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Progression patterns and management after frontline platinum in advanced epithelial ovarian cancer (EOC).

e17581 Background: Most patients with EOC relapse after frontline platinum-based chemotherapy, even with maintenance therapy. Oligoprogression may define a distinct, locally treatable relapse pattern. Methods: We retrospectively analyzed advanced EOC patients treated at our institution (January/2014–December/2024) with surgery and platinum-based chemotherapy, or achieving radiologic complete response after frontline platinum chemotherapy without surgery. Progression was categorized as oligoprogression (1–5 lesions; group A) or multiple progression (group B). Associations were assessed using chi-square tests. Survival outcomes were estimated by Kaplan–Meier and compared by Cox regression. Baseline characteristics are summarized in the Table. Results: Among 107 patients (mean age 65±9.3 years), 75 (70%) relapsed and 29/75 (39%) had oligoprogression. Group A had a higher rate of frontline PARP inhibitor (PARPi) maintenance than group B (14/15 vs 11/35; p=0.02) and fewer metastatic sites at relapse (p=0.01). In the overall cohort, progression-free survival (PFS) >12 months from the end of frontline chemotherapy was associated with a higher likelihood of receiving local vs systemic therapy (p=0.002). In group A, median overall survival (OS) was 110.4±32.4 months and median PFS was 12.5±0.88 months. Local therapy (surgery and/or radiotherapy) versus systemic therapy was associated with longer OS (102.6 vs 34.3 months; p<0.001) and PFS (18.8 vs 9.4 months; p=0.003). Maintenance duration >12 months showed a trend toward longer PFS (25.4 vs 13.4 months; p=0.053). Excluding bevacizumab, PARPi >12 months versus ≤12/no maintenance showed a non-significant trend toward longer PFS (24.5 vs 13.1 months; p=0.10). Conclusions: In this real-world cohort, frontline PARPi maintenance was associated with a higher proportion of oligoprogressive relapse. Among oligoprogressive patients, local therapy was associated with clinically meaningful OS and PFS prolongation, supporting its consideration within multidisciplinary post-progression management. Characteristic Group A (n=29) (%) Group B (n=46) (%) Stage III / IV 51.7 / 48.3 69.6 / 30.4 Debulking surgery(S)/ Interval S/ no S 37.9 / 58.6 / 3.4 43.5/ 54.3 / 2.2 Chemotherapy (CT): neoadjuvant / adjuvant / palliative 58.6 / 31 / 10.3 50 / 39.1 / 10.9 HRD status: HRD+/ BRCA +, HRD+/ BRCA -, HRP, unknown 10.3 / 0 / 10.3 / 79.3 4.3 / 0 / 10.9 / 84.8 Germline BRCA status: BRCA1 / BRCA2 / wild-type / unknown 6.9 / 13.8 / 55.2 / 24.1 8.7 / 2.2 / 71.7 / 17.4 Maintenance therapy: bevacizumab / PARPi/ no maintenance 13.8 / 48.3/ 37.9 16.7 / 23.9/ 59.4 Relapse metastatic sites: 1 / 2 / 3 / 4 / 5 86.2 / 13.8 / 0 / 0 / 0 54.3 / 32.6 / 13 / 0 / 0 Progression sites (non-mutually exclusive): peritoneal/lymph nodes/liver/pleura/other 62.1 / 24.1 / 10.3 / 3.4 / 20.6 82.6 / 41.3 / 15.2 / 15.2 / 6.5 Treatment at relapse: S/radiotherapy/CT/S and CT/no therapy 31 / 6.9 / 34.5 / 24.1 / 3.4 0 / 0 / 93.5 / 4.3 / 2.2

Neoadjuvant DAN-222 plus niraparib in high-risk HER2-negative breast cancer: Results from the I-SPY 2 adaptive platform trial.

625 Background: I-SPY 2 is a multicenter phase II adaptive platform trial evaluating novel agents for stage II-III high-risk breast cancer using response-predictive subtypes (RPS) and a sequential neoadjuvant treatment design of up to three blocks (A/B/C). Investigational regimens are given in Block A, followed by response-guided escalation to standard-of-care (SOC) therapy (tx) in subsequent blocks or early surgery for responders. Topoisomerase I (TOPO1) inhibition plus PARP inhibition may enhance DNA damage and tumor response. DAN-222 is a tumor-targeted polymeric camptothecin conjugate designed to improve the therapeutic index of TOPO1 inhibition. Based on favorable phase 1 safety and preliminary activity in metastatic breast cancer, DAN-222 plus niraparib was evaluated as Block A tx in HER2− disease. Notably, the neoadjuvant regimen used a higher dose of niraparib (200 mg daily) than the prior phase 1 metastatic study. Methods: Patients (pts) with HER2− breast cancer were randomized to DAN-222 plus niraparib for up to 12 weeks in Block A. Response was assessed by serial MRI and biopsy. Inadequate responders escalated early to SOC tx in Blocks B/C. Primary endpoint was pathologic complete response (pCR). Secondary endpoints included residual cancer burden, safety, early discontinuation, and treatment-strategy performance versus subtype-specific SOC tx controls. Given established PARPi sensitivity in BRCA mut disease, the key objective was to assess clinically meaningful activity of DAN-222 plus niraparib in BRCA wt pts. Accordingly, a prespecified Bayesian interim futility analysis focused on BRCA wt and tested the probability of the true pCR rate after Block A alone exceeded 15% after 50 pts. Results: Fifty pts enrolled from Sep to Dec 2024. In BRCA wt (n=47), estimated Block A pCR was 3%, with posterior probability of 0.02 that that true pCR exceeded 15%, meeting futility criteria and prompting arm closure. Across all blocks, pCR rate was 57% (8/14) for HR-HER2−; 11% (4/36) for HR+ HER2−, largely after SOC tx. 2/3 BRCA mut pts achieved pCR. Treatment strategies initiating with DAN-222 plus niraparib underperformed subtype-specific controls. 68% discontinued Block A early, mainly due to toxicity. Grade ≥3 cytopenias were common: neutropenia (n=25; 50%), anemia (24%), and thrombocytopenia (18%). Cystitis occurred in 36% (1 grade ≥3). Conclusions: Neoadjuvant DAN-222 plus niraparib showed insufficient activity and no treatment-strategy benefit in BRCA wt HER2− breast cancer, underscoring challenges for TOPO1–PARP inhibitor combinations. Although not supported for further development in this setting, these results highlight the strength of I-SPY 2 in rapidly enrolling patients and quickly distinguishing ineffective from promising therapeutic strategies to accelerate progress toward improved outcomes for patients with curable breast cancer. Clinical trial information: NCT01042379 .

Utilization of germline genetic testing in prostate, pancreatic, and ovarian cancer in a rural setting.

e22634 Background: Prostate, pancreatic, and ovarian cancer are malignancies with known high prevalences of pathogenic germline variants strongly associated with development of these malignancies. The implications for germline genetic testing (GGT) are significant and can have a substantial impact on patient care, treatment decisions, and prognostication. Furthermore, GGT can identify unaffected family members who may benefit from cancer screening and/or interventions to reduce their risk of various cancers. As of 2019, National Comprehensive Cancer Network (NCCN) guidelines recommend universal GGT for high/very-high risk localized or metastatic prostate cancer, exocrine pancreatic cancer, and epithelial ovarian cancer. Despite this recommendation, low rates of genetic counseling (GC) referrals and GGT are well-recognized concerns within the field. Therefore, we sought to determine the rates of GC referrals and GGT at our rural-based institution for the aforementioned cancers. Methods: Following IRB approval, we identified all adult patients diagnosed in our health system between January 2020 and January 2024 with high/very-high risk localized prostate cancer, node-positive/metastatic prostate cancer, epithelial ovarian cancer, and exocrine pancreatic cancer. Those who previously had undergone GGT for hereditary cancer evaluation were excluded. Via retrospective review of patient electronic health records, we captured demographics, disease-specific variables, and data regarding GC appointments, patient access, and GGT by cancer type. Results: Six hundred twenty-one patients met study inclusion criteria: (55% prostate, 31% pancreatic, 13% ovarian). Our sample was 98% White, 74% male, 53% current/former smoker, had a median age of 71 years, and 63% lived in a non-metropolitan area. Most patients had stage III or IV disease (72%). In total, 168 (27%) had a GC order (16% prostate, 26% pancreatic, 75% ovarian; p < 0.01), 106 (17%) completed a GC appointment (9.6% prostate, 13% pancreatic, 58% ovarian; p < 0.01), and 106 (17%) underwent GGT (9.6% prostate, 14% pancreatic, 55% ovarian; p< 0.01). Median time from diagnosis to GC appointment was 129 days (148 prostate, 115 pancreatic, 129 ovarian; p = 0.3). Most GC orders were placed by medical oncology (72%), followed by radiation oncology (17%). Conclusions: Despite clear NCCN recommendations for universal testing for high/very-high risk localized or metastatic prostate cancer, pancreatic cancer, and ovarian cancer, our institution has very low rates of GC referrals and GGT. Ovarian cancer had the highest rates of GC and GGT (58% and 55%, respectively), rates still far from optimal. Despite low rates of GGT in these cancers, our data appear consistent with national trends for GGT (10% prostate, 22% pancreatic, 55% ovarian). A future study will identify barriers to GC and GGT and propose strategies to increase GGT rates at our institution.

CTNow pilot study: A multilevel clinical trial education and clinical trial referral coordination intervention for rural oncology providers and patients with cancer.

TPS1676 Background: Enhancing patient access to cancer clinical trials is an ASCO and NCI priority. Major barriers to clinical trial access in rural areas include limited awareness and knowledge of available cancer clinical trials among both rural oncology providers and patients with cancer. Our preliminary research found that only 9% of rural cancer patients have knowledge of clinical trials, and many providers lack the time or resources to discuss them in clinical settings. Hawaiʻi’s geographic isolation presents persistent barriers to clinical trial access, particularly for residents of the five rural neighbor islands of Hawaiʻi. Expanding clinical trial access requires not only increasing infrastructure and trial availability; enhancing provider and patient awareness and knowledge is a critical step toward improving access to trials in rural communities. A coordinated, culturally informed, and statewide approach is urgently needed to build trust, increase literacy on clinical research participation, and ensure that clinical trials become an equitable part of standard cancer care for all communities in Hawaiʻi. This pilot trial evaluates the preliminary efficacy of CTNow , a novel multilevel, multicomponent clinical trial education and clinical trial referral coordination intervention designed for rural oncology providers and patients with cancer. Methods: This multi-site pilot trial is currently open in three rural counties in Hawai‘i. The multilevel CTNow intervention includes: 1) two interactive webinar sessions for rural oncology providers; 2) a tablet-based multimedia education program for patients; and 3) referral resources for providers and an optional video chat feature for patients to connect with clinical trials staff for questions and/or referrals to trials. The study team developed intervention components that provide rural-specific provider clinical trial information, along with evidence-based patient education materials adapted for varying levels of health literacy. Key patient inclusion criteria include patient self-report of cancer diagnosis, current/past/planned treatment, and residency in rural areas. Provider participants include rural-based oncologists and advanced practice providers not currently involved in clinical trials. Planned enrollment includes 30 patients with any cancer type and 5 oncology providers practicing in rural Hawaii. The primary endpoint is within-patient and within-provider changes in knowledge of cancer clinical trials from baseline. Secondary endpoints include changes in attitudes toward clinical trials and self-efficacy related to trial participation, and utilization of video chat sessions. Enrollment began in March 2025. To date, 80% of patients and 100% of planned providers have been enrolled. Clinical trial information: NCT06237816 .

A phase II study of HB0025 (a PD-L1/VEGF bispecific antibody) in combination with chemotherapy as first-line treatment for non–small cell lung cancer (NSCLC).

8574 Background: HB0025, developed by Huaota, is a novel anti-PD-L1/VEGF bispecific antibody with VEGFR1D2 linked at the N-terminal of anti-PD-L1 antibody. This Phase II study assesses the efficacy and safety of HB0025 combined with chemotherapy in locally advanced unresectable, recurrent or metastatic non-small cell lung cancer (NSCLC). Methods: This open-label, multi-center, Phase II trial enrolled previously untreated patients with locally advanced unresectable, recurrent or metastatic NSCLC, without EGFR or ALK gene alterations. Participants were assigned to two cohorts: Cohort 1 (squamous NSCLC) received 20 mg/kg HB0025 plus carboplatin and paclitaxel every three weeks (Q3W) for 4-6 cycles, followed by HB0025 maintenance; Cohort 2 (non-squamous NSCLC) received 20 mg/kg HB0025 plus carboplatin and pemetrexed Q3W for 4-6 cycles, followed by maintenance with HB0025 and pemetrexed. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: As of January 5, 2026, 125 patients were enrolled in the study (62 patients in Cohort 1 and 63 patients in Cohort 2). The median age was 65 years old (range: 34, 74). The median follow-up period was 10.55 months (range: 1.0, 17.4). A total of 119 patients had at least one post-baseline tumor assessment. In Cohort 1, ORR was 84.5% (49/58), with subgroup ORRs of 81.3%, 72.2%, and 100% for PD-L1 TPS < 1%, 1–49%, and ≥50%, respectively; disease control rate (DCR) was 94.8% (55/58), median progression-free survival (mPFS) was 12.62 months, and median duration of response (mDOR) was immature. In Cohort 2, ORR was 65.6% (40/61), with ORRs uniformly 66.7% across all PD-L1 TPS subgroups; DCR was 96.7% (59/61), mPFS was 14.65 months, and mDOR was 12.06 months. Overall survival data remained immature. The most common immune-related adverse events (irAEs) were hypothyroidism (7.2%), hyperthyroidism (4.8%), increased alanine aminotransferase (4.0%), increased aspartate aminotransferase (3.2%), and increased blood thyroid stimulating hormone (3.2%). Anti-VEGF-related AEs of grade ≥3 were proteinuria (8.8%), hypertension (6.4%), hemorrhage (4.0%), and thromboembolism (4.0%). 6 (4.8%) patients discontinued HB0025 due to TRAE, and 2 (1.6%) patients died due to TRAE. Conclusions: The combination of HB0025 and chemotherapy has demonstrated promising efficacy and favorable safety as a first-line treatment for patients with locally advanced unresectable, recurrent or metastatic NSCLC. Multi-center, randomized, double-blind, controlled phase III trials in both squamous and non-squamous NSCLC have been initiated. Clinical trial information: NCT06758557 .

A 3-year landmark overall survival analysis of RP1 plus nivolumab in patients with anti–PD-1–failed melanoma from the IGNYTE clinical trial.

9518 Background: Advanced melanoma has a high mortality rate; however, survival for patients (pts) treated with anti–PD-1–based therapy tends to plateau at 3–4 years, suggesting that pts alive at 3 years are likely to have prolonged benefit. This highlights the need for novel therapies that offer increased survival beyond 3-4 years. RP1 (vusolimogene oderparepvec) is an HSV-1–based oncolytic immunotherapy expressing GM-CSF and a fusogenic glycoprotein (GALV-GP-R − ). In the IGNYTE trial (data cutoff [DCO]: 15OCT2024), pts with advanced melanoma that had confirmed progression on anti–PD-1 therapy who received RP1 + nivolumab (nivo) had an objective response rate by RECIST 1.1 of 33.6% (16.4% complete response); median duration of response was 24.8 months. Here, we present a 3-year survival analysis of pts treated with RP1 + nivo from IGNYTE (last pt in: 9MAR2023; DCO: 11JUN2025). Methods: Pts ≥18 years with advanced melanoma and confirmed progression while being treated for ≥8 weeks with anti–PD-1 ± anti–CTLA-4 as the last prior therapy were enrolled (NCT03767348). An initial dose of RP1 was administered intratumorally (1 × 10 6 PFU/mL), followed by up to 7 doses every 2 weeks (Q2W; 1 × 10 7 PFU/mL) in combination with intravenous nivo 240 mg Q2W/480 mg Q4W for up to 2 years; additional RP1 was allowed if protocol-specified criteria were met. This updated analysis evaluated overall survival (OS) using the Kaplan-Meier (KM) method. Results: Of 140 enrolled pts, 49.3% had stage IVM1b–d disease, 55.7% had PD-L1–negative tumors, 46.4% had prior anti–PD-1 + anti–CTLA-4 therapy, and 65.0% had primary resistance to prior anti–PD-1 (ie, progression within 6 months of starting the immediate prior course of anti–PD-1). The median (95% CI) OS was 32.2 (25.8, 39.2) months (the median OS follow-up was 3 years by reverse KM method). OS rates (95% CI) at 1, 2, and 3 years were 75.3% (66.9%, 81.9%), 61.6% (52.5%, 69.4%), and 45.5% (35.8%, 54.7%), respectively. Importantly, among responders (n=47), the 3-year OS rate (95% CI) was 81.8% (65.2%, 91.0%) vs 22.5% (12.6%, 34.2%) for non-responders (n=93). The 3-year OS rates were 41.8% in pts with stage IVM1b–d disease (n=69), 37.2% for those with PD-L1–negative tumors (n=78), 37.4% in pts with prior anti–PD-1 + anti–CTLA-4 therapy (n=65), and 44.8% in pts with primary resistance to anti–PD-1 (n=91). The safety profile for RP1 + nivo remained consistent with prior reports; no new safety signals were seen. Conclusions: The 3-year landmark OS rate of 45.5% in the overall population and 81.8% among responders provides further evidence that the deep and durable responses provided by RP1 + nivo translate into long term clinical benefit, including extended OS in pts with melanoma post-confirmed progression on prior anti–PD-1–based therapy. Clinical trial information: NCT03767348 .

Synergistic efficacy of intrathecal PD-1 blockade combined with whole-brain radiotherapy for melanoma leptomeningeal metastases: A real-world analysis.

e14023 Background: Leptomeningeal metastasis (LM) from malignant melanoma remains a catastrophic event with a historical median survival of <3 months. While intrathecal (IT) administration of PD-1 antibodies has shown preliminary efficacy, the potential synergy between radiotherapy-induced immunogenic cell death and compartmentalized checkpoint blockade remains unexplored. We investigated the safety and survival impact of combining WBRT with IT PD-1 antibody therapy in this high-risk population. Methods: We retrospectively analyzed consecutive patients with melanoma LM treated with IT PD-1 antibodies at a single center between June 2022 and December 2024. The cohort was stratified by treatment modality: IT Monotherapy vs. Combination Therapy (WBRT delivered within 30 days of IT PD-1 initiation). The primary endpoints were overall survival (OS) and intracranial progression-free survival (iPFS), assessed by Kaplan-Meier analysis and Log-rank tests. Safety was rigorously graded per NCI-CTCAE v5.0, with specific focus on neurotoxicity and immune-related adverse events (irAEs). Results: A total of 20 patients were enrolled (Combination: n=13; Monotherapy: n=7). Baseline characteristics were well-balanced. The Combination arm achieved a striking survival advantage, with a median OS of 45.3 weeks (95% CI 28.7–NR) compared to 20.1 weeks (95% CI 13.3–NR) in the Monotherapy arm (HR 0.30 [95% CI, 0.04-0.68]; P = 0.021). Similarly, median iPFS was more than doubled in the Combination group (23.0 vs. 10.0 weeks; P < 0.001). The regimen was well-tolerated; there was no statistically significant difference in the incidence of Grade ≥2 adverse events between groups, and no unexpected severe neurotoxicity was observed. Conclusions: Concurrent WBRT and IT PD-1 blockade demonstrates potent synergistic activity in melanoma LM, delivering unprecedented survival outcomes (median OS >10 months) without amplifying toxicity. These findings suggest that radiotherapy may prime the CSF microenvironment for enhanced immune checkpoint efficacy. This novel multimodal strategy warrants validation in prospective randomized trials as a potential new standard of care.

Yttrium-90 SIRT plus atezolizumab/bevacizumab in unresectable huge HCC (>10 cm): A multicenter retrospective study.

4144 Background: Huge hepatocellular carcinoma ((huge HCC, ≥ 10 cm)) has poor prognosis with limited systemic therapy efficacy. We evaluated Y-90 selective internal radiation therapy (SIRT) combined with atezolizumab plus bevacizumab (Atezo/Bev) in this population. Methods: This retrospective multicenter study enrolled 21 patients with unresectable huge HCC (maximum diameter >10 cm) treated with Y-90 SIRT plus Atezo/Bev from January 2023 to July 2025. Eligibility criteria included Child-Pugh class A/B, ECOG performance status 0/1, and completion of ≥2 treatment cycles. The primary endpoint was ORR assessed by mRECIST. Secondary endpoints: PFS, OS, and safety (CTCAE v5.0). Results: Among the patients median tumor diameter 116.2 mm (IQR 105.6-131.9); >15 cm 14.3%; BCLC C 76.2%; PVTT 76.2%; extrahepatic metastasis 23.8%. The objective response rate (ORR) was 61.9% (13/21), including 6 (28.6%) complete responses (CR) and 7 (33.3%) partial responses (PR). The disease control rate (DCR) was 76.2% (16/21), with 3 (14.3%) stable disease (SD) and 5 (23.8%) progressive disease (PD). Median follow-up 11.0 months (IQR 7.1-25.0). Respectively, the median OS was not reached, at data cutoff, the 6- and 12-month PFS rates were 65.1% and 27.1%, respectively. The 6-, 12-, and 24-month OS rates were 76.2%, 57.5%, and 49.3%. Radiological responders (CR/PR) showed reduced progression risk (HR 0.46; 95% CI 0.16-1.32) and death risk (HR 0.41; 95% CI 0.11-1.49) vs non-responders. Nonrim APHE correlated with improved survival (median OS: 18.0 vs 8.0 months; HR 0.54). Grade ≥3 treatment-related adverse events occurred in 14.3% (3/21): pneumonia (n=2), hepatic encephalopathy (n=1). No treatment-related deaths. Conclusions: In this cohort, Y-90 SIRT plus Atezo/Bev achieved 61.9% ORR with manageable toxicity. These findings warrant prospective trials. Baseline characteristics and clinical outcomes (N=21). Characteristic Value Age, median (range), years 53 (28–76) Male sex, n (%) 18 (85.7) ECOG performance status 0/1, n (%) 16 (76.2) / 5 (23.8) Etiology HBV/Alcohol/Unknown, n (%) 18 (85.7) / 1 (4.8) / 2 (9.5) Tumor diameter, median (IQR), mm 116.2 (105.6–131.9) Tumor >15 cm, n (%) 3 (14.3) BCLC stage A/B/C, n (%) 4 (19.0) / 1 (4.8) / 16 (76.2) Child-Pugh A/B, n (%) 17 (81.0) / 4 (19.0) Portal vein tumor thrombus, n (%) 17 (81.0) Extrahepatic metastasis, n (%) 5 (23.8) AFP >400 ng/mL, n (%) 10 (47.6) Complete responses (CR) 6 (28.6%) Partial responses (PR) 7 (33.3%) Stable disease(SD) 3 (14.3%) Progressive disease (PD) 5 (23.8%) Objective response rate (ORR) 61.9% (13/21) Disease control rate (DCR) 76.2% (16/21) Median follow-up, months 11.0(IQR 7.1-25.0) 6- and 12-month PFS rates 65.1% and 27.1% 6-, 12-, and 24-month OS rates 76.2%, 57.5%, and 49.3% Grade ≥3 TARE 14.3% (3/21) TARE: treatment-related adverse events.

Phase I study of IMM2510, a PD-L1/ VEGF bispecific antibody, in participants with advanced IO-treated SQ-NSCLC.

8580 Background: Despite advancements in first-line treatments such as immunotherapy and targeted therapies, resistance to these treatments is common, especially those IO-treated and low PD-L1 TPS, creating a significant unmet need for effective second-line therapies. IMM2510 is a bispecific fusion protein targeting PD-L1 and VEGF which can modify tumor microenvironment to overcome resistance and improve sensibility to antitumor agents. The data of dose-escalation phase I was previously reported in ASCO2024. Here we summarize the updated efficacy and safety results of IMM2510 in advanced IO-treated SQ-NSCLC. Part of the data were previously reported in WCLC 2025. Methods: The phase I study was designed as a first-in-human, open-label, multi-center study to evaluate the safety, efficacy, PK and PD of IMM2510 in pts with advanced solid tumors. Eligible pts were enrolled to receive IMM2510 via intravenous infusion Q2W. Results: As of 31 Dec 2025, 32 pts with advanced IO-treated SQ-NSCLC received IMM2510. The median age was 61 years; 31.3% pts had PD-L1 TPS < 1%; 75.0% pts had ECOG score of 1; the median prior lines of anti-tumor therapy were 2 (range: 1-5). All 32 pts experienced TEAEs. Grade ≥3 TEAEs were reported by 17 (53.1%) pts; Grade ≥3 TRAEs were reported by 12 (37.5%) pts; TRAEs leading to treatment discontinuation were reported by 1 (3.1%) participant. No participant experienced TRAE leading to death. 22 pts with advanced IO-treated SQ-NSCLC were evaluable for efficacy analysis. The ORR was 27.3% (6/22) and DCR was 81.8% (18/22). The median DoR was 11.1 months. The median PFS was 9.4 months at the median follow-up time of 8.3 months. The median overall survival was not reached. Exposure-response (ER) analysis within the 3 - 20 mg/kg dose range revealed a positive exposure-efficacy relationship in pts with SQ-NSCLC, with higher exposure corresponding to increased ORR or DCR, while a relatively flat ER was observed for Grade 3 or higher TRAE and most common AEs in NSCLC. Thus, 20 mg/kg Q2W was selected as the RP2D with well-balanced efficacy-safety profiles. Conclusions: In pts with advanced IO-treated SQ-NSCLC, IMM2510 provides clinical meaningful benefit and supports a favorable benefit-risk profile. The phase III clinical study is being planned. Clinical trial information: NCT05972460 .

HealthTree survey as an identifier of venous thromboembolism risk mitigation targets in newly diagnosed multiple myeloma.

e19580 Background: Patients (pts) with newly diagnosed multiple myeloma (NDMM) are at significantly increased risk of venous thromboembolism (VTE). Lack of awareness, appropriate pt counseling and inconsistent performance of risk stratification tools are barriers to effective risk mitigation. Methods: A cross-sectional survey of 579 NDMM pts was conducted via HealthTree. Overall incidence of VTE and SAVED / IMPEDE risk scores were retrospectively calculated using participant electronic health records. Associations between risk mitigation strategies, thrombotic events, types of prophylaxis (ppx) and bleeding rates were evaluated using chi-squared and ANOVA tests with Benjamini-Hochberg adjustments. Results: Median (Q1,Q3) age was 69 (63,73), 88% White, 7% African-American, and 89% received an IMiD-based induction. Incidence of new VTE at any time was 35%, of which 22% occurred in the first year since diagnosis, and additional 13% after year 1. Rate of new/recurrent VTE after year 1 was 20%. Having an academic/myeloma specialist for a provider vs not, pts were less likely to develop a VTE (31% vs 39%). Pt history of prior DVT or PE was a highly significant predictor of VTE vs not (relative risk 2.61, 39% vs 9%). Pts who had a discussion on the risk of VTE (58%) vs not or who did not remember (42%) had a 23.6% lower relative risk of developing a VTE. Similarly, discussing the risk of VTE plus using VTE ppx within the year 1 of diagnosis vs missing either or both had the greatest reduction in the risk of VTE (12-22%, p = 0.001, Table 1). Median (Q1,Q3) SAVED score was 4 (4,5) for both pts who experienced vs not VTE at any time. Median (Q1,Q3) IMPEDE score was 8 (7,10) for pts who experienced VTE at any time, vs 9 (8,10) for those who never had VTE. Overall, 34% of pts were on no VTE ppx of any kind at any point. Among those who suffered VTE at any point, 42% were not on any VTE ppx, 35% were on aspirin (ASA), and 20% were on apixaban or rivaroxaban (api/riva). Of those who were on VTE ppx and suffered VTE vs not, 19% vs 11% had a bleeding event (p = 0.024), with major bleeding rates of 16% vs 9%, respectively (p = 0.021). Overall, 35% of pts with bleeding events were on ASA, and 54% were on api/riva. In all pts with VTE, only 36% received full care as outpatient; 58% had to preset to the emergency room (ER), of which 23% did not need hospital admission, 20% needed one without an intensive care unit (ICU), and 15% needed ICU care. Conclusions: We present the highest VTE incidence rate in NDMM reported in the literature. VTE risk remains present within the first year of diagnosis and beyond. Receiving care by an academic or myeloma specialist, having a discussion on VTE risk and utilising VTE ppx were all factors which mitigated VTE risk. SAVED and IMPEDE scores were not reliably discriminating for the VTE risk, and 77% of pts who had VTE were on no VTE ppx or ASA. Healthcare utilisation rate for VTE management is significant, with over half pts needing ER care.

Clinical utility of comprehensive molecular profiling in cholangiocarcinoma.

e16206 Background: Cholangiocarcinoma (CCA) comprises a heterogeneous group of biliary tract malignancies with distinct molecular types and features and increasing therapeutic relevance. Comprehensive genomic profiling is essential for clinical actionability, diagnostic relevance, and potential impact on therapeutic decision-making. The purpose of this study is to define the molecular profile of cholangiocarcinoma through a comprehensive Next Generation Sequencing (NGS) panel and to assess its implications for diagnosis and targeted therapy selection. Methods: A total of 151 FFPE tumor tissue samples from patients with CCA underwent comprehensive molecular profiling using a CE IVD hybrid capture–based NGS assay targeting 1,021 cancer-related genes, 38 genes for clinically relevant fusions and a thorough analysis of SNVs, Indels, CNVs, MSI, and TMB. Sequencing was carried out using the Next Generation Sequencing DNBSEQ-T7 platform. Results: Analysis of the results revealed a diverse genomic landscape with clinically relevant alterations in a substantial proportion of patients. On-label actionable alterations were identified in 28% of cases, including IDH1 mutations (18%), FGFR2 fusions (7%), and BRAF V600E mutations (3%). IDH1 mutations were enriched in tumors consistent with intrahepatic cholangiocarcinoma, supporting their diagnostic utility. FGFR2 fusions involved a broad range of partners, highlighting biological heterogeneity and the value of NGS target enrichment detection. Off-label potentially actionable alterations were observed in 38% of patients, including RAS alterations (21%), homologous recombination repair gene alterations such as ARID1a, BAP1 , BRCA2 , ATM, CHEK2 , PALB2 (7%) and PIK3CA mutations (4%). Biomarkers associated with immunotherapy response included MSI-H/TMB-high tumors (3%). Overall, 17% of patients harbored alterations associated with clinical trial eligibility, while TP53 alterations were detected in 28%, reflecting underlying widespread genomic dysregulation. Conclusions: Comprehensive genomic profiling provides clinically meaningful insights into the molecular heterogeneity of cholangiocarcinoma. Broad NGS testing facilitates accurate molecular classification, supports differential diagnosis, and identifies actionable alterations relevant to targeted and biomarker-driven therapies. In summary, a percentage of 66% of patients harbored at least one clinically significant alteration. These findings support the routine implementation of comprehensive capture-based NGS panels in the clinical management of cholangiocarcinoma.

Ocular cancer and inpatient thrombotic phenotypes: Associations with retinal vascular occlusions and venous thromboembolism in the 2018-2022 National Inpatient Sample.

e23424 Background: Cancer-associated thrombosis is common, but ocular malignancy may have distinct local and systemic vascular effects. Ocular tumors and ocular radiotherapy can injure retinal microvasculature, yet population-level evidence linking ocular cancer to retinal occlusion and systemic VTE is limited. We evaluated associations between ocular cancer, venous thromboembolism (VTE), and retinal vascular occlusions. Methods: Retrospective cross-sectional analysis of 2018-2022 National Inpatient Sample (NIS) discharges (weighted U.S. estimates). Exposure was ocular cancer (ICD-10-CM C69). Outcomes were VTE (I26/I82) and retinal vascular occlusions (H34), subclassified as retinal vein occlusion (RVO) and retinal artery occlusion (RAO). Propensity-score matching balanced demographics, hospital characteristics, and comorbidity burden (Charlson Comorbidity Index, CCI). Post-match associations were estimated using negative binomial regression with log(length of stay) offset to obtain crude IRR and adjusted IRR (aIRR) with 95% confidence intervals (CI), incorporating NIS survey weights and robust standard errors. Length of stay and total charges were assessed with log-linear regression; effects are reported as percent change. Analyses were performed in Stata 18. Two-sided p < 0.05 was significant. Results: Among 33,905,592 weighted hospitalizations, 3,010 (0.009%) had ocular cancer. Matching improved balance (age standardized difference 32.1% to 4.1%). Unmatched event rates were VTE 2.79% vs 2.74% (p = 0.624), any RVO 0.158% vs 0.013% (p < 0.001), and any RAO 0.071% vs 0.021% (p = 0.155). After matching/adjustment, ocular cancer was associated with higher RVO (aIRR 12.16, 95% CI 3.49-42.34; p < 0.001) and lower VTE (aIRR 0.67, 95% CI 0.53-0.84; p < 0.001); RAO was not significant (aIRR 3.39, 95% CI 0.63-18.26; p = 0.155). RAO estimates were imprecise. In CCI-stratified analyses, RVO remained elevated in low/medium/high CCI (aIRR 8.52 [1.85-39.21], 13.45 [3.25-55.62], 11.21 [2.15-58.33]); VTE reduction was greatest in low CCI (aIRR 0.58 [0.36-0.94]). Ocular cancer hospitalizations had longer length of stay (+44.5%; coef 0.368 [0.330-0.405]) and higher charges (+126.4%; coef 0.817 [0.785-0.849]) (both p < 0.001). Conclusions: In national inpatient data, ocular cancer was strongly associated with retinal venous occlusion but lower coded VTE, diverging from typical cancer-associated thrombosis patterns. Findings are compatible with predominant local ocular venous vulnerability (tumor-related and/or treatment-related) rather than systemic hypercoagulability, but outpatient VTE and treatment exposures are not captured. Given discharge-level ascertainment and limited tumor detail; longitudinal studies incorporating subtype, stage, treatment exposure, and outpatient events are warranted.

Is the accelerator working? An updated empirical analysis of FDA accelerated approvals.

e23025 Background: Since 1992, accelerated approval (AA) has become the most common pathway for initial approval of cancer drugs. AA relies on early phase studies that use surrogate endpoints, which arrive sooner. Hence, earlier approval can be beneficial for effective drugs but increases the risk that drugs without clinical benefit enter the market. This study aims to analyze the duration from enrollment to approval for the accelerated approval pathway versus regular approval. Methods: This is a retrospective cross-sectional study that analyses of all original and updated clinical trials that led to FDA accelerated or regular approval of cancer-specific drugs from 2022 through 2024. Eligible approvals were identified through FDA notifications. Clinical trials relevant to each approval indication were identified through the corresponding package insert. Total study duration and time from first enrollment to data cutoff were the primary study outcomes. Univariate linear regression was utilized to assess outcomes and results were stratified by primary tumor type, phase of trial that led to approval, and type of drug approved. Results: In total, 142 distinct indications among 136 drugs approved for treatment of solid and hematologic malignant neoplasms were identified from 2022 through 2024. Of the 136 drugs approved, 35 received AA and 101 received regular approval. Studies receiving AA required on average 250 fewer patients per trial to report a difference in primary outcome (p<0.001). Drugs receiving AA required on average 77 more months (6.4 years) to reach data cutoff from first patient enrollment than those receiving regular approval (p=0.028). When utilizing surrogate endpoints, drugs receiving AA reached data cutoff in an average of 122 months while drugs receiving regular approval reached data cutoff in an average of 45 months (difference of 76 months, p=0.059). While not statistically significant, it was noted that AA approvals took 62 fewer months to reach approval from data cutoff. Conclusions: Our findings suggest that, among clinical trials leading to FDA approval of cancer drugs from 2022 through 2024, use of surrogate endpoints was associated with a 20-day shorter length of study, and use of the AA pathway was associated with a 15 month longer total study duration. In the context of previous analyses suggesting shortened development time when utilizing the AA pathway, this reversal in recent approvals along with the greater uncertainty regarding the clinical benefit of surrogate endpoints deserves further scrutiny.

Efficacy prediction for progression-free survival (PFS) and overall survival (OS) by genomic instability score (GIS) cutoffs in patients (pts) with advanced ovarian cancer (aOC): Post hoc results from the phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial.

5565 Background: GIS is a key component of a companion diagnostic assay for determining homologous recombination deficiency (HRD) status to identify pts with aOC who may benefit from maintenance therapy. While the standard GIS cutoff to classify tumors as homologous recombination-deficient (HRd) is ≥42, this study analyzed PRIMA final analysis data to see if a lower cutoff of ≥33 based on the VELIA/GOG-3005 trial could identify additional pts who experienced a PFS benefit with niraparib (nir) first-line maintenance (1LM) vs placebo (PBO). Methods: Pts with aOC were randomized 2:1 to nir or PBO 1LM. Tumor HRD status and GIS were assessed using the myChoice HRD test (Myriad Genetics). In pts with GIS data, tumor GIS distribution was assessed in the overall population and by HRD/ BRCA status. Investigator-assessed PFS at GIS cutoffs <33 vs ≥33 and <42 vs ≥42 was evaluated using Kaplan-Meier methods with Cox proportional hazards modeling (cutoff, 08Apr2024). Two statistical utility tests were performed for each cutoff: 1) to evaluate each cutoff’s potential to add incremental value to the explanation of pt response on top of treatment, and 2), in nir-treated pts, to assess each cutoff’s ability to predict long-term PFS (≥3 y). OS was assessed by increasing GIS cutoffs. Results: In the overall population (n=568), GIS ranged from 0 to 95, and 64.3% of pts had GIS ≥33 (GIS groups: 0 to <33, n=203; ≥33 to <42, n=67; ≥42, n=298). Of pts with BRCA mutation, 9.4% (21/223) of pts had GIS <42. Nir 1LM produced a significant PFS benefit vs PBO across all GIS cutoffs, with greater benefit observed in higher GIS groups (Table). The GIS ≥33 cutoff improved the Cox model fit vs the ≥42 (ie, explaining more PFS variability and showing more powerful association with PFS after treatment adjustment). In nir-treated pts with GIS data (n=387), the ≥33 cutoff increased sensitivity (0.8936 > 0.7872), identifying 10.6% more patients with PFS ≥3 y, but lowered specificity (0.4369 < 0.5734) vs the ≥42 cutoff. Higher GIS cutoffs were also associated with more favorable nir 1LM on OS effects (lower hazard ratios). Conclusions: In PRIMA, GIS existed along a spectrum, and nir 1LM resulted in a PFS benefit vs PBO across all GIS cutoffs. Pts with higher GIS experienced greater PFS benefit than pts with lower GIS. The GIS ≥33 cutoff identified more long-term PFS responders than the GIS ≥42 cutoff. Results suggest that GIS cutoffs of ≥33 used for HRd status determination may optimize identification of pts with aOC who may benefit from nir 1LM. Clinical trial information: NCT02655016 . Tumor GIS Investigator-assessed PFS <33 ≥33 <42 ≥42 Nir vs PBO, n 133 vs 65 283 vs 141 169 vs 80 247 vs 126 Hazard ratio (95% CI) a 0.69 (0.50–0.96) 0.54 (0.42–0.68) 0.67 (0.50–0.89) 0.51 (0.40–0.66) P value 0.026 <0.001 0.007 <0.001 a Stratified Cox proportional hazards model. Pts with GIS data included.

Global validation of a brain cancer liquid biopsy.

2052 Background: Delayed diagnosis of brain cancer leads to approximately two-thirds of patients being identified only after presentation to the emergency department with advanced symptoms or established neurological deficits. Implementation of a simple liquid biopsy test as a rule-out test prior to confirmatory imaging, could facilitate earlier and more efficient triage of patients presenting with non-specific symptoms suggestive of brain cancer, enabling prioritization for those most at-risk and accelerate diagnostic pathways. Methods: Presented here is the clinical validation of the Dxcover Brain Cancer Liquid Biopsy Platform obtained to support regulatory approvals. The multi-centre and observational ‘Early and tiMely detection of BRAin CancEr’ (‘EMBRACE’) study was conducted with prospective patient recruitment across seven sites in Europe. The target population consisted of patients with symptoms indicative of brain cancer. Test performance was assessed by comparison of the liquid biopsy result to diagnostic imaging. Furthermore, the liquid biopsy test was then independently tested on an additional clinical dataset obtained from a US patient population (n=234) as part of a CLIA laboratory validation study. Results: In the EMBRACE performance evaluation, 2554 patients were enrolled across the seven collection sites; 2324 were deemed eligible and taken forward for test assessment. There were 697 brain tumours in total, of which 395 were malignant, and 1627 non-tumour diagnoses. In the intended use population, the reported diagnostic performance was 86% sensitivity for brain cancer detection with 44% specificity, and a 99% negative predictive value (NPV). Notably, for the most prevalent and most aggressive brain cancer, glioblastoma, 86% of cases were successfully identified. Additionally, 94% of patients with central nervous system lymphoma, and 90% of brain metastases were predicted correctly as having tumours. The test has gained regulatory approval for use in the UK and in Europe, gaining UKCA and CE – IVDR certification respectively. The CLIA validation has provided additional confirmation of the clinical utility of the liquid biopsy test in the US population. Conclusions: Existing symptom-based referral pathways are ineffective for the detection of brain cancer, and there is an urgent need for new tests to help with clinical decision making. With a NPV of 99%, the Dxcover Liquid Biopsy test could aid with the efficient stratification of patients toward diagnostic imaging.

The Engage program for childhood cancer survivors: Results from a multidisciplinary, distance-delivered intervention.

1670 Background: As the growing number of childhood cancer survivors exceeds follow-up care capacity, scalable models to improve access and support self-management are needed. We evaluated the effectiveness of the ‘Engage’ survivorship program (primary outcomes: self-efficacy and health-related quality of life; HRQoL). Methods: Engage is a multidisciplinary program comprising a treatment summary; online health/lifestyle assessment; telehealth nurse consultations; multidisciplinary review; tailored survivorship recommendations for survivors and their nominated primary-care physician. Survivors treated at two Australian hospitals were eligible if diagnosed <18years, >5 years post-diagnosis, and completed treatment. Mixed-effects models examined change over time (baseline, 1-, 6-, 12-month) and differences by diagnosis (brain cancer vs other), adjusting for sex and age at diagnosis. Results: Of 138 consenting survivors 92% completed the health assessment and 89.1% completed the whole program (n=123). Median age was 24 years; median time since diagnosis was 15 years; 28% lived in rural/remote/regional areas; and 53% were brain cancer survivors. Program acceptability was high, with >80% of survivorsreporting Engage was helpful, improved knowledge and confidence, and was easy to access. Health-related self-efficacy improved over 12 months (χ²(3)=146.52, p<.001 ), with no evidence of differences in change between diagnostic groups (time × group; p=.97 ). HRQoL (EQ-5D index) improved modestly by 12 months (0.77 to 0.82; p=.011 ); brain cancer survivors reported lower baseline scores, with similar patterns of change over time. Satisfaction with care improved over time (χ²=35.59, p<.001 ), with higher satisfaction among non-brain cancer survivors (χ²=4.03, p=.045 ) but not over time (time×group p=.75 ). Among health behaviours, alcohol consumption decreased over time (χ²=16.20, p=001) and was higher overall among non-brain survivors (χ²=5.97, p=.015), with no time×group interaction ( p=.94 ). Adherence to personalised healthcare recommendations >50%, with greater adherence if discussed briefly during a follow-up nurse consult. Conclusions: Engage was associated with sustained improvements in survivors’ self-efficacy and satisfaction with care and modest improvements in HRQoL at 12-months follow-up. Similar trajectories across diagnosis groups suggest telehealth survivorship models can also support survivors with higher risk profiles (e.g., brain cancer survivors). Clinical trial information: ACTRN12621000590864.

A compact triple wideband mimo antenna for microwave, ku, and mm-wave band applications of 5g wireless communication

This work introduces a compact triple wideband Multiple-Input Multiple-Output (MIMO) antenna specifically designed for 5G applications. The antenna was designed simply by integrating three structures, each optimally nominated to operate within a specific frequency band. Subsequently, the antenna’s bandwidth was enhanced by incorporating a slot on the front side and an L-shaped structure on the rear side. The compact dimension of the antenna is about 37.5 × 37.5 × 1.6 mm 3 , corresponding to an electrical size of 0.375λ × 0.375λ × 0.016λ at 3 GHz. The antenna is fabricated and measured. Measurement results reveal that the developed antenna shows a fractional bandwidth of about 90.91% (5 GHz), 39.9% (6.6 GHz) and 20.4% (5 GHz) (Simulated: 101.7(40.6 GHz)) in the Sub-6 gigahertz, Ku and mm-Wave bands, respectively for |S11| < - 10dB. The proposed antenna achieves measured peak gains of 5 dBi and simulated gains of 5.5 dBi, and 10.1 dBi for the Sub-6, Ku, and mm-Wave bands, respectively for |S11| < -10dB. It has excellent diversity performance, with envelope correlation coefficients (ECC) of less than 0.06, 0.002 and 0.002 for Sub-6, Ku and mm-Wave bands respectively and diversity gains (DG) greater than 9.68, 9.99 and 9.99 for the Sub-6, Ku and mm-Wave bands respectively. Good TARC values are observed at 90-degree phase for all bands. In addition, the accepted simulated CCL values are observed for all bands. Also, the simulated and the measured MEG lies within −3 dB to −4.3 dB for all bands. Moreover, the radiation patterns in the H-plane of all bands are like omnidirectional patterns and in the E plane the antenna exhibits monopole like radiation patterns for the Sub 6 and Ku bands. The versatile multiband operation makes the designed antenna a reliable solution for advanced wireless communication systems.

A High‐Metal‐Content 2D Conjugated Metal‐Organic Framework With a Bis‐Salphen Architecture for Dendrite‐Free Sodium Metal Anodes

ABSTRACT Two‐dimensional conjugated metal‐organic frameworks (2D c ‐MOFs) are promising candidates for electrochemical applications. However, their performance is frequently constrained by conventional designs that utilize large planar conjugated ligands. Such architectures not only complicate synthetic routes but also inherently restrict the density of metal nodes, thereby limiting the availability of ion‐binding sites and impairing their efficacy in interfacial regulation. To address these challenges, we present a ligand design strategy based on a non‐planar bis‐Salphen ligand, which incorporates multiple inner N 2 O 2 coordination pockets and peripheral catechol groups. Coordination with Zn 2+ ions yields a new 2D Zn‐BSP‐MOF, wherein the ligand undergoes in situ Scholl cyclodehydrogenation during synthesis, resulting in a fully conjugated planar structure. When employed as an artificial interlayer for sodium‐less metal anodes, Zn‐BSP‐MOF exploits its high density of uniform metal‐based binding sites to guide homogeneous sodium nucleation and suppress dendrite growth. Notably, symmetric cells demonstrate outstanding stability, operating for over 1800 h at 0.05 mA cm −2 and over 800 h at 0.1 mA cm −2 . Full cells paired with a Na 3 V 2 (PO 4 ) 3 cathode deliver a high reversible capacity of 104.8 mAh g −1 after 400 cycles at 1 C, with 96.8% capacity retention.

Plantain pseudostem derived activated carbon decorated zinc oxide nanoflakes for Methyl violet 10B degradation and electrochemical applications

Mechanically Induced Adaptive Self‐Growing Protein Hydrogel

ABSTRACT Living tissues strengthen under repeated mechanical loading, yet replicating such adaptive growth in synthetic materials remains a formidable challenge. Here, we report a protein‐based hydrogel that undergoes mechanochemically induced self‐growth, autonomously reinforcing its baseline mechanical properties under applied stress. This strategy harnesses the copper‐storage protein Csp1, whose force‐regulated unfolding releases Cu(I) that catalyzes in situ azide–alkyne cycloaddition, generating secondary crosslinks under mechanical load. Upon unloading, Csp1 refolds and re‐sequesters Cu(I), halting catalysis and restoring growth capacity. This mechano‐catalytic feedback loop enables stress‐ and time‐dependent self‐reinforcement within a closed system, without external monomer supply. The hydrogel exhibits programmable mechanical memory via leveraging Cu(I) homeostasis in cyclic growth‐pause‐growth transitions. By coupling force‐dependent protein conformational dynamics with catalytic activity, this strategy establishes a generalizable mechanochemical framework for designing self‐adapting biomaterials whose structure and function evolve under mechanical stimulation.