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Phase 1A/B study of AB248, a CD8+ selective IL-2 mutein fusion protein, alone or in combination with pembrolizumab, in patients with advanced solid tumor malignancies.

2616 Background: High-dose IL-2 demonstrates modest activity in melanoma and RCC but its use is limited by severe toxicity. AB248 is a novel IL-2 fusion protein of an attenuated IL-2 mutein linked to an antibody targeting CD8β that features >500-fold selectivity for CD8+ T cells and shows strong anti-tumor activity both alone and with anti-PD1 in preclinical models. In addition to CD8+ T cell expansion and activation, the drug avoids NK cell toxicity and Treg-mediated immunosuppression. Methods: NCT05653882 is a phase 1A/B study investigating the safety, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of AB248 alone or with pembrolizumab in locally advanced/metastatic solid tumor malignancies, including melanoma, having previously progressed through PD-1/PD-L1 checkpoint blockade. The study’s primary objective was to assess the safety and tolerability of AB248 alone and in combination with pembrolizumab. Results: As of December 1, 2025, 61 patients (pts.) were treated with monotherapy (MT) at 6 dose levels across 3 schedules (Q2W at 0.02mg/kg-0.75mg/kg; QW at 0.15mg/kg; Q3W at 0.3mg/kg). 68 additional pts. were treated with combo therapy (CT) at Q3W 0.15-0.3mg/kg and step-up dosing. The most common TEAEs (> 95% G1-2) among all pts. were fatigue (50%), rash (49%), nausea (43%), chills (33%), pyrexia (32%), vomiting (32%) and diarrhea (30%). Maximum tolerated doses (MTDs) were 0.5 mg/kg for MT Q2W and 0.15 mg/kg for CT Q3W. An MTD was not reached for CT step-up dosing. 41 cutaneous (cut) and mucosal (muc ) melanoma pts. were evaluable for response across MT and CT dose cohorts, with 95% of pts. having received prior IO doublet therapy (anti-PD1 + anti-CTLA or anti-LAG3) and 83% having received ≥ 2 anti-PD1 regimens. Among evaluable cut melanoma pts., 2 confirmed PRs (18%) were observed among 11 pts. enrolled at higher MT dose levels (net tumor reductions of 78.8% and 87.2%) and 2 confirmed PRs (12%) were observed among 16 CT pts. (37.5% and 57.5%). Among 11 muc melanoma pts., 3 confirmed PRs (27%) were observed in CT dosing. One additional muc melanoma pt. received 0.5 mg/kg MT and remained on study with SD > 15 mos. AB248 exhibited dose-proportional PK that is comparable between MT and CT dosing. Peripheral PD data demonstrated robust and preferential CD8+ T cell expansion, with >20X expansion in MT (0.3 mg/kg and above) and >11X expansion in CT dosing (0.15 mg/kg and above). Further data on safety, PK, PD, and preliminary anti-tumor activity will be presented. Conclusions: AB248 demonstrates robust anti-tumor activity across heavily IO-pretreated patients with metastatic melanoma (incl. mucosal melanoma). Combined with an acceptable safety profile, favorable PK and differentiated PD, the drug’s anti-cancer activity merits further investigation. Clinical trial information: NCT05653882 .

A non-invasive methylation-based NGS assay for sensitive detection of pancreatic cancer.

e16452 Background: Non-invasive tools with high sensitivity to distinguish pancreatic cancer from benign pancreatic lesions are limited. Cell-free DNA (cfDNA) offers promise for early detection but is constrained by low DNA input and separated workflows. We developed SPIRAL (Single-Portion Input Resourceful Assay for Liquid Biopsy), which enables simultaneous genomic and epigenetic library construction from a single cfDNA sample. We evaluated a methylation-based assay using SPIRAL platform in patients with pancreatic lesions. Methods: In the prospective DAYBREAK Study (NCT05495685), peripheral blood samples were collected from patients with pancreatic cancer (n = 67) and benign pancreatic lesions (n = 31). cfDNA methylation was analyzed using the STELLA algorithm. Sensitivity and specificity were assessed overall and by disease stage and histology. Results: Overall sensitivity was 70% (48/67) with a specificity of 87% (27/31). Sensitivity increased by stage: 63% in stage I (12/19), 70% in stage II (23/33), 80% in stage III (8/10), and 100% in stage IV (5/5). Sensitivity was 79% (41/52) for pancreatic ductal adenocarcinoma and 30% (3/10) for pancreatic neuroendocrine tumors. Conclusions: A methylation-based cfDNA assay using the SPIRAL platform distinguishes malignant from benign pancreatic lesions. Ongoing studies integrating mutation and methylation features and expanding sample size may improve the performance. Clinical trial information: NCT05495685 .

Phase II study of bevacizumab plus trifluridine/tipiracil and irinotecan as second-line therapy for RAS wild-type metastatic colorectal cancer.

e15578 Background: Patients with RAS wild-type (RASwt) metastatic colorectal cancer (mCRC) progressing on first-line fluoropyrimidine-based chemotherapy plus anti-EGFR therapy have limited and often suboptimal second-line treatment options. Trifluridine/tipiracil (TAS-102) is an oral cytotoxic agent that inhibits tumor growth through incorporation into DNA and disruption of DNA function, potentially overcoming fluoropyrimidine resistance. We conducted a phase II study to evaluate the efficacy and safety of bevacizumab combined with TAS-102 and irinotecan in this setting. Methods: In this single-arm phase II trial (ChiCTR2100046678), patients with RASwt mCRC who progressed after first-line anti-EGFR therapy plus chemotherapy received TAS-102 (35 mg/m², days 1–5), bevacizumab (5 mg/kg), and irinotecan (180 mg/m²) every 2 weeks. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From August 2021 to January 2026, 27 patients were enrolled. The median age was 59 years (range, 42-75), male accounted for 81.5%,Most patients (26/27) had an ECOG status of 1. As of data cutoff (January 2026), 24 patients had ≥1 postbaseline tumor assessment; 7 remained on treatment. Best overall responses included partial response in 5 patients (20.8%), stable disease in 18 (75.0%), and progressive disease in 1 (4.2%). The confirmed ORR was 20.8% (95% CI: 3.3–38.4%) and DCR was 95.8% (95% CI: 87.2–100.0%). With a median followup of [X] months, median PFS was 7.7 months (95% CI: 4.99–10.41) and median OS was 20.7 months (95% CI: 8.83–31.31). Grade ≥3 treatmentrelated adverse events (occurring in ≥5% of patients) were neutropenia (40%), leukopenia (24%), anemia (8%), and thrombocytopenia (8%). No treatmentrelated deaths were reported. Conclusions: The combination of bevacizumab, TAS-102, and irinotecan showed promising clinical activity and manageable toxicity as secondline therapy for RASwt mCRC patients who progressed on prior anti-EGFR-based treatment. These results support further evaluation of this regimen in randomized controlled trials. Clinical trial information: ChiCTR2100046678.

Effects of external beam radiation therapy and androgen deprivation therapy on physical activity of men with non-metastatic prostate cancer.

e17028 Background: Physical activity (PA) has been shown to have a profound positive impact on the quality of life of people living with cancer and cancer survivors. However, there has been little research on the changes in PA for patients with prostate cancer despite its high prevalence. External beam radiation therapy (EBRT) and androgen deprivation therapy are standard treatments for non-metastatic prostate cancer (NMPC), although they are accompanied by side effects such as fatigue. Understanding these effects is crucial for identifying interventions to mitigate the consequences of NMPC and its associated treatments. Therefore, this natural history aimed to evaluate how EBRT and ADT influence free-living PA in men with NMPC. Methods: PA data was measured from 68 NMPC patients undergoing EBRT (51 with ADT, 17 without). Participants wore Actical devices around the waist continuously for four days during three assessment points: before EBRT (Time 1), mid-EBRT (Time 2: days 16–22), and end of EBRT (Time 3: days 38–44). PA metrics included Total Activity Counts (TAC), Inactive Time (< 100 counts/min), Light-Intensity Physical Activity (LIPA; ≥100 counts/min; < 1535 counts/min), and Moderate-to-Vigorous Physical Activity (MVPA; ≥1535 counts/min). Results: For men receiving EBRT alone, mean TAC decreased by 1.97%, from 98,791 in time 1 to 96,839 in time 3. Mean IT decreased by 3.16%, from 622.63 minutes in time 1 to 602.93 minutes in time 3. Mean LIPA increased by 11.83% over the same period, from 91.72 minutes to 102.58 minutes. Mean MVPA minutes decreased by 1.41%, from 36.95 minutes in time 1 to 36.43 minutes in time 3. For men receiving EBRT in conjunction with ADT, mean TAC decreased by 16.13%, from 80,534 in time 1 to 67,543 in time 3. Mean IT increased by 3.11%, from 601.13 minutes in time 1 to 619.85 minutes in time 3. Mean LIPA decreased slightly by 0.19%, from 80.34 minutes in time 1 to 80.19 minutes in time 3. Mean MVPA minutes decreased by 20.14%, from 23.34 minutes in time 1 to 18.63 minutes in time 3. ANCOVA revealed significant differences for LIPA (p = 0.024), TAC (p = 0.037), and MVPA (p = 0.0065) when comparing between the ADT (ADT+) and no ADT (ADT-) groups at time 3. Conclusions: Our results showed variability in PA levels among men receiving EBRT alone, with some even increasing their PA levels across treatment. However, men who received EBRT+ADT had significantly less PA than those who received EBRT alone by the end of treatment. This is consistent with previous reports that concomitant use of ADT presents a substantial barrier to maintaining PA levels. We further identify that these consequences are most significant at the end of EBRT treatment. Understanding these treatment specific effects is critically important to identify when patients are most vulnerable, informing interventions aimed at preserving PA through early rehabilitative services.

Efficacy and safety of cetuximab-irinotecan rechallenge versus regorafenib in <i>RAS</i> wild-type metastatic colorectal cancer.

3537 Background: Anti-epidermal growth factor receptor (EGFR) antibodies are widely used in the treatment of RAS wild-type metastatic colorectal cancer (mCRC) across various lines of therapy, including after disease progression. Methods: A single-center, prospective, randomized controlled trial (ChiCTR1900026961) evaluated the efficacy of cetuximab rechallenge in mCRC patients with RAS wild-type tumors who had initially responded to cetuximab-based therapy but subsequently progressed on a cetuximab-free regimen. The trial compared cetuximab plus irinotecan with regorafenib, with progression-free survival (PFS) as the primary endpoint and overall survival (OS), disease control rate (DCR), objective response rate (ORR), and safety as secondary endpoints. Results: Among 68 patients with microsatellite-stable (MSS), RAS wild-type tumors, 35 received cetuximab rechallenge therapy and 33 received regorafenib. The cetuximab group achieved a DCR of 68.6% and an ORR of 8.6%, both significantly higher than those observed in the regorafenib group. Median PFS was 5.5 months in the rechallenge group compared with 2.6 months in the regorafenib group, while median OS was 18.8 months versus 10.4 months, respectively. Adverse events in the cetuximab group were predominantly grade 1–2 and manageable with supportive care. Univariate and multivariate Cox regression analyses identified age, ECOG performance status, and washout period duration as independent prognostic factors. A nomogram was developed to predict the efficacy of cetuximab rechallenge therapy. Conclusions: These findings suggest that cetuximab rechallenge offers promising clinical activity with acceptable toxicity in RAS/BRAF wild-type mCRC, supporting further investigation of rechallenge strategies and biomarker-guided approaches to optimize outcomes in advanced CRC. Clinical trial information: ChiCTR1900026961.

A phase 1/2a, multicenter, first-in-human, open-label clinical trial evaluating MDX2004 monotherapy in patients with advanced tumors.

TPS2686 Background: MDX2004 is a trispecific antibody–fusion protein developed as an immunotherapy for advanced cancers. It is designed to stimulate T cells through engagement of CD3, CD28, and 4-1BB, thereby enhancing immune activation. MDX2004 is expected to promote activation and expansion of T lymphocytes, including stem and memory T-cell populations. Methods: This Phase 1/2, multicenter, first-in-human, open-label clinical trial evaluates MDX2004 in patients with advanced or metastatic solid tumors (NCT07110584). The study includes a Phase 1a dose-escalation stage guided by a Bayesian Optimal Interval (BOIN) design targeting a maximum tolerated dose toxicity rate of 30%; a Phase 1b indication-optimization stage in up to five tumor types; a Phase 1c dose-optimization stage in up to three indications; and a Phase 1d/2a expansion at the recommended Phase 2 dose (RP2D) in a single indication. In Phase 1a, patients with advanced solid tumors receive escalating intravenous doses of MDX2004. Phase 1b evaluates a selected dose in patients with homogeneous indications to assess preliminary efficacy. In Phase 1c, patients with selected indications are randomized 1:1 to two dose cohorts using a Bayesian Optimal Phase 2 (BOP2) design. Once the RP2D is established, Phase 1d/2a will enroll approximately 30 patients into a single cohort using a BOP2 design. The primary objectives across study phases are to characterize the safety, tolerability, and antitumor activity of MDX2004. Secondary endpoints include time to response, disease control rate, duration of response, pharmacokinetics, and immunogenicity. Radiologic tumor assessments are performed every 8 weeks, and treatment continues until disease progression per RECIST v1.1 (investigator assessed), unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion. The study is planned to be conducted in Australia, Israel, Moldova; patient recruitment is ongoing. Clinical trial information: NCT07110584 .

The weight of each node: Modeling and quantifying breast cancer lymphedema risk.

e12750 Background: Lymphedema (LE) is a common morbidity following breast cancer surgery, affecting quality of life. While axillary surgery is a LE risk factor, prior studies have largely stratified risk by surgical procedure, resulting in wide-ranging risk estimates. Although procedure type likely contributes, data quantifying per-lymph node (LN) risk and other factors remain limited. This study was performed to identify risk factors for LE development, quantify the incremental risk per LN removed, and provide quantitative estimates not previously established. Methods: A cohort study identified from institutional medical records was performed of patients with nonmetastatic noninflammatory invasive breast cancer having axillary surgery at an NCI-designated comprehensive cancer center from 2013–2022. Axillary surgery was categorized as sentinel lymph node biopsy alone (SLNB), delayed completion axillary dissection after prior SLNB (dALND), or upfront axillary dissection with or without SLNB performed at the same procedure (ALND). Multivariable logistic regression with LASSO-based variable selection was used to identify independent predictors of LE using the training set, with validation in a held-out test set. Final model parameters were estimated using the full cohort. Results: A total of 3,969 patients were included, whose mean age was 59.6 ± 12.1 years. BMI averaged 30.0 ± 7.0 and mean follow-up was 5.0 ± 2.8 years. A mean of 4.4 ± 5.1 LNs was removed and LE occurred in 14.0% overall. SLNB was performed in 78.9%, dALND in 1.5%, and ALND in 19.6%. Independent predictors of arm LE included increasing number of regional LN removed (OR 1.06 per node, p = 0.046), higher BMI (OR 1.04 per kg/m², p &lt; 0.001), younger age (OR 0.98 per year, p &lt; 0.001), radiotherapy (OR 1.79, p &lt; 0.001), and mastectomy without reconstruction (OR 2.40 vs lumpectomy, p &lt; 0.001). Model-predicted risk rose as greater numbers of LNs were excised, rising to 29.9% when ≥24 LN were removed. The risk-prediction model demonstrated good discrimination (AUC = 0.73) and calibration (slope = 0.95). Conclusions: The increase in risks of LE conferred by each LN removed and other factors such as higher BMI, younger age, radiotherapy, and mastectomy are now estimable. With these contributors now quantified, physicians have better estimates than prior procedure-based ranges. Such data may better guide preoperative counseling, postoperative surveillance, and direct more tailored interventions for those at greatest risk.

Income inequality and cervical cancer: A comparative analysis of demographics and healthcare burden of women in the lowest and highest income quartiles.

5521 Background: Cervical cancer disproportionately affects women of lower socioeconomic status, yet comprehensive data comparing the demographic profiles and comorbidity burden across income strata remain limited. This study examines differences in patient characteristics, comorbidities, and healthcare utilization between women in the lowest and highest income quartiles hospitalized with cervical cancer in the United States. Methods: We identified women hospitalized with cervical cancer in the United States between 2016 and 2022 using ICD-10 codes C53.x in the National Inpatient Sample. Patients were classified into the lowest (0–25th percentile) and highest (76th–100th percentile) income quartiles based on median household income for their residential ZIP code. We compared demographic characteristics including age, race, socioeconomic distribution, and clinically relevant comorbidities across the two groups. Healthcare utilization was evaluated by analyzing length of stay and inflation-adjusted mean hospital charges. Results: We identified 88,240 women hospitalized with cervical cancer; 69.7% were in the lowest income quartile and 30.3% in the highest. Women in the highest income quartile were older (mean age 55.45 vs. 52.62 years, p&lt;0.001) and incurred higher inflation-adjusted hospital charges ($88,955 vs. $76,121, p&lt;0.001), though length of stay was comparable (5.64 vs. 5.82 days, p=0.134). Significant racial disparities were evident: the highest income quartile had more White patients (63.2% vs. 46.2%) while the lowest quartile had more Black (29.1% vs. 11.1%) and Hispanic (19.0% vs. 12.2%) patients (p&lt;0.001). Women in the lowest income quartile had significantly higher prevalence of smoking (40.2% vs. 31.0%), diabetes (19.8% vs. 13.8%), chronic kidney disease (16.6% vs. 14.0%), obesity (14.4% vs. 11.5%), HIV (2.1% vs. 0.9%), depression (12.1% vs. 10.9%), opioid use disorder (3.1% vs. 1.9%), drug abuse (7.7% vs. 3.5%), and alcohol abuse (2.0% vs. 1.4%) (all p&lt;0.05). Conversely, the highest income quartile had higher rates of metastatic cancer (41.8% vs. 38.7%, p&lt;0.001). No significant differences were observed in dyslipidemia (17.6% vs. 16.7%, p=0.165), cachexia (4.3% vs. 4.6%, p=0.396), or palliative care utilization (13.0% vs. 13.5%, p=0.413). Conclusions: Women in the lowest income quartile comprise the majority of cervical cancer hospitalizations and face disproportionately higher rates of modifiable risk factors and comorbidities. Targeted interventions addressing screening access, preventive care, and comorbidity management in low-income populations are essential to reduce health disparities in cervical cancer.

A phase 2 trial of IO102-IO103 and nivolumab-relatlimab in previously untreated, unresectable melanoma.

9519 Background: IO102-IO103 is an investigational cancer vaccine that targets both tumor and immune-suppressive cells in the tumor microenvironment. IO102-IO103 has demonstrated clinical activity in combination with anti-PD-1 monotherapy in advanced melanoma, with concordant clonal T cell expansion observed in the tumor and peripheral blood in patients with radiographic response. IO102-IO103 has not yet been assessed in combination with nivolumab-relatlimab (nivo-rela). Methods: In this multicenter, phase 2 trial (NCT05912244) patients with unresectable, previously untreated non-uveal melanoma were treated with subcutaneous IO102-IO103 and intravenous nivo-rela for up to two years. IO102-IO103 was administered every two weeks for eight weeks, and every four weeks thereafter. PD-L1 protein expression was assessed using the 28-8 pharmDx assay on pre-treatment tissue. The primary endpoint was best overall response rate (BORR) by RECIST v1.1, with a plan to reject the null hypothesis based on the proportion of patients with ≥1% membranous PD-L1 staining in the tumor compartment. Secondary endpoints included progression-free survival (PFS), safety assessed by Common Terminology Criteria for Adverse Events v 5.0, and duration of response (DOR). PFS and DOR were summarized using Kaplan-Meier methods. Bulk T cell receptor (TCR) sequencing was performed on peripheral blood mononuclear cells using an RNA-based assay at baseline, week 4 and week 8. Results: Among 43 evaluable patients, the BORR was 60% (95% confidence interval [CI]: 44-75%), including 19 patients with partial response and 7 patients with complete response. At database lock (Dec 1 2025), median follow up was 10.1 months (interquartile range 6.1-19.3). The median duration of response was not reached (95% CI: 14, NR) and median PFS was 8.2 months (95% CI 6.8, not reached [NR]). Among patients with PD-L1 negative tumors (n = 25), the BORR was 52% (95% CI 31-72%) and median PFS was 8.2 months (4.2, NR). Grade 3-4 treatment-related adverse events occurred in 9 patients (21%), including adrenal insufficiency (2 patients), acute kidney injury (2), aseptic meningitis (1), arthritis (1), maculopapular rash (1), myositis (1), neutropenia (1), and colitis (1). There were no treatment related deaths. T cell clonal expansion was observed at on-treatment time points compared to baseline in patients with and without radiographic response. Conclusions: IO102-IO103 in combination with nivo-rela was associated with a higher objective response rate compared to historical data for nivo-rela alone, meeting the trial’s primary endpoint. No unexpected safety signals were observed. These findings support the further clinical investigation of IO102-IO103 with nivo-rela as an initial treatment for unresectable melanoma. Clinical trial information: NCT05912244 .

Integrating a small extracellular vesicle protein–based ovarian cancer score with O-RADS Ultrasound to improve preoperative risk stratification of adnexal masses.

5555 Background: Accurate preoperative differentiation of adnexal masses remains a major clinical challenge. Although the Ovarian-Adnexal Reporting and Data System (O-RADS) standardizes ultrasound-based risk assessment, approximately 30-35% of adnexal masses are classified as indeterminate (O-RADS 3/4), often resulting in diagnostic uncertainty, unnecessary surgery, or delayed referral to gynecologic oncologists. Conventional serum biomarkers such as CA125 are limited by poor specificity and biological heterogeneity. The small Extracellular vesicle (sEV)-associated biomarkers have emerged as a promising approach to improve diagnostic accuracy by more closely reflecting tumor-related molecular signals. This study evaluated whether a serum sEV-based Ovarian Cancer Score (OCS) provides independent and incremental diagnostic value when integrated with O-RADS ultrasound. Methods: This retrospective diagnostic study included 250 consecutive patients with adnexal masses treated at Sun Yat-sen Memorial Hospital. All patients underwent standardized transvaginal ultrasound with O-RADS classification and serum CA125 testing. OCS was assessed using a chemiluminescent immunoassay based on serum sEV-derived CA125, HE4, and C5a. Final histopathology served as the reference standard. Diagnostic performance was evaluated overall and stratified by O-RADS category. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of malignancy. Results: Overall, OCS demonstrated significantly higher diagnostic accuracy for malignancy than serum CA125 alone. In masses with clearly benign or malignant imaging features (O-RADS 2 and 5), OCS maintained an accuracy of approximately 90% (87.5% and 94.6%). Within the clinically challenging O-RADS 3/4 subgroup (n = 115), OCS achieved a diagnostic accuracy of 86.1%, substantially outperforming serum CA125 (69.6%). Multivariate analysis identified OCS positivity as the strongest independent predictor of malignancy (OR 106.08, 95% CI 15.37-732.15, p &lt; 0.001), exceeding individual high-risk ultrasound features such as ascites or mixed cystic-solid components. Diagnostic performance was further enhanced when OCS was combined with selected ultrasound characteristics. Conclusions: A serum sEV-based OCS provides robust and independent diagnostic information that complements O-RADS ultrasound in the preoperative evaluation of adnexal masses. By addressing the diagnostic gray zone of O-RADS 3/4, this integrated approach extends beyond conventional serum biomarkers and may support improved risk stratification and triage decisions. Clinical trial information: NCT06366997 .

Neighborhood social vulnerability and clinical trial enrollment in colon cancer: Does age matter?

1533 Background: Colorectal cancer is now the leading cause of cancer-related death in people under 50, and young adults living in poverty have increased mortality. Despite younger age being associated with higher clinical trial enrollment, young adults face distinct social and structural barriers that may impede participation. This study examines how neighborhood social vulnerability is associated with clinical trial participation for colon cancer in young and older adults. Methods: Patients diagnosed with colon cancer were identified in the nationally representative Vizient Clinical Database from January 2022 – June 2025 and stratified into young adult (age 18-49) and older adult (50 and above) cohorts. The outcome of interest was clinical trial enrollment, identified by billing codes. Social vulnerability was defined by the Vizient Vulnerability Index in quartiles at the census tract level. Multivariable analyses were performed in both cohorts. An interaction analysis was performed between age and social vulnerability. Results: Of 234,047 patients, 15% were young adults, of which 5.1% enrolled in a clinical trial. Eighty-five percent were older adults, of which 3.0% enrolled in clinical trials. Most young adults had private insurance (73.1%) while most (56.6%) of the older patients were enrolled in Medicare. Non-Hispanic (NH) Black patients were less likely to enroll than NH White patients in both the young adult (OR 0.72, p=0.0001) and older adult cohorts (OR 0.79, p&lt;.0001), as were young and older patients with Medicaid vs. private insurance (OR 0.75, p=0.0001 and OR 0.71, p&lt;.0001, respectively). Diagnosis at an academic medical center vs. community hospital increased the odds of enrollment for both groups: young (OR 2.79, p&lt;.0001) and older (OR 2.04, p&lt;.0001), as did being married vs. single: OR 2.31, p=0.0016 for younger and OR 1.85, p&lt;.0001 for older adults. Among older adults only, Hispanic patients (OR 0.87, p=0.0056; ref NH White) and female patients (OR 0.91, p=0.0002; ref male) were less likely to enroll. Living in the most vs. least socially vulnerable neighborhoods impacted trial enrollment more for young adults (OR 0.75, p&lt;.001) than for older adults (OR 0.91, p&lt;.0001), p= 0.0042 for interaction. Conclusions: Many factors that influence trial enrollment, including insurance, social support, diagnosis at an academic center, and race/ethnicity, are similar among young and older adults with colon cancer. However, the negative impact of neighborhood disadvantage on trial enrollment is more pronounced among young adults, highlighting the need for practical trial design, targeted navigation, and strategic recruitment of young adults living in socially vulnerable areas.

RINGSIDE: A phase 3 randomized, placebo-controlled trial of varegacestat for treatment of progressing desmoid tumors.

11506 Background: Desmoid tumors (DT) are rare, locally aggressive tumors with few effective treatments. Varegacestat (VAR) is an investigational, once daily, oral gamma secretase inhibitor that previously showed antitumor activity in pts with DT in the RINGSIDE Phase 2 study. Methods: RINGSIDE Phase 3 was a double-blind, placebo (PBO)-controlled study in adults with progressing DT per RECIST v1.1 (NCT04871282). 156 pts were randomized 1:1 to once daily oral VAR 1.2 mg (n=79) or PBO (n=77). Imaging-based tumor response was assessed per RECIST v1.1 by blinded independent central review. The primary endpoint was progression-free survival (PFS). Alpha-controlled secondary endpoints were confirmed objective response rate (ORR), change in tumor volume (TV) at Week 24, and change in patient-reported worst pain intensity (WPI) at Week 12. Results: Demographics and disease characteristics were balanced between treatment arms. As of Oct 7, 2025, median duration of exposure was 20.3 months (range 0.8 – 34.6) for VAR and 11.1 months (range 0.2 – 34.6) for PBO. VAR demonstrated significantly better PFS compared with PBO (hazard ratio [HR]: 0.16 [95% CI: 0.07, 0.38; P &lt;0.0001]). PFS consistently favored VAR in all subgroups analyzed. ORR was significantly better with VAR vs PBO (55.7% vs 9.1%; P &lt;0.0001), with 3 CRs in the VAR arm and 1 CR in the PBO arm. Median duration of response was not reached in either arm. All alpha-controlled secondary endpoints demonstrated statistically and clinically significant superiority for VAR compared with PBO (Table). Overall, 95% of adverse events (AEs) were Grade 1-2 and there were no Grade 5 AEs. Grade 3/4 AEs were reported in 57% of VAR pts and 17% of PBO pts. AEs led to dose reduction in 63 (80%) VAR pts and 7 (9%) PBO pts; 16 (20%) VAR pts and 5 (7%) PBO pts discontinued due to AEs. In the VAR arm, the most frequently reported AEs were diarrhea (82%), fatigue (44%), and rash (43%). Ovarian toxicity occurred in 20/36 (56%) premenopausal women on VAR, resolved in 11/20 (55%), and did not lead to dose interruption or drug withdrawal. Conclusions: VAR demonstrated statistically significant and clinically meaningful antitumor activity and pain relief, achieving the highest ORR reported in a Phase 3 trial of systemic DT therapy, with no new safety signals. Clinical trial information: NCT04871282 . RINGSIDE phase 3 trial outcomes. VAR (n=79) PBO (n=77) HR (95% CI) or Difference; P value Median PFS (95% CI) - radiographic, months NE (NE, NE) 24.9 (13.8, NE) 0.16 (0.07, 0.38); P&lt;0.0001 Confirmed ORR, n (%) 44 (55.7) 7 (9.1) P&lt;0.0001 TV change (cm 3 ) at Week 24, LS mean (SE) -109.6 (40.64) 122.8 (42.72) -232.4 (57.39); P&lt;0.0001 WPI (pain) change at Week 12, LS mean (SE) -2.24 (0.27) 0.18 (0.27) -2.42 (0.37); P&lt;0.0001 Median best % change in TV* -83.4 11.3 * 1-year PFS, % (95% CI)* 94.2 (85.3, 97.8) 65.6 (52.3, 76.0) * 2-year PFS, % (95% CI)* 88.9 (77.9, 94.6) 56.7 (42.6, 68.6) * LS, least square; SE, standard error. *Not alpha-controlled endpoint.

Racial and ethnic differences in cardiovascular disease prevention and treatment amongst breast cancer survivors.

e23331 Background: Breast cancer is the second leading cause of cancer death among women in the U.S., and heart disease remains the leading non-cancer cause of death in this population. Specific breast cancer therapies are associated with cardiotoxicity, contributing to coronary artery disease (CAD) and heart failure (HF). Hypertension (HTN) and smoking increase the risk of both breast cancer and cardiovascular disease (CVD). Racial and ethnic disparities in breast cancer outcomes arise from multilevel factors, including environmental conditions, socioeconomic status, and healthcare access. Methods: This retrospective cohort study aimed to identify targets for improving cardiovascular prevention in breast cancer survivors from different racial and ethnic groups. We assessed the hypothesis that Black and Hispanic breast cancer survivors would have lower rates of adequate risk prevention via pharmacotherapy compared with other groups. Descriptive analyses using RStudio were conducted on a cohort of 3,606 breast cancer survivors treated within the University of Illinois Cancer Center. Results: Non-Hispanic Black breast cancer patients had the highest prevalence of cardiovascular diseases (CVD). Hispanic breast cancer patients of all races had the highest prevalence of Diabetes Mellitus (DM). 91 percent of Non-Hispanic Black breast cancer patients (712 of 783) with CVD (diagnosed with either CVA or CAD) were on statins and anticholesterol agents. This evidence is encouraging, and suggests that efforts are already being made to promote cardiovascular risk reduction in black patients with a higher risk profile. After performing a univariate analysis for differences across race/ethnicity, we saw a significant difference in the prevalence of current smokers, coronary artery disease (CAD), hypertension (HTN), heart failure (HF), diabetes, chronic kidney disease(CKD), and cerebrovascular disease (CVD). This highlights that there is a racial disparity in the rates of these comorbidities, especially in Non-Hispanic Blacks and Hispanics. Conclusions: In conclusion, we identified significant racial and ethnic differences in cardiovascular risk factors, yet we also found encouraging evidence of adequate preventive pharmacotherapy among survivors with established atherosclerotic disease. Additional targeted interventions are needed to reduce inequities in cardiovascular prevention among breast cancer survivors.

Endometrial cancer risk management in patients with Lynch syndrome at a tertiary community cancer center.

e22539 Background: Lynch syndrome (LS) is a genetic predisposition associated with germline alterations in the DNA mismatch repair pathway that increases the risk of endometrial cancer (EC) up to 10-fold among other cancer risks. Hysterectomy (H) is a definitive strategy for risk reduction offered after childbearing. Screening for EC with an endometrial biopsy (EMB) is a strategy for those who are not ready for surgery. However, the uptake and utility of EMB are unknown. We present data from a large retrospective cohort aiming to provide insight into these questions. Methods: We reviewed the EC risk management behaviors for 75 assigned females at birth with LS between 2006 and 2024 at a large tertiary community cancer center in Seattle, WA. Data collected include age, pathogenic variant (PV), personal and family history of cancer, gynecologic surgical history, EMB, and pathology findings at EMB and/or surgery. Results: Median age of the cohort at LS diagnosis was 44 years (21-87), and 42 and 33 patients were pre- and post-menopausal, respectively. Reasons for genetic testing included: diagnosis of LS-related cancer (n = 37), familial testing (n = 17), and family history of cancer (n = 21). 18 patients had a PV in MLH1, 21 in MSH2 , 21 in MSH6 , and 15 in PMS2 . Of the 75 patients, 44 (59%) had either H + bilateral salpingectomy (H-BS) or H + bilateral salpingo-oophorectomy (H-BSO) before (n = 14) or at LS diagnosis (n = 30); 19/44 had EC and all had H-BSO. Longitudinal follow-up information was available for the remaining 31 patients with a median follow-up time of 5.48 years (0.03, 18.62). 27/31 patients were older than 30 at some point during follow-up and were considered eligible for EMB. Nine patients underwent EMB (33%), including 2 patients who had the procedure immediately prior to surgery. One patient was found to have a precursor lesion on EMB and EC was found on subsequent H-BS. At the time of LS diagnosis, 45 patients had both a uterus and no diagnosis of EC. 25/45 patients (56%) underwent risk reducing surgery, 3 chose a H-BS and 22 H-BSO. No ovarian abnormalities were noted. There was trend favoring ovarian conservation in women aged &lt; 45 (p = 0.1, Fisher’s exact test). No differences were observed based on the gene involved. Of the 19 patients that chose to forego surgery,15 were eligible for screening, but only 4 (27%) patients underwent EMB. Conclusions: H-BSO is the most common EC risk reduction strategy in patients with LS. Receipt of a BSO is common and similar across mismatch repair genes. Uptake of EMB is low and a substantial fraction of at-risk patients don’t receive any EC risk management strategies. Further research is needed to identify patient and provider-specific factors contributing to the observed variation in risk management.

Iparomlimab and tuvonralimab (PD-1/CTLA-4 bifunctional antibody) monotherapy or combination therapy in patients with advanced solid tumors treated.

e23358 Background: Patients with advanced solid tumors that progress after first-line treatment, particularly after PD-(L)1 inhibitor therapy, face limited treatment options. Iparomlimab and Tuvonralimab (QL1706) exert PD-1 inhibition while preserving the ADCC effect of CTLA-4 to deplete Treg cells. the anti-CTLA-4 antibody was engineered to have a shorter elimination half-life (t1/2) to reduce its exposure and lower the risk of irAEs,achieving a balance of enhanced efficacy and reduced toxicity.This multicenter real-world study evaluates the clinical utility of QL1706 in patients with advanced solid tumors, with a particular focus on those receiving 2nd-line and beyond treatments, including in the immunotherapy rechallenge setting. Methods: We enrolled patients with histologically confirmed advanced solid tumors who had received QL1706 (monotherapy or combination) as 2nd-line and beyond treatment across six clinical centers. The primary endpoint was safety. Secondary endpoints included objective response rate (ORR),disease control rate (DCR), progression-free survival (PFS),and overall survival (OS). Results: As of December 31, 2025, 50 patients were evaluable (NSCLC, 24%; gastric, 16%; HCC, 14%; rectal, 14%; others, 32%). In the overall cohort(n = 50; median age 62.0; 70% male),the ORR was 26.0% (13/50; 95% CI, 13.4–38.6) and DCR was 88.0% (44/50; 95% CI, 78.7–97.3) according to RECIST version 1.1.The median PFS and OS have not yet been reached (with a median follow-up of 6.7 months).Robust disease control was maintained across later lines, with ORR of 42.9% (6/14) and DCR of 92.9% (13/14) in 3rd-line settings.In the immunotherapy rechallenge subgroup (n = 32; median age 65.0), QL1706 demonstrated encouraging activity despite prior PD-(L)1 failure, with an ORR of 18.8% (6/32; 95% CI, 4.0–33.1) and a DCR of 84.4% (27/32; 95% CI, 71.1–97.7). At a median follow-up of 6.3 months, median PFS was 7.5 months (95% CI, 4.1–10.9), median OS was not yet reached.In the overall population,immune-related adverse events (irAEs) occurred in 26% of patients. Notably, Grade 3 irAEs were limited to 5.4% (primarily pneumonitis and elevated AST), showing a more favorable safety profile compared to historical anti-PD-1/CTLA-4 combination therapies. No treatment-related deaths were reported. Conclusions: In this study, QL1706 demonstrated a manageable safety profile and encouraging antitumor activity in patients with advanced solid tumors as 2nd-line and beyond treatment.Notably, QL1706 could be a potential treatment regimen for patients receiving immunotherapy rechallenge after prior PD-(L)1 failure. Clinical trial information: ChiCTR2500106339.

Geographic clustering of renal cell carcinoma in West Virginia counties with historical perfluorooctanoic acid (PFOA) exposure.

e16525 Background: Perfluorooctanoic acid (PFOA), a persistent per- and polyfluoroalkyl substance (PFAS), has contaminated multiple regions of West Virginia (WV) through historical industrial activity. We evaluated whether WV counties with documented PFOA exposure demonstrate increased renal cell carcinoma (RCC) prevalence compared with statewide rates and whether similar patterns are observed for other malignancies. Methods: We conducted a county-level ecological analysis of all 55 WV counties using Epic electronic health record–derived cancer data from 2015–2025. RCC cases included all histologic subtypes of renal cell carcinoma and explicitly excluded urothelial malignancies of the renal pelvis. County-specific prevalence rates were calculated using county population denominators. Crude relative risk (RR) estimates with 95% confidence intervals (CI) were calculated relative to statewide RCC prevalence using Poisson-based methods. Lung, colorectal, prostate, thyroid, and bladder cancers were analyzed as comparators to assess cancer specificity, with bladder cancer included as a urothelial malignancy distinct from renal parenchymal tumors. National kidney cancer incidence rates, which include renal pelvis cancers, were used solely for population-level contextual comparison and not as histology-matched comparators to RCC. Results: Between 2015 and 2025, 205 RCC cases were identified statewide in WVU-affiliated hospital systems. Counties with documented or suspected PFOA exposure—defined by proximity to known PFAS-contaminated industrial sites, historical aqueous film-forming foam use, or contaminated groundwater or public water systems—demonstrated significantly elevated RCC prevalence. Statistically significant increases were observed in Berkeley (RR 2.80, 95% CI 1.95–4.03), Harrison (RR 2.94, 95% CI 1.83–4.72), Jefferson (RR 3.10, 95% CI 1.93–4.98), Morgan (RR 3.21, 95% CI 1.43–7.25), and Lewis (RR 5.29, 95% CI 2.71–10.33) counties. All associations were statistically significant (p &lt; 0.05). These counties cluster in the Eastern Panhandle and north-central regions of West Virginia, regions with historical industrial activity, documented PFAS contamination, and downstream groundwater migration. No similar geographic clustering was observed for comparator cancers. Conclusions: WV counties with historical PFOA exposure demonstrate substantially increased RCC prevalence. This geographic specificity is biologically plausible, as PFAS undergo renal tubular reabsorption, leading to intrarenal accumulation and prolonged tissue residence, a pathway associated with chronic tubular injury and renal carcinogenesis. These findings support exposure-informed cancer surveillance and further analytic studies in environmentally impacted Appalachian communities.

Temperature‐Responsive Evolution and Mechanism Exploration of Static and Dynamic Solvation Structures in Localized High‐Concentration Electrolytes

ABSTRACT Solvation structures in localized high‐concentration electrolytes (LHCEs) critically govern ion transport and interfacial reactions. However, the temperature mismatch between characterization condition and actual operating environment has been usually overlooked, obscuring mechanistic interpretations of electrochemical performances. As a key parameter, temperature exerts a pronounced influence on intermolecular interactions in electrolytes. Here, we systematically elucidated the temperature responsiveness and underlying mechanism of solvation structures in LHCEs with varied compositions. It integrates in situ variable‐temperature small‐angle X‐ray scattering (SAXS) and Raman spectroscopy with molecular dynamics (MD) simulations and density functional theory (DFT) calculations. Beyond conventional static descriptors including coordination number (CN), radial distribution function (RDF) and cluster population, dynamic metrics including activity factor, cluster lifetime and ligand‐exchange event probability were also proposed to construct a unified static–dynamic framework for solvation‐structure evolution with temperature variation. Results show that elevating temperature attenuates solvation‐structure disparities arising from compositional difference. Moreover, high‐diluent electrolytes display distinctly different temperature sensitivity in static structural parameters versus dynamic metrics. Meanwhile, an ordered sequence of cluster transition process was revealed, wherein incorporation of an anion precedes dissociation of a solvent molecule. This work disentangles the coupled concentration–temperature effects on solvation structures in LHCEs and establishes the comprehensive understanding of structural evolution across wide temperature ranges, which provides experimentally validated theoretical guidance for the rational design of advanced electrolytes with superior interfacial stability and cycling performances.

Crystallographic bibliography of Co-precipitate derived (311) Guite (Co3O4) crystalline materials

Suppressing Surface Degradation in Na‐Rich Prussian Blue Cathodes via Liquid‐Phase Dehydration

ABSTRACT Na‐rich Prussian Blue (PB) is an attractive sodium‐ion battery cathode owing to its high capacity and low cost, yet approximately 10 wt.% of crystal water in its framework induces electrolyte side reactions and Fe dissolution. Conventional thermal dehydration has been used to remove crystal water, but it consistently results in capacity fading and poor air stability. Here, the primary cause of degradation is experimentally demonstrated to be surface oxidation driven by Fe–O bond formation during heat treatment. Guided by this insight, a liquid‐phase, low‐temperature dehydration strategy based on nitrogen bubbling is introduced, which simultaneously eliminates crystal water and stabilizes the surface. The approach can be seamlessly integrated into electrode fabrication to minimize air exposure and improve cycling stability. Overall, this work clarifies the mechanistic role of surface oxidation in moisture‐sensitive PB cathodes and highlights the critical importance of surface chemistry control in achieving stable electrochemical performance.

Prediction of syncope recurrence after percutaneous closure of patent foramen ovale based on machine learning