigrant patients with colon cancer: Real-world evidence from Ontario.

1639 Background: Immigrants comprise a growing proportion of the Canadian population and may face unique barriers to accessing timely and guideline-concordant cancer care. While the “healthy immigrant effect” suggests that immigrants initially experience better health outcomes, it remains unclear whether this advantage extends to cancer treatment and survival. We studied whether disparities exist in the receipt of adjuvant chemotherapy and survival outcomes among recent immigrant patients with stage III colon cancer in Ontario compared with long-standing Ontario residents. Methods: A population-based real-world retrospective cohort study was conducted using linked administrative health databases housed at the ICES. Adults diagnosed with stage III colon cancer between 2007 and 2020 who underwent surgery within six months of diagnosis were included. Recent immigrants were defined as individuals with a landing date as a resident within ten years before diagnosis, identified using the Immigration, Refugees and Citizenship Canada database; long-standing residents had no recorded immigration date. The primary outcome was receipt of adjuvant chemotherapy within four months of surgery for their cancer. Secondary outcome was all-cause mortality. Results: The cohort included 16,724 patients, of whom 304 were recent immigrants (including 47 refugees). Compared to long-standing residents, recent immigrants were younger, had fewer comorbidities, and were more likely to reside in urban areas. In unadjusted analyses, recent immigrants were more likely to receive adjuvant chemotherapy (RR 1.37; 95% CI 1.23–1.53); however, this association was attenuated in the multivariate analysis (RR 1.08; 95% CI 0.99–1.19). Recent immigrants had significantly lower all-cause mortality, with an adjusted hazard ratio (HR) of 0.70 (95% CI 0.58–0.84). Conclusions: In this large population-based study, recent immigrants with stage III colon cancer in Ontario received comparable guideline-concordant adjuvant chemotherapy and had significantly better overall survival than long-standing residents. These findings suggest that, within a universal healthcare system, recent immigrants may not be disadvantaged in colon cancer treatment and perhaps have better outcomes once engaged in care. Further research is needed to assess whether these findings extend to other cancer types and to non-permanent resident populations.

Levels of VEGF-A, VEGF-C, sVEGFR-1, and sVEGFR-2 in tumor tissue and serum of patients with rare endometrial carcinomas.

e17628 Background: Uterine serous carcinoma (USC) and clear cell carcinoma (CCC) are rare and clinically aggressive forms of endometrial cancer. Under normal conditions, endometrial cells produce angiogenic growth factors to ensure physiological regeneration of the uterine mucosa. Vasculogenic mimicry—a process mediated by the VEGF-A/sVEGFR-1 signaling pathway and independent of sVEGFR-2 activation—may play a role in the pathogenesis of these rare endometrial carcinomas. The objective of this study was to evaluate the levels of vascular endothelial growth factors (VEGFs) and their soluble receptors (sVEGFRs) in tumor tissue and peripheral blood of patients with USC and CCC. Methods: Levels of VEGF-A, VEGF-C, sVEGFR-1, and sVEGFR-2 in tumor tissue and serum were determined by enzyme-linked immunosorbent assay (ELISA) in 21 patients with grade 3 USC and 20 patients with CCC. A comparison group consisted of 20 patients with grade 3 endometrioid carcinoma (EC). Reference values were obtained from intact endometrium samples of 20 women undergoing surgery for uterine fibroids (tissue controls) and blood samples from 20 women without oncological diseases (serum controls). The mean age of participants was 55 ± 7.8 years. All participants provided written informed consent. Statistical analysis was performed using parametric and nonparametric tests with adjustments for multiple comparisons. Results: Regardless of the histological subtype, VEGF-A levels in tumor tissue were two-fold higher than in intact endometrium. VEGF-C levels in USC and CCC tumors were 3.2-fold higher than reference values and 80% higher than in EC tumors. The concentration of sVEGFR-2 was significantly reduced in the tissue of rare carcinomas (on average 1.6-fold compared to reference values), while no differences were found in EC tumors. sVEGFR-1 levels in tumor tissue from USC and CCC patients were 3- to 4.8-fold higher than in EC and 4.3- to 6.7-fold higher than reference values. In serum, VEGF-A levels in patients with USC and CCC were 1.7- and 3.1-fold higher, respectively, compared to the EC group, and 3.8- to 12-fold higher than reference values. Serum sVEGFR-1 levels were also elevated, exceeding reference values by 1.4- to 6.7-fold. Serum VEGF-C levels were, on average, 1.6-fold higher than reference values in all examined patients. The concentration of sVEGFR-2 in the blood did not differ from control values in any group. Conclusions: The significant increase in sVEGFR-1 levels coupled with the decrease in sVEGFR-2 levels in USC and CCC tumor tissue suggests the possible activation of vasculogenic mimicry. This mechanism may contribute to the high aggressiveness of these tumors and explain their limited sensitivity to antiangiogenic therapy targeting the classical VEGF/VEGFR-2 pathway.

Telisotuzumab adizutecan (Temab-A) plus osimertinib (osi) as 1L treatment for unresectable/metastatic NSCLC.

TPS8663 Background: Most patients (pts) with EGFR-mutated (Mut) NSCLC and 1L osi treatment will eventually develop resistance. Although 1L combination strategies (osi+chemo or amivantamab+lazertinib) show potential long-term benefits, associated toxicities can impact quality of life. Temab-A, an antibody-drug conjugate with a topoisomerase 1 inhibitor payload, targets c-Met protein. MET gene amplification and c-Met protein expression are associated with poor survival outcomes in NSCLC. A Ph1 study of Temab-A in pts with refractory EGFR Mut NSCLC reported encouraging activity and a manageable safety profile (NCT05029882). Herein, we describe a Ph2/3 study of Temab-A+osi as 1L in pts with previously untreated, locally advanced or metastatic NSCLC harboring common EGFR Mut. Methods: Planned enrollment is ~194 pts in Ph2 and ~500 in Ph3 across ~200 sites in 22 countries. Adults (≥18 years) must have histologically/cytologically confirmed metastatic/locally advanced nonsquamous NSCLC with documented EGFR Mut and measurable disease by RECISTv1.1. Pts with prior EGFR tyrosine kinase inhibitor treatment in the metastatic setting are excluded. During dose escalation (Ph2), pts will receive Temab-A (1.6 or 2.4mg/kg) every 3 weeks (Q3W, 1 cycle) intravenously (IV) + 80mg osi daily. During dose expansion (Ph2), after 1 cycle of osi, pts will be randomized to receive Temab-A (1.6, 2.0, or 2.4mg/kg) Q3W IV + 80mg osi daily, or osi monotherapy, and stratified based on c-Met expression levels and history of CNS involvement. Ph2 primary objectives are safety/tolerability, efficacy as measured by objective response rate of Temab-A+osi, and determination of the recommended Ph3 dose (RP3D). Ph2 primary efficacy endpoint is objective response based on blinded independent central review assessment per RECIST v1.1. In Ph3, randomized pts will receive Temab-A+osi at RP3D or standard of care. Additional details for Ph3 will be confirmed after completion of Ph2. Clinical trial information: NCT05029882 .

First-in-human phase 1 evaluation of the world’s first tri-specific SIRPα–PD-1–TGF-β Fc fusion protein HCB301 in advanced solid tumors.

e14570 Background: Tumor immune resistance arises from coordinated suppression of innate immunity, adaptive T-cell activity, and stromal immune exclusion. HCB301 is a world-first tri-specific Fc fusion protein rationally engineered to simultaneously block macrophage inhibition (SIRPα), relieve T-cell exhaustion (PD-1/PD-L1), and neutralize TGFβ–mediated immune exclusion through a mutant TGFβRII-based TGFβ trap. Preclinical studies confirmed concurrent activation across all three pathways, including innate and adaptive immune responses, while preserving hematologic safety. This first-in-human study evaluates the safety, tolerability, pharmacokinetics, and preliminary biological and antitumor activity of HCB301. Methods: HCB301-101 (NCT06487624) is an ongoing, open-label, multicenter, Phase 1 dose-escalation study using an adaptive BOIN-guided design to evaluate 7 predefined weekly HCB301 dose levels in patients with advanced solid tumors or relapsed/refractory classical Hodgkin lymphoma. Primary endpoints include safety, dose-limiting toxicities, and determination of maximum tolerated dose. Secondary endpoints include pharmacokinetics and immunogenicity. Exploratory endpoints include cytokine profiling, peripheral immune-cell phenotyping, circulating tumor DNA, and preliminary antitumor activity assessed by RECIST v1.1. Safety is assessed per CTCAE v5.0. Results: Across the initial dose levels evaluated, HCB301 demonstrated linear pharmacokinetics and a half-life of ~2.5 days. Treatment-related adverse events were consistent with immune activation and included transient hypoxemia, hypertension, and cytokine-associated symptoms, predominantly Grade 1–2 and manageable with protocol-specified monitoring. No unexpected immune-mediated, hematologic, or TGF-β–related toxicities were observed. Early pharmacodynamic analyses showed modulation of immune-associated biomarkers consistent with multi-specific target engagement across innate, adaptive, and stromal immune pathways. Preliminary signals of antitumor activity were observed in heavily pretreated patients. Conclusions: These first-in-human data establish the clinical feasibility of tri-specific Fc fusion immunotherapy, validating simultaneous targeting of innate, adaptive, and stromal immune resistance mechanisms within a single molecule. The favorable early safety profile, predictable pharmacokinetics, and initial biological and antitumor signals support continued dose escalation and cohort expansion of HCB301. Clinical trial information: NCT06487624 .

Decoupling of hygromechanical stimuli without cross-interference enabled by distinct ion-electron charge transport

Molecular grouping of NUT carcinoma within a cancer family context.

e18053 Background: NUT carcinomas are characterized by ectopic expression of nuclear protein in testis (NUT). These rare squamous cell carcinomas carry a poor prognosis despite chemotherapy. Since new extensive molecular profiling has shown that cancers with different histologies can converge on common oncogenic pathways, rare cancers like NUT carcinoma have been increasingly grouped into "molecular families" based on shared molecular circuitry. We sought to group NUT carcinoma within the context of a cancer family. Methods: Proteins in the NUT interactome were identified using BioGRID, a database of protein, genetic, and chemical interactions. The identified corresponding genes were used to obtain sample data from 5 cancer subtypes in cBioPortal, a resource for exploration of multidimensional cancer genomics data sets. Mutational, copy number variations, mRNA, protein, and structural variant data identified by cBioPortal were grouped into a sample by gene matrix. The Multi-Dendrix Chain Monte Carlo (MCMC) algorithm, which identifies driver pathways from patterns of mutual exclusivity between mutations, was run on the matrix to identify driver pathways across a range of pathway sizes (3-5) and number of pathways (2-3); a permutation test with 100 simulations was used to assess for statistical significance (p< 0.05). We tested the coverage of the identified pathways by counting the number of samples of each cancer with at least one mutation in a gene implicated in an identified pathway. Results: We identified 56 unique human proteins in the NUT interactome using BioGRID. We searched Head and Neck Squamous Cell Cancer (H&N), Cutaneous Squamous Cell Cancer (CSCC), Ewing Sarcoma, Osteosarcoma, and Pancreatic Acinar Cell Carcinoma (pACC) datasets in CBioPortal. Ewing Sarcoma and CSCC had pathways identified by MCMC that reached statistical significance across the range of pathway sizes. Osteosarcoma had the highest coverage (75.76%) and Ewing Sarcoma had the lowest coverage (4.85%) of pathway mutations in samples. We were unable to run the permutation test on the H&N dataset and excluded it from our subsequent analyzes. Conclusions: The results of our study provides some evidence of subsets of cancers with a shared oncogenic pathways with NUT carcinoma; further work is needed to better characterize these relationships. Cancer # Genes Significant Sets (pathway size, # pathways, # sets) # Samples Sample Coverage Ewing Sarcoma 17 (3,2,25), (3,3,25), (4,2,21), (4,3,25), (5,2,2), (5,3,17) 495 7, 4.85% CSCC 53 3,2,25), (3,3,25), (4,2,25), (4,3,25), (5,2,10), (5,3,25) 151 104, 68.87% Osteosarcoma 52 (3,2,25), (3,3,25), (4,2,3), (4,3,20), (5,3,1) 66 50, 75.76% pACC 13 (3,2,1), (3,3,1) 69 12, 17.39%

Patient-reported outcomes based on voice-based artificial intelligence (VAAIPRO): A fast and innovative QOL data collection application.

e13658 Background: Health-related quality of life (QoL) is a key endpoint in oncology, typically assessed using validated paper or electronic questionnaires. Data collection faces major methodological and logistical challenges, including declining patient adherence, reporting burden, barriers to electronic PROs, staff workload, adherence to assessment schedules and data reformatting. As a result, QoL outcomes are often unavailable in the primary analysis. Therefore, we evaluated the feasibility of a mobile phone–based, artificial intelligence–driven patient-reported outcome (PRO) application that directly captures data in an executable format, automates assessment scheduling, and minimizes human intervention in data acquisition and processing. Methods: Health-related QoL instruments (EORTC QLQ-C30 and EQ-5D/EuroQol-5D) were simulated as voice-based questionnaires using a dedicated software application. Each participant first received a written questionnaire with instructions and then called a designated telephone number. An AI-driven voice agent conducted an automated interview, reading the items aloud and prompting numerical responses. The agent used an Automatic Speech Recognition system trained for multi-accent speech optimized for North Indian dialects. It analyses the voice signal in real time to detect fatigue or exhaustion and automatically logs all responses into structured Excel spreadsheets. Analysing exhaustion in voice, the agent was capable of rescheduling a follow-up call at the patient’s convenience, preserving the executed questionnaire context across interruptions. It also controlled the timing and frequency of longitudinal data collection by automatically initiating outbound calls at pre-specified dates and times. Results: The EORTC questionnaire was administered to 50 patients. The average time spent on completion was.12 minutes. On the first attempt, only 25/50 completely answered the questionnaire, 10 answered only a part, and 15 did not answer at all. A second attempt to continue questionnaire in patients who interrupted answering, was unsuccessful. At the four week follow up, only 11/25 (44%) completed the questionnaire. The most common reason for not answering was no call pick-up. A shorter Euro-QL was administered to 40 patients with an average completion time of 2.5 minutes. In this series 37 / 40 (96%) responded completely. The reason for not answering was non-mobile connectivity. Conclusions: Voice-assisted, AI-based PRO assessment is a novel approach that enables efficient, user-friendly, and timely data collection while reducing the need for human resources. The questionnaire length may hinder completion; however, this can be mitigated with better patient counselling and user support. If widely adopted and rigorously validated, VAAIPRO could substantially transform QoL data capture and reporting.

Genetic testing uptake through an enhanced oncology nurse–led intervention in patients with solid tumors (GENESIS): A pilot study.

TPS1677 Background: Identification of pathogenic germline variants (PGV) in patients with solid tumors is critical for directing targeted therapies, surveillance, and cascade testing for family members. Despite established National Comprehensive Cancer Network (NCCN) guidelines, uptake of genetic counseling and testing (GCT) remains suboptimal, with recent data suggesting <7% utilization in some cancer populations. Barriers are pronounced in community oncology settings due to limited access to genetic counselors and reliance on physician-initiated referrals. Oncology nurses routinely provide education during systemic therapy initiation, presenting a unique, underutilized touchpoint to bridge this gap. The GENESIS study (NCT06436157) evaluates the feasibility and impact of a novel, nurse-led "enhanced education" intervention on GCT uptake. Methods: This is a single-center, prospective, randomized (1:1) pilot trial conducted at a community cancer center. Eligible participants are adults (≥18 years) with solid tumors (breast, ovarian, prostate, pancreatic, colorectal, and others per NCCN guidelines) who are starting or switching systemic therapy, meet NCCN criteria for GCT, and have no prior germline testing. The study plans to accrue 60 patients. Participants are randomized to the Usual Care arm (standard therapy education; clinician-initiated referral) or the Enhanced Education Intervention arm. In the intervention arm, trained oncology nurses integrate a specific GCT educational module into the standard chemotherapy teaching session. For eligible/agreeable patients, the nurse directly places the GCT referral order and executes a follow-up "nudge" to referral coordinators within one week. The primary endpoint is the percentage of patients proceeding to GCT consultation. Secondary endpoints include GCT referral rates, time from order to consultation, time to testing completion, and implementation feasibility assessed via the Acceptability of Intervention Measure (AIM) and retention rates. Clinical trial information: NCT06436157 .

Application of Bayesian methodology in radiopharmaceutical therapies dose optimization.

e15152 Background: Radiopharmaceutical therapies (RPTs) exhibit complex dose-response relationships due to inter-patient heterogeneity in tumor uptake, dosimetry, and radiation exposure. Recent FDA guidance on RPT dose optimization highlights the importance of randomized dose optimization, encourages modeling and simulation, and supports dose-response evaluation with an overall benefit-risk focus. Bayesian trial designs enable adaptive decision-making, incorporate uncertainty, and integrate historical and external data. These approaches are discussed in recent FDA guidance on Bayesian methodology and are increasingly used in oncology dose optimization, making them particularly well suited for RPT development. Methods: We applied Bayesian methods across early and late-phase oncology development: Bayesian Optimal Interval for Phase I/II Trial Design (BOIN12) was evaluated to inform dose-escalation decisions by jointly incorporating safety and preliminary efficacy information. Bayesian continuous efficacy monitoring using posterior and predictive probabilities was implemented in dose expansion or seamless phase II/III trials (NCT06726161, NCT06590857, NCT05595460, NCT07165132). Bayesian response-adaptive randomization (RAR) was assessed in phase II or III RPT dose-optimization trials, in which multiple dose regimens were initially equally randomized, with interim adaptation based on emerging efficacy and toxicity. Operating characteristics were characterized via simulations under clinically relevant dose-efficacy and dose-toxicity scenarios representative of RPT programs. Results: Simulations demonstrated that Bayesian designs reduced sample size and trial duration while enabling efficient adaptive decision-making. For phase I dose escalation, BOIN12 designs showed a higher probability of selecting doses with acceptable safety profiles compared with traditional rule-based approaches. For dose-expansion and seamless phase II/III settings, Bayesian continuous monitoring supported timely interim decision-making while preserving operating characteristics. For phase II or III dose-optimization trials, Bayesian RAR enriched enrollment to regimens with superior therapeutic indices and preserved type I error and power under clinically meaningful dose-response scenarios. Conclusions: Bayesian trial designs, including model-based dose escalation, continuous monitoring, and RAR, provide a rigorous and FDA-aligned framework consistent with recent FDA guidance on dose optimization in RPT development and Bayesian methodology. Simulation and modeling play a critical role in evaluating operating characteristics, informing design choices, and supporting dose selection under clinically relevant scenarios. These methods enhance ethical efficiency, benefit-risk characterization, and evidence-based dose optimization.

Epidemiology of early-onset colorectal cancer in the WHO Eastern Mediterranean Region: Regional and global comparisons.

3660 Background: Early onset colorectal cancer (EO-CRC) is increasing globally, yet studies from the WHO Eastern Mediterranean Region (EMRO) are limited. We quantified the burden, temporal trends, and future projections of EO-CRC in EMRO and compared patterns with regional and global estimates. Methods: We conducted a population based study using GLOBOCAN 2022 data. EO-CRC outcomes included age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and 1-, 3-, and 5-year prevalence per 100000 population. Age-specific analyses were conducted. Temporal trends were assessed using Estimated Annual Percentage Change (EAPC). Associations between Human Development Index (HDI) and EO-CRC outcomes were evaluated using Pearson correlation coefficients (r). Results: In 2022, EMRO recorded 53941 new CRC cases (ASIR = 8.9), including 15381 EO-CRC cases (ASIR = 2.5), and 29918 CRC deaths (ASMR = 5.1), including 6965 EO-CRC deaths (ASMR = 1.1). EO-CRC incidence was lowest among individuals aged 0–19 years (ASIR = 0.17), increased in those aged 20–34 years (ASIR = 1.9), and peaked among adults aged 35–49 years (ASIR = 8.4), who accounted for most EO-CRC cases and deaths. Marked inter-country heterogeneity was observed. Jordan had the highest EO-CRC incidence (ASIR = 4.2), followed by Libya (ASIR = 3.5) and Iran (ASIR = 3.3), while EO-CRC mortality was highest in Jordan (ASMR = 1.9), followed by Oman and Somalia (ASMR = 1.8 each). Five-year EO-CRC prevalence was highest in Saudi Arabia (14.7 per 100,000), Oman (13.5), and Iran (13.3), but remained below 3 per 100000 in Afghanistan and Somalia. Males exhibited higher EO-CRC incidence (ASIR = 2.6) and mortality (ASMR = 1.2) than females (ASIR = 2.4; ASMR = 1.1), although several countries demonstrated a higher female burden. Compared with other WHO regions, EMRO demonstrated one of the highest EO-CRC mortality rates globally (ASMR = 1.1), exceeding Europe (ASMR = 1.0), South-East Asia (ASMR = 0.68), and the Western Pacific (ASMR = 0.98), despite having lower overall CRC incidence. Temporal trend analyses revealed concerning increases in EO-CRC incidence, with significant rises in Israel (EAPC = +2.58%). EO-CRC mortality was inversely correlated with HDI (r = −0.45; p = 0.034), indicating a disproportionate mortality burden in lower HDI countries. Projections indicate that annual EO-CRC cases will increase from 15381 in 2022 to 24396 by 2050, and annual deaths from 6965 to 11005, underscoring a rapidly escalating regional burden. Incidence and mortality are projected to rise faster in females across EMRO by 2050. Conclusions: EO-CRC is a rapidly growing, inequitable burden in EMRO, with high mortality and marked inter-country differences. Its disproportionate impact on lower HDI countries and younger populations highlights the urgent need for targeted interventions, including early detection and awareness campaigns.