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Efficacy and safety profiles of CDK4/6 inhibitor in patients with hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+/HER2−) advanced breast cancer (ABC) from the high-altitude versus low-altitude regions: A multi-center retrospective study.
e13033 Background: Hypoxia in the high-altitude regions may alter the pharmacokinetic properties of anti-tumor drugs, including CDK4/6 inhibitors (CDK4/6i). CDK4/6i represents the optimal first-line (1L) treatment for hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). The study is amied to assess clinical efficacy and safety profiles of CDK4/6i from first-line (1L) to third-line (3L) in patients with HR+/HER2- ABC from high-altitude versus low-altitude regions. Methods: Breast cancer patients who received CDK4/6i were enrolled from four cancer centers in China, including National Cancer Center (NCC), Chinese PLA General Hospital, and Peking University Cancer Hospital & Institute, and Qinghai University Affiliated Hospital. Suvival benefits and adverse events (AEs) were compared between high-altitude and low-altitude groups. Survival differences were analyzed via the Kaplan-Meier method and the log-rank test. Results: A total of 401 patients were eligible for the study, involving 294 from the low-altitude group, and 107 from the high-altitude group. In the 1L, objective response rate (ORR, 23.7% versus 5.3%, p=0.01), clinical benefit rate (CBR, 88.1% versus 57.9%, p<0.0001) and median progression-free survival (PFS, 42.1 months versus 15.2 months, p=0.001) in the low-altitude group were superior to high-altitude group. In the second-line treatment, CBR in the low-altitude group was higher (87.5% versus 48.0%, p=5.3E−4). ORR (20.8% versus 4.0%, p = 0.08) and PFS (15.8 months versus 8.2 months, p=0.11) were not significantly different. In the 3L settings, no significance was observed in PFS (5.2 months versus 5.8 months, p=0.45), ORR (16.5% versus 21.1%, p=0.74), and CBR (47.1% versus 47.4%, p=1). The most common AE was leukopenia (79.3%). The incidence of anemia (43.0% versus 29.6%, p=0.02) and thrombocytopenia (30.8% versus 20.4%, p=0.03) occurred more frequently in the high-altitude group. Conclusions: Patients with HR+/HER2- ABC in the high-altitude region developed inferior survival outcomes and individual tolerance to CDK4/6i, which might provide insights for optimizing the management of CDK4/6i in Chinese patients with HR+/HER2- ABC.
Long-term mortality trends of cervical cancer among younger and middle-aged women in the United States.
e17504 Background: Despite increasing human papillomavirus (HPV) immunization rates, the incidence of cervical cancer has declined disappointingly slowly in the United States (US). In this retrospective study, we aimed to analyze temporal trends, geographic variations, and disparities among younger and middle-aged women in the US. Methods: Using the CDC WONDER database for women aged 25-64 years, we analyzed age-adjusted and crude mortality rates (AAMRs and CMRs) per 100,000 for cervical cancer (ICD-10: C53) by year, race/ethnicity, and geography. Joinpoint regression (version 5.4) estimated average annual percentage change (AAPC) and annual percentage change (APC) with 95% confidence interval (CIs). Results: From 1999 to 2023, cervical cancer caused 69,631 deaths among younger and middle-aged women, most occurring at the Decedent's home. The overall AAMR slightly declined from 3.79 in 1999 to 3.00 in 2023 (AAPC: -0.99; 95% CI: -1.77 to -0.20; p=0.014), with the most significant decrease between 1999 and 2004 (APC: -3.02, 95% CI: -4.18 to -1.85; p<0.001). Women aged 45-64 years had the highest CMR with an annual decrease of -3.75% (p<0.001). Regarding racial disparities, Non-Hispanic (NH) Blacks or African Americans had the greatest AAMR with the fastest decrease at -5.05% (p<0.001), while NH Asians or Pacific islanders had the lowest AAMR. Regionally, the South showed the highest AAMR, while the Northeast showed the lowest, although the decrease was steeper in the Northeast at -1.83% (p < 0.001). Rural regions consistently outperformed urban areas, although urban locations showed a rapid improvement (AAPC: -1.00 vs -0.15). Conclusions: While cervical cancer mortality has been decreasing since 1999, not all demographic groups have experienced the same rates of decline, and disparities in outcomes remain prevalent. Vulnerable subgroups may benefit and achieve favorable outcomes from targeted treatment strategies and equitable healthcare access. Deaths and age-adjusted mortality rates (AAMRs) per 100,000 for trends related to cervical cancer among younger and middle-aged women in the US, 1999 to 2023. Variable Deaths AAMR (95%CI)1999 AAMR (95% CI)2023 Overall 69,631 3.79(3.65 to 3.93) 3.00(2.88 to 3.11) NH Blacks 13,125 6.37(5.83 to 6.91) 1.99(1.80 to 2.18) NH Asians 2,684 2.91(2.31 to 3.61) 1.04(0.86 to 1.23) South 3,509 4.21(3.96 to 4.46) 3.71(3.51 to 3.92) Northeast 10,720 3.70(3.39 to 4.02) 2.17(1.93 to 2.41) Rural 10,720 4.54(4.15 to 4.93) (2020)4.22(3.83 to 4.61) Urban 5,474 3.68(3.53 to 3.84) 3.06(2.93 to 3.18)
Asciminib in newly diagnosed Philadelphia chromosom–positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP): A retrospective chart review study in the US.
e23076 Background: Asciminib, the first BCR:ABL1 inhibitor specifically targeting the ABL myristoyl pocket, received US FDA approval in October 2024 for the treatment of adults with newly diagnosed Ph+ CML-CP based on the Phase 3 ASC4FIRST trial (NCT04971226). Asciminib was initially approved by the US FDA in October 2021. This is the first study to assess real-world clinical outcomes of patients treated with asciminib as first-line (1L) for CML-CP in US clinical practice. Methods: This retrospective, physician panel-based chart review included adult patients with CML-CP without T315I mutation who initiated asciminib as 1L (index date) between January and October 2024. De-identified data were contributed by experienced US hematologists and oncologists from community and academic centers using an online case report form between June and September 2025. Time to treatment discontinuation and time to molecular response, specifically BCR:ABL1 ≤1% (MR2 or better), ≤0.1% (MR3 or better) and ≤0.01% (MR4 or better), were assessed using Kaplan–Meier methods. Results: Overall, 30 physicians (53.3% academic, 46.7% community) from all US regions (33.3% Midwest, 30.0% South, 20.0% Northeast, 16.7% West) provided 98 charts for patients with CML-CP who initiated asciminib as 1L (Table). Most started with 80 mg daily dose (51.0% 80 mg QD, 33.7% 40 mg BID), and 13.3% initiated low dose asciminib (40 mg QD). Median follow-up period was 51.3 weeks (range: 28.1, 81.1). By 48 weeks post-asciminib initiation, the cumulative probability of achieving MR2 was 91.0% (95% CI: 84.1, 95.7; median 17.0 weeks), MR3 was 70.4% (95% CI: 60.6, 79.7; median 32.1 weeks), and MR4 was 42.6% (95% CI: 32.9, 53.9; median not reached). Cumulative probability of asciminib discontinuation by 48 weeks post-index was 7.3% (95% CI: 3.5, 14.7). Two patients discontinued asciminib due to resistance, and none due to adverse events. Cardiovascular-related adverse events were uncommon (hypertension: 4.1%, heart failure: 3.1%, QTC prolongation: 2.0%, cardiac arrhythmias: 1.0%, myocardial infarction: 1.0%). Progression to accelerated phase or blast crisis, or death was not observed. Conclusions: This first, diverse real-world cohort of newly diagnosed patients with CML-CP treated with asciminib demonstrated efficacy outcomes, including deep molecular responses and discontinuation rates consistent with ASC4FIRST. These findings support asciminib’s favorable risk-benefit profile and its role as a standard of care in 1L for CML management in US clinical practice. Patient characteristics. Median or % Age 56 Female 46.9 White / Black / Hispanic / Other 60.2 / 16.3 / 17.3 / 6.1 Sokal low / intermediate / high / unknown 17.3 / 67.3 / 13.3 / 2.0 ECOG 0 / 1 / ≥2 28.6 / 60.2 / 11.2 Hypertension / COPD / Diabetes 30.6 / 12.2 / 7.1 Framingham risk score low / intermediate / high / unknown 31.6 / 51.4 / 6.1 / 8.2
Recognition and management patterns of cachexia in patients with pancreatic adenocarcinoma in a safety net hospital.
e24079 Background: Cachexia is a metabolic syndrome marked by disrupted protein and energy balance, affecting up to 80% of patients with advanced cancer. Muscle loss and weakness reduce performance status, quality of life, and treatment tolerance. Despite contributing to ~20% of cancer deaths, cachexia remains under-diagnosed and under-treated. Methods: We performed a retrospective review of adults aged ≥18 years treated at Harbor UCLA, a safety net county hospital, from 2015-2025 with biopsy-confirmed pancreatic adenocarcinoma. Cachexia was defined as BMI < 20 kg/m2 and/or ≥5% weight loss over 6 months. Collected variables included patient demographics, stage, initial treatment, BMI at diagnosis and last follow-up, baseline albumin, cachexia status and documentation, cachexia-directed medications, and nutrition or palliative care involvement. We analyzed the prevalence of cancer cachexia, referral patterns for this condition, as well as treatments utilized. Analysis was conducted through descriptive statistics. Results: 66 patients were included in this study. Median age at diagnosis was 60 years; 51.5% were male. The cohort was 54.5% Hispanic, 27.3% Black, 9% Asian, 4.5% Caucasian, 3% other/unknown, and 1.5% American Indian. Patients were 24.2% stage 1, 28.8% stage 2, 28.8% stage 3, and 18% stage 4. FOLFIRINOX (54.5%) and Gemcitabine plus Protein-Bound Paclitaxel (25.8%) were the two most common chemotherapy regimens. 25.8% received radiation, while 42.4% of patients underwent surgery. 35.7% of patients who originally were candidates for surgery ultimately did not undergo planned surgical resection. 63.6% of patients had progression of disease. Mean BMI at diagnosis was 25.2, while mean final BMI declined to 21.45. Mean albumin at diagnosis was 3.35. Cachexia criteria were met by 89.4% of patients, but only 16.7% had documented diagnoses. 48.5% of patients were seen by palliative care, and 45.5% of patients were seen by a dietician. Cachexia-directed medications were given to 23.7% of patients. 11.8% of patients received Dronabinol, 10.2% of patients received Mirtazapine, and 1 patient received Olanzapine. Conclusions: There is a dearth of studies that describe incidence and management patterns of cancer-related cachexia in safety net populations. Cachexia was highly prevalent yet infrequently diagnosed or documented at our institution. A minority of patients with cachexia received pharmaceutical management, while less than half were evaluated by palliative care or nutrition. One third of patients were unable to undergo planned surgery due to factors including disease progression and cachexia. Improved recognition and management strategies of cachexia are needed.
Dynamics of circulating monomeric C-reactive protein (mCRP) to predict outcomes with first-line alternating oxaliplatin-based chemotherapy and nivolumab in metastatic microsatellite-stable (MSS) colorectal cancer (CRC).
3606 Background: Elevated CRP levels at CRC diagnosis are consistently associated with poor outcomes, suggesting a tumor-promoting and potentially immuno-suppressive inflammatory state. The clinically assessed CRP is a pentameric protein that can dissociate to mCRP, an isoform with pro-inflammatory effects on innate immune responses. The randomized METIMMOX trial (NCT03388190) evaluated potentially immunogenic short-course oxaliplatin-based chemotherapy (FLOX) alternating with nivolumab in previously untreated, unresectable metastatic MSS CRC. We investigated whether oxaliplatin-induced immunogenicity is measurable as an early change in circulating mCRP and may identify patients more likely to derive clinical benefit from sequential nivolumab. Methods: Patients were randomly assigned to the control group of FLOX (oxaliplatin, 5-fluorouracil, folinic acid) Q2W or the experimental group of alternating 2 cycles each of FLOX Q2W and nivolumab Q2W with prespecified break periods. The primary endpoint was progression-free survival (PFS). This post hoc analysis included 29 patients from the experimental group, of whom 28 had paired mCRP and clinical CRP measurements from baseline (Pre) and post second FLOX cycle (Post) timepoints. CRP was measured by standard immunoturbidimetry. Plasma mCRP was separated from CRP by 100-kDa filtration and quantified by targeted nano LC-timsTOF Pro mass spectrometry with AQUA standards. CRP at the reference limit 5.0 mg/L and mCRP at the median value 45 ng/mL were used as cutoff values. Changes from Pre to Post were denoted ΔmCRP and ΔCRP and categorized as ³0 (stable/increase) and < 0 (decrease). Results: Low Pre and low Post CRP were associated with prolonged PFS (log-rank p = 0.080 and p = 0. 002, respectively), while ΔCRP showed no association (log-rank p = 0.57). By contrast, a significant association was observed for ΔmCRP (log-rank p = 0.015), where median PFS was longer among the ΔmCRP ≥0 population (16.4 months [95% CI 8.8-23.9]; n = 15) versus the ΔmCRP < 0 population (9.2 months [95% CI 3.6-14.8]; n = 13). Notably, patients with the combination ΔCRP < 0 and ΔmCRP ≥0 ( n = 8) had an undefined median PFS (≥41.6 months) at data cutoff, compared to median PFS 9.2 months (95% CI 1.4-16.9; n = 20) for all other patients (log-rank p = 0.022). Conclusions: Patients with metastatic MSS CRC who exhibited an increase in mCRP and decrease in clinical CRP following the initial 2 chemotherapy cycles of first-line oxaliplatin-based chemotherapy alternating with nivolumab had markedly prolonged PFS. Moreover, increased PFS was observed alongside increased circulating mCRP regardless of change in CRP. These data suggest an early increase in mCRP may be an indicator of immunotherapy-associated efficacy. Clinical trial information: NCT03388190 .
Clinicopathological characteristics and survival outcomes of liver cancer in a tertiary oncology center.
e16187 Background: Liver cancer is an aggressive malignancy with poor overall survival, particularly when diagnosed at advanced stages. Although advances in systemic therapies have improved outcomes in selected populations, real-world data on disease presentation, treatment utilization, and survival outcomes remain limited in sub-Saharan Africa (SSA). This study evaluated clinicopathological characteristics, treatment patterns, and survival outcomes among patients with liver cancer managed in a tertiary oncology centre. Methods: We conducted a retrospective analysis of patients with liver cancer managed at the Medserve-LUTH Cancer Centre, Lagos, Nigeria, between June 2019 and May 2024. Descriptive statistics were used to summarize patient characteristics. Survival outcomes were analyzed using the Kaplan-Meier method, with p < 0.05 considered statistically significant. Results: Among 68 patients, the mean age at diagnosis was 53 ± 13.9 years (range 25-85), and 70.6% were male. Hepatocellular carcinoma was the most common histological subtype (86.8%). The most frequent presenting symptoms were abdominal pain (45.6%), weight loss (35.3%), jaundice (13.2%), fatigue (13.2%), and hepatomegaly (10.3%). A history of smoking was reported in 8.8%, while 22.1% reported alcohol use. Family history of cancer was documented in 2.9% of patients. Comorbidities were present in 50% of patients, including hypertension (17.6%), diabetes (10.3%), and peptic ulcer disease (5.9%). Hepatitis B and C infections were present in 17.6% and 2.9% of patients, respectively. Metastatic disease commonly involved the bone (23.5%), lung (16.2%), and demonstrated intrahepatic spread (13.2%). Treatment modalities included surgery (2.9%), chemotherapy (13.2%), and radiotherapy (11.8%). The one-year survival rate was 13.1%. Kaplan-Meier analysis showed a mean survival time of 6.17 ± 7.83 months (95% CI: 4.63-7.71) and median survival time of 3.93 ± 5.08 months (95% CI: 2.94-4.93). Survival did not differ significantly by age, metastatic status, comorbidity burden, or receipt of radiotherapy. Conclusions: Real-world outcomes for patients with liver cancer remain poor, with a short median survival and low one-year survival rates. Late presentation, high comorbidity burden, and limited access to effective therapies likely contribute to these outcomes. Strengthening early detection strategies, improving linkage to care, and expanding access to effective systemic and locoregional treatments are essential to improving survival in patients with liver cancer in SSA.
Geographic access to ONC201 (dordaviprone) trials for pediatric diffuse midline glioma in the United States: County travel burden and social vulnerability gradients.
e14054 Background: ONC201 (dordaviprone) is currently under study for H3 K27M–mutant midline gliomas including pediatric diffuse midline glioma (DMG). We quantified county travel burden to ONC201 study sites and assessed whether access to clinical trials is worse in socioeconomically vulnerable counties and highlighted the need for more equitable access to trial sites across the United States. Methods: From a ClinicalTrials.gov extract, we identified ONC201 studies with U.S. locations (N=5) and extracted site latitude/longitude; sites were de-duplicated to unique coordinates. Cohorts were (1) pediatric-only DMG interventional trial NCT03416530 and (2) pediatric-eligible ONC201 (interventional plus expanded access). For each county centroid (Census Gazetteer), we calculated haversine distance to the nearest site and summarized thresholds (≤100, ≤200 miles). Counties were linked to 2022 CDC/ATSDR SVI (RPL_THEMES) and categorized into national quintiles; population-weighted metrics used county population. Results: NCT03416530 had 8 U.S. locations across 8 states. Median distance to the nearest pediatric-only site was 279 miles (IQR 169–489); 11.0% and 32.2% of counties were within 100 and 200 miles, respectively. The pediatric-eligible cohort included 54 locations (median 109 miles; 45.9% within 100 miles; 80.9% within 200 miles). Access showed a deprivation gradient: median distance increased from 100.1 miles (SVI Q1) to 124.7 miles (SVI Q5), and population-weighted proximity within 100 miles declined from 76.8% to 71.8%. High-vulnerability counties had lower odds of being within 50 miles (SVI Q5 vs Q1 OR 0.30; p<0.001). In SVI Q5, 10.8% (~9.5M of 88.2M) lived >200 miles from the nearest pediatric-eligible site. That high-burden SVI Q5 population was concentrated in the South (59.9%) and West (38.8%), driven by TX (32.1%), NV (23.8%), TN (11.5%), NM (9.5%), and AR (6.0%). Conclusions: Pediatric-only ONC201 DMG trial access is sparse, and socioeconomic vulnerability is associated with reduced proximity even when expanded access sites are included. Regional satellite activation, travel support, and telemedicine-enabled screening may reduce inequities for families affected by pediatric DMG. Our study highlights the emerging need for policy changes that would incentive clinical trial sites to expand access into socio-economically deprived regions for this rare, aggressive pediatric disease.
Real-world outcomes and recurrence risk factors of liver transplantation for permanently unresectable colorectal liver metastases following the TransMet trial.
3589 Background: Following the TRANSMET trial that demonstrated an overall survival (OS) benefit of liver transplantation (LT) over chemotherapy (CT) alone for selected patients with permanently unresectable colorectal liver metastases (uCRLM), the program of LT has continued in France with the same eligibility criteria, independent validation and graft allocation policy. We assessed the real-world oncological outcomes and prognostic factors for post-LT recurrence-free survival (RFS) in the whole cohort. Methods: This nation-wide analysis pooled both patients transplanted in TransMet (Trial cohort) and those after trial closure (Extension cohort). OS and RFS were evaluated in each cohort. Multivariable Cox models for RFS using sensitivity analyses including forced cohort adjustment and bootstrap resampling were performed. Results: A total of 87 patients underwent LT (37 Trial cohort; 50 Extension cohort). Baseline characteristics at CRLM diagnosis were comparable. At LT, patients in the Extension cohort received significantly fewer CT cycles (≥24 cycles, 16% vs 41%, p=0.01) and showed higher rate of partial response (94% vs 57%, p < 0.001) after first-line CT. At time of LT, tumor burden, RECIST status and tumor markers were similar. Median follow-up was shorter in the Extension cohort (16 vs 57 months). No significant differences in OS and RFS were observed between extension and trial cohorts (30-months OS 89% vs 81%; 30-months RFS 47% vs 39%, respectively). In univariable analysis, risk factors of RFS included ≥2 CT lines, ≥24 CT cycles before LT, CEA at LT > 5 ng/mL, progression on CT and interval from primary tumor surgery >2 years. In multivariable Cox analysis, ≥2 lines or >24 cycles before LT (HR 2.90, 95% CI 1.32–6.36; p<0.01) and CEA at LT >5 ng/mL (HR 2.26, 95% CI 1.18–4.33; p=0.01) remained independently associated with RFS, adjusted on interval from primary tumor surgery. Bootstrap resampling (2,000 iterations) highlighted these results in 82% and 67% of models, respectively. Conclusions: LT for uCRLM gives good and reproducible oncological outcomes across trial and extension cohorts. This exploratory analysis supports that RFS is impaired by a prolonged pre-transplant chemotherapy (≥ 2 lines or ≥ 24 cycles) and improved by a good biological response (normalization of CEA), supporting considering LT in a multidisciplinary setting as soon as definitive unresectability is established.
Efficacy and safety of XNW27011, a Claudin-18.2 targeted (CLDN18.2) ADC, in advanced pancreatic ductal adenocarcinoma: A phase 2 study.
3039 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a historically poor prognosis, the median overall survival (mOS) for PDAC patients (pts) who received ≥ 1 prior lines of standard treatments is only 6.2 to 7.4 months(mos). XNW27011 is a novel and potent Topoisomerase inhibitor (TOP1i)-based ADC targeting CLDN18.2. In preclinical studies, XNW27011 demonstrated antitumor activities in PDAC, supporting its progression into clinical development. Here, we report results of XNW27011 in pts with PDAC. Methods: The objectives of this phase 2 study were to evaluate the efficacy and safety of XNW27011 in PDAC, and to optimize doses for subsequent confirmatory trials. Pts with PDAC expressing CLDN18.2 (defined as ≥5% tumor cells with ≥2+ IHC staining) who had received prior systemic therapy were treated with XNW27011 at doses from 2.4 - 4.8 mg/kg, Q3W. The primary endpoint was ORR, secondary endpoints included TRAEs for safety, DCR, PFS, OS, and PK parameters. Results: As of Dec 29, 2025, a total of 48 pts had been enrolled with majority of them being enrolled in 3.0 mg/kg group. Among the 48 pts, the ECOG PS was 0 or 1, the median age was 59.0 years. 18 pts (37.5%) had received 1 prior line of systemic therapy. 22 pts (45.8%) had been treated with TOP1i. Efficacy: A total of 30 PDAC pts in the 3.0 mg/kg dose group were evaluable for efficacy. The ORR and DCR was 26.7% and 83.3%, respectively. mPFS and mOS was 4.1 and 10.0 mos, respectively. Among the 13 pts who had received only one prior line of therapy, the ORR was 46.2% and the DCR was 100.0%, mPFS was 4.4 mos, OS was not mature yet. However, the current mOS was 10.1 mos with the median follow-up of 8.1 mos. Detailed efficacy data are presented in the table. Among the pts who were previously treated with TOP1i, the median follow-up was 7.9 mos, the mPFS and mOS were 5.2 and 10.0 mos, respectively. Safety: Among the 48 PDAC pts, the incidence of treatment-related adverse events (TRAEs) was100.0%. The incidence of Grade ≥3 TRAEs and serious TRAEs were 77.1% and 58.3%, respectively. 35.4% and 6.3% of the TRAEs led to dose reduction and discontinuation, respectively. The most common TRAEs included nausea (77.1%), vomiting (64.6%), decreased appetite (64.6%) and anemia (62.5%). Pharmacokinetics: At doses of 0.6-6.0 mg/kg in patients with solid tumors including PDAC, the XNW27011 exposure (C max and AUC 0-∞ ) increased in an approximately dose proportional manner with a half-life of 5~7 days. Across all dose levels, circulating payload blood concentrations were low with 3.3% ADA positive rate. Conclusions: XNW27011 showed a manageable safety profile and encouraging survival outcome in pts with PDAC expressing CLDN 18.2, supporting its further clinical development as a promising therapeutic option for patients with PDAC expressing CLDN 18.2. Clinical trial information: NCT06792435 .
PFS2 outcomes by prior therapy from DREAMM-8: A phase 3 study assessing belantamab mafodotin (belamaf), pomalidomide, and dexamethasone (BPd) vs pomalidomide, bortezomib, and dexamethasone (PVd) in patients (pts) with relapsed/refractory multiple myeloma (RRMM).
7566 Background: B-cell maturation antigen (BCMA)–directed therapies have transformed the treatment landscape in RRMM. Belamaf, a BCMA-targeting antibody-drug conjugate, in combination with Pd significantly improved progression-free survival (PFS) vs PVd (hazard ratio [HR], 0.52; 95% CI, 0.37-0.73; P <0.001) in pts with RRMM in DREAMM-8 (median follow-up, 22 mo). This PFS benefit was maintained with extended follow-up (HR, 0.49; 95% CI, 0.36-0.67; median follow-up 36 mo); median PFS2 also favored BPd vs PVd (47.1 vs 21.7 mo, respectively; HR, 0.52; 95% CI, 0.38-0.70), indicating sustained clinical benefit over time. We report PFS2 outcomes from DREAMM-8 in subgroups based on prior therapy to further understand the long-term impact of BPd and inform treatment sequencing. Methods: DREAMM-8 (NCT04484623) is a phase 3, randomized, open-label study evaluating BPd vs PVd in pts with RRMM with ≥1 prior line of therapy including lenalidomide (LEN). Pts could not have received prior BMCA-targeted therapy. PFS2 was defined as time from randomization to disease progression after initiation of subsequent antimyeloma therapy or death. PFS2 was assessed based on prior-treatment subgroups. Results: In the BPd arm (DCO: Jul 7, 2025; median follow-up, 36 mo), PFS2 benefit was maintained in all subgroups, including pts who were LEN refractory and anti-CD38 exposed/refractory. In LEN-refractory pts, BPd treatment led to almost a 3-fold median PFS2 improvement vs PVd (41.7 vs 15.0 mo). A total of 56/155 pts (36%) in the BPd arm and 93/147 (63%) in the PVd arm received any first subsequent therapy (FST) at data cutoff. Across both arms, 36% of pts received steroids, 28% received anti-CD38 therapies (>50% of pts with any subsequent therapy in each arm), and 23% received proteasome inhibitors as FST. A total of 21 pts (7%) received novel therapies (BPd, n=6 [4%]; PVd, n=15 [10%]) as FST, including BCMA-targeted bispecific antibodies (bsAbs), non-BCMA bsAbs, CELMoDs, venetoclax, and belamaf. Improved median PFS2 was observed in patients who had novel therapies as FST (n=21) vs non-novel agents (n=128) (26.0 vs 20.1 mo; HR, 0.61; 95% CI, 0.34-1.09). Conclusions: BCMA-directed therapy, BPd, resulted in improved PFS2 outcomes vs PVd, demonstrating sustained clinical benefit beyond initial belamaf therapy. This benefit was seen regardless of prior treatment, with LEN-refractory pts experiencing almost a 3-fold PFS2 benefit, and despite a higher proportion of pts receiving novel therapies as FST in the PVd arm. PFS2 benefit with high use of subsequent anti-CD38 agents supports sequencing of belamaf combinations early in the treatment paradigm prior to anti-CD38 agents.
Single-cell analysis and functional profiling of galectin-3 in the tumor immune microenvironment in transformed follicular lymphoma.
7055 Background: Histological transformation of follicular lymphoma (tFL) represents an aggressive subtype characterized by a complex and immunosuppressive tumor immune microenvironment (TIME). Therefore, it is urgent to investigate the characteristics of TIME and develop more effective immunotherapy strategies for tFL patients. Methods: Using single-cell RNA sequencing, a high-resolution landscape of the entire TIME ecosystem of follicular lymphoma (FL) and tFL patients is depicted. Findings were validated by multiplex immunofluorescence (mIF) staining, in vitro assays, and a mouse model. Results: Compared to FL patients, tFL patients exhibited a higher proportion of exhausted CD8+T cells expressing checkpoint receptors such as LAG3, CTLA4, PD-1, and HAVCR2. Notably, Galectin-3 expression was acquired by tumor cells after transformation, leading to enhanced Galectin-3–LAG3 interactions with CD8⁺ T cells, as confirmed by mIF staining. In co-culture experiments, Galectin-3-overexpressing tumor cells impaired CD8⁺ T cell proliferation and cytotoxicity, inducing an exhausted phenotype. Treatment with the Galectin-3 inhibitor GB1107 rescued T cell function. Similar T cell dysfunction and GB1107 response were observed in Galectin-3-overexpressing mouse xenograft model. Additionally, we identified an accumulation of MDSC-like monocytes and M2-like macrophages in tFL patients, further contributing to immune suppression. Conclusions: Galectin-3 drives T cell exhaustion and reshapes the immune microenvironment in tFL patients, promoting immune evasion and disease progression. Targeting Galectin-3 may represent a promising immunotherapeutic strategy for tFL patients.
Clinical utility of DNA and RNA next-generation sequencing (NGS) for accurate diagnosis (Dx) and sub-classification of bone and soft tissue tumors (BST).
e23521 Background: BST account for only 1-2% of adult cancers but encompass >100 distinct entities with diverse histology, genomics, prognosis, and clinical management. This rarity and heterogeneity make accurate dx and sub-classification challenging. We evaluated the clinical utility of concurrent DNA-/RNA-NGS for dx of BST. Methods: DNA/RNA co-extracted from tumor tissue were profiled with hybrid-capture NGS assays FoundationOne CDx (DNA), which interrogates alterations in 324 genes, and FoundationOne RNA which detects fusions in 318 genes. Fusions were filtered using a list of known dx fusions from NCCN guidelines, and all cases underwent central review by a board-certified pathologist. Results: Between Jun-Dec 2024, 270 bone (8%, n=22) and soft tissue (92%, n=248) tumors from unique patients underwent parallel DNA-/RNA-NGS during routine clinical care. Reportable results were obtained for both analytes in 90% of cases (n=244). The most common submitted pathology dx were sarcoma NOS (23%), GIST (12%), non-uterine leiomyosarcoma (10%), angiosarcoma (7%), and liposarcoma (5%). Dx fusions were identified in 24% (n=64) of cases, which confirmed the submitted dx in 21% (n=57), refined the classification in 2% (n=4), and corrected a misdiagnosis in 1% (n=3; Table). The most common recurrent fusions included NAB2 :: STAT6 (n=8), PAX3 :: FOXO1 (n=6), EWSR1 :: FLI1 (n=4), and SS18 :: SSX1 (n=4). Notably, 75% (43/57) of confirmed dx and 100% (7/7) of revised dx were based on fusions detected in RNA only. In addition, therapeutically targetable fusions were detected in 5 cases (2%; ALK n=2, BRAF , FGFR2 , NTRK1 ). Conclusions: Concurrent DNA-/RNA-NGS provided dx utility in 24% of BST, leading to revised diagnoses for 7 patients. Inclusive of targetable fusions, RNA-NGS added incremental value to DNA-NGS alone for 19% (51/270) of patients. These findings support a multimodal dx strategy combining morphology, immunohistochemistry, and both DNA- and RNA-NGS for accurate classification and management of BST. Reclassified BST N=7. Case Submitted Pathology Dx Dx Fusion (All RNA Only) Revised Integrated Dx Dx Corrected 1 Epithelioid Angiosarcoma YAP1 :: TFE3 Epithelioid Hemangioendothelioma 2 Uterine EndometrialStromal Sarcoma COL1A1 :: PDGFB COL1A1-PDGFB Fusion‐AssociatedUterine Fibrosarcoma 3 Atypical CellularFibrous Meningioma NAB2 :: STAT6 Solitary Fibrous Tumor Dx Refined 4 Spindle Cell Neoplasm w/ Vaguely Fibromyxoid Stroma, Differential Incl. Ossifying Fibromyxoid Tumor PRRX1 :: NCOA2 PRRX-NCOAx -Rearranged Fibroblastic Tumor 5 Undifferentiated Round Cell Sarcoma, Possible BCOR Sarcoma MGA :: NUTM1 NUTM1 -Rearranged Spindle Cell Sarcoma 6 Undifferentiated Uterine Sarcoma w/ Osteosarcomatous Component JAZF1 :: SUZ12 Uterine Endometrial Stromal Sarcoma 7 Differential Incl. MPNST, BCOR Lesion, Other Primitive Sarcoma SS18 :: SSX2 Synovial Sarcoma
Efficacy and safety analysis of intraoperative radiotherapy for soft tissue sarcoma: The largest-sample, single-center, real-world data review.
11579 Background: This study aimed to evaluate the efficacy and safety of surgery combined with intraoperative radiotherapy (IORT) versus surgery combined with postoperative adjuvant radiotherapy in the treatment of soft tissue sarcoma (STS). It sought to identify patient subgroups that derive the most benefit from IORT and to provide evidence for treatment selection. Methods: This retrospective single-center study was conducted at Tianjin Medical University Cancer Institute & Hospital between May 2021 and December 2024. A total of 420 patients with pathologically confirmed STS were initially screened. After applying strict inclusion and exclusion criteria, 252 eligible patients were enrolled and divided into two groups: 147 patients who underwent surgery combined with IORT using the INTRABEAM 600 System, and 105 patients who received surgery combined with conventional postoperative adjuvant radiotherapy. Results: After a median follow-up period of 17.2 months (range: 4.8-47.18 months), the IORT group demonstrated significantly superior outcomes. Multivariate analysis identified three independent risk factors for RFS: radiotherapy modality (IORT vs. postoperative radiotherapy, p = 0.001), primary versus recurrent tumor status (p < 0.001), and T stage (p = 0.003). The RFS in the IORT group was significantly better than in the postoperative radiotherapy group (P = 0.001). Subgroup analysis revealed that IORT was particularly advantageous for specific patient populations. Tumor size was a critical determinant: for lesions larger than 5 cm in diameter, IORT significantly improved RFS across all subgroups ( > 15 cm: p = 0.008; 10-15 cm: p = 0.008; 5-10 cm: p = 0.004). However, for tumors smaller than 5 cm, no significant difference was observed between the two treatment modalities (p = 0.874). For OS, multivariate analysis identified radiotherapy type (p = 0.01) and AJCC stage (p = 0.007) as independent risk factors. The IORT group showed a trend toward improved OS, though longer follow-up is needed for definitive conclusions. The safety analysis strongly favored IORT. The incidence of treatment-related adverse events was significantly lower in the IORT group across all categories. Conclusions: This large-sample, single-center real-world study demonstrates that surgery combined with intraoperative radiotherapy significantly prolongs recurrence-free survival and improves local control in soft tissue sarcoma patients compared to surgery combined with postoperative radiotherapy. The benefits are most pronounced in patients with primary or recurrent tumors larger than 5 cm in diameter. Additionally, IORT offers a substantially more favorable safety profile with significantly reduced rates of radiation-related adverse events.
Outcomes of inpatient (IP) systemic cancer therapy in patients (pts) with solid tumors.
e23059 Background: Administration of IP cancer therapy requires substantial resources and carries risk of toxicity. Given this, we sought to describe the pts receiving IP cancer therapy at our institution to identify areas for improvement. Methods: We performed a retrospective chart review of adult pts with solid cancer who received unplanned intravenous IP cancer therapy at an academic tertiary care hospital between April and October 2024. Pts with hematologic malignancies or preplanned cancer therapy admissions were excluded. Outcomes included 30-day readmission, receipt of subsequent cancer-directed therapy, and six-month post-discharge hospice enrollment and mortality. Results: 161 pts were included, median age was 60 years, 51% male sex, 76% had metastatic cancer, 46% White and 28% Asian race; most common cancer type was gastrointestinal (42%), and thoracic (12%). 65% of pts were on their first line of therapy. The most common reason for administration was complication of cancer requiring immediate disease control (54%). 52% died from any cause within the following 6 months including 12% (n=20) who died during the index hospitalization. Of the 87 pts receiving therapy for a cancer-related complication, 20% (n=17) died during the hospital stay. Of those (n=70) discharged alive, 33% saw palliative care prior to or during the hospitalization, 24% had an IP goals of care discussion, and 70% were full code on discharge. Further, 70% went on to receive additional cancer treatment post discharge, 41% were readmitted within 30 days, 41% transitioned to hospice within the next 6 months and 49% died from any cause with half of them dying in a subsequent hospitalization. Compared to pts who went on to receive additional cancer treatment, pts treated who did not receive further therapy after discharge were more likely to have metastatic disease (p=0.02) and poor performance status (ECOG 3–4; p=0.01). There was no difference in age or likelihood of having GI cancer or being on salvage therapy (vs front-line therapy). Conclusions: Over a six-month period, nearly one pt per day received unplanned IP cancer therapy and 20% of those who received chemotherapy for cancer-related complications did not survive index hospitalization. Functional status and disease burden preceding IP therapy for cancer-related complications were associated with no further cancer therapy upon discharge, which suggests a population who may be inappropriate for IP therapy. Standardizing criteria for IP cancer therapy could help prevent overuse of this resource-intensive treatment. Baseline characteristics. All patients (N=161) Age, median (IQR), yr 60 (23) Male sex, n (%) 82 (51) Race, n (%) WhiteAsianBlack 74 (46) 45 (28) 4 (2) Cancer type, n (%) a GI Thoracic Breast GU Head/Neck Sarcoma 67 (42) 20 (12) 10 (6) 14 (9) 15 (9) 15 (9)
Impact of DLL3 expression and tumor subtype on response to tarlatamab.
8087 Background: Tarlatamab is a DLL3-targeted bispecific T-cell engager used to treat small cell lung cancer (SCLC). SCLC subtypes can be defined by relative expression of master transcription factors (TFs). Whether subtype and DLL3 expression are associated with outcomes on tarlatamab is unknown. Methods: We analyzed all patients (pts) with SCLC, including SCLC transformed from lung adenocarcinoma, treated with tarlatamab at Memorial Sloan Kettering prior to October 2025. DLL3 expression and subtyping were determined by IHC by dedicated thoracic pathologists. Expression of subtype TFs ASCL1, NEUROD1, POU2F3, and YAP1 was assessed. “Neuroendocrine (NE)-high” was defined as any ASCL1 or NEUROD1 expression. Pts with any “neuroendocrine (NE)-low” subtype expression—POU2F3 or YAP1—were grouped for analysis. DLL3 fractional expression was dichotomized as “high” (≥50%) or “low” (0-49%). Progression-free and overall survival (PFS, OS) were analyzed with Kaplan-Meier curves and compared with the Cox proportional hazards model. Results: We identified 39 pts with SCLC treated with tarlatamab with DLL3 and/or subtyping data available. Median age was 65, 49% were women, and median prior lines of therapy was 1. DLL3 expression was available in 34 pts. Median fractional DLL3 expression was 80% and ranged from 0 to 100%. 7 pts had low expression and 27 had high expression. There were more pts with transformed SCLC in the DLL3-low group (3/7 [43%] vs 1/27 [4%], p=0.02). Among pts with response data available, response was inferior in the DLL3-low group: complete or partial response (CR or PR) in 0/7 (0%; [95% CI, 0 to 35]) vs 12/25 (48%; [95% CI, 30 to 67]); stable disease (SD) in 2/7 (29%) vs 5/25 (20%); progressive disease (PD) in 5/7 (71%) vs 8/25 (32%); p=0.049. Median PFS was 1.4 mos in DLL3-low vs 4.5 mos in DLL3-high disease (p<0.001); median OS was 4.7 mos vs not reached (p=0.001). Incidence of CRS and ICANS did not differ (5/7 [71%] in DLL3-low vs 11/29 [38%] in DLL3-high with CRS, p=0.2; 0/9 vs 3/29 [10%] with ICANS, p>0.9). 30/39 pts had subtyping data available. 28/30 pts had NE-high tumors (15/28 ASCL1+/NEUROD1+; 11/28 ASCL1+/NEUROD1-; 2/28 ASCL1-/NEUROD1+). 5/30 had subtype biomarkers of NE-low status: 4 YAP1+ and 1 POU2F3+; the 4 YAP1+ tumors also expressed ASCL1. Response rates were similar between pts with and without NE-low expression: 1/5 (20%; [95% CI, 1 to 62]) vs 11/25 (44%; [95% CI, 27 to 63]), p=0.6. PFS was also similar (mPFS 1.1 vs 2.7 mos, p=0.3). Conclusions: Low DLL3 expression was potentially associated with inferior response to tarlatamab. A contributing factor may be enrichment of transformed SCLC, which is associated with poor outcomes. We did not detect an impact of POU2F3/YAP1 expression. The majority of pts in this cohort had DLL3-high, NE-high SCLC—in line with prior studies—and they had a response rate of 48%. These data emphasize the need for more discerning predictive biomarkers for tarlatamab in an evolving landscape of treatment options.
Atrial fibrillation as a sentinel cardiovascular event in renal cell carcinoma hospitalizations: National Inpatient outcomes and rescue failure (NIS 2016–2023).
e23226 Background: Cardiovascular instability is common during renal cell carcinoma (RCC) hospitalizations, yet atrial fibrillation (AF) is often treated as incidental. This study reframes AF as a sentinel inpatient event that may identify early physiologic decompensation and worse rescue outcomes in RCC. Methods: A survey-weighted analysis of the 2016–2023 National Inpatient Sample was performed. Adult RCC hospitalizations were identified by diagnosis codes. AF phenotypes were defined as no AF, secondary AF (AF present but not the principal diagnosis), or AF-primary (AF as the principal diagnosis). Outcomes included in-hospital mortality, ICU-level care proxy (mechanical ventilation, dialysis, or shock), major complications (sepsis, acute kidney injury, respiratory failure, shock, ventilation, or dialysis), failure-to-rescue (death among admissions with major complications), length of stay (LOS), and costs/charges. Multivariable survey-weighted regression adjusted for demographics, payer, income quartile, weekend admission, admission acuity, hospital characteristics, and year. Results: Among an estimated 733,705 RCC hospitalizations nationally, AF was present in 15.6%, including 15.0% secondary AF and 0.63% AF-primary. Outcomes differed markedly by AF phenotype. Mortality was 3.31% with no AF, 6.57% with secondary AF, and 2.38% with AF-primary. ICU-level care occurred in 7.57% with no AF versus 14.47% with secondary AF (AF-primary 7.78%). Major complications occurred in 36.1% with no AF versus 56.7% with secondary AF (AF-primary 37.0%). Failure-to-rescue among admissions with major complications was 7.66% with no AF and 10.62% with secondary AF (AF-primary 5.26%). Mean LOS was longer with secondary AF (6.83 vs 4.95 days), with higher mean costs ($26,261 vs $22,489) and charges ($90,907 vs $77,612). In adjusted analyses, secondary AF was independently associated with higher mortality (aOR 1.54, 95% CI 1.43–1.66), ICU-level care (aOR 1.96, 95% CI 1.85–2.06), major complications (aOR 1.66, 95% CI 1.60–1.72), and failure-to-rescue (aOR 1.41, 95% CI 1.30–1.53), each compared with no AF. AF-primary was associated with lower adjusted mortality (aOR 0.41, 95% CI 0.26–0.67) and fewer major complications (aOR 0.53, 95% CI 0.45–0.61) versus no AF. Conclusions: In RCC hospitalizations, AF is common and heterogeneous. Secondary AF identifies a high-risk inpatient phenotype with substantially higher mortality, ICU escalation, major complications, and failure-to-rescue, consistent with AF as a sentinel marker of acute systemic stress rather than an incidental comorbidity.
The impact of language barriers on financial toxicity for Spanish-speaking patients undergoing cancer treatment.
e13504 Background: Financial toxicity refers to the economic burden experienced by patients due to medical care costs. Cancer treatment often involves surgery, chemotherapy, and radiation, resulting in high out-of-pocket expenses even for insured patients. Factors such as limited insurance coverage, job loss, and being the sole household income provider further exacerbate this burden. Language barriers may intensify financial toxicity among Spanish-speaking patients by limiting their ability to understand and communicate financial concerns. This study examines how language barriers may worsen financial toxicity for Spanish-speaking patients undergoing cancer treatment. Methods: Nine Health medical providers were interviewed about their experiences caring for Spanish-speaking patients undergoing cancer treatment. Participants included oncologists, surgeons, pharmacists, nurses, social workers, patient navigators, and interpreters. Interviews explored communication of financial information, available resources, the impact of language barriers, and how financial stress affects patient health and treatment. Results: Four of nine interviewees reported interacting with Spanish-speaking patients daily, three interacted more than twice per week, and two interacted once per week or less. Despite these interactions, seven of nine providers were unaware of how patients receive information regardingtreatment-related financial costs. Discussion of financial concerns varied by provider: three addressed finances at every visit, three rarely discussed them, one did so in about half of visits, and two raised the issue only when patients struggled with copayments. Providers identified common financial challenges, including transportation, rent, food insecurity, housing instability, family expenses, loss of income, and copayments. These challenges were reported to limit or interrupt treatment, delay diagnoses, and increase stress for patients and their families. Although financial resources were described as limited for all patients, Spanish-speaking patients face additional barriers, including English-only materials, fear related to legal status, and limited access to Spanish-speaking staff. Proposed solutions included early financial screening, increased use of in-person interpreters, physician training on treatment costs, and multilingual educational materials. Conclusions: Financial toxicity negatively affects treatment continuity and patient well-being. Spanish-speaking patients are disproportionately impacted due to language-related barriers. Early financial screening and improved language support may help mitigate these challenges. Future research will involve interviewing Spanish-speaking patients to compare patient and provider perspectives and identify strategies to better support patients experiencing financial hardship.
Single-cell spatial analysis of the tumor immune microenvironment in NSCLC primary tumors and brain metastases.
8585 Background: Brain metastases (BrM) are associated with poor prognosis in non-small cell lung cancer (NSCLC). Although immune checkpoint inhibitors (ICIs) demonstrate intracranial activity, intracranial progression remains common, especially in patients with driver-negative NSCLC. To define mechanisms of intracranial immune resistance, we applied imaging mass cytometry to profile the tumor immune microenvironment (TIME) in BrM and primary lung tumors. Methods: Forty-four patients with advanced driver-negative NSCLC were included; 39 (89%) were treated with ICIs. A 40-marker antibody panel enabled site-specific immune phenotyping of primary lung tumors and BrM, with all samples obtained prior to initiation of systemic immunotherapy. Three regions of interest per sample (two intratumoral, one peritumoral) were analyzed using a Hyperion imaging mass cytometer. Single-cell segmentation was performed using Mesmer with immune phenotypes defined by marker expression. Spatial neighborhoods were identified using unsupervised k-means clustering of nearest-neighbor-derived local cellular compositions. Results: Compared with primary lung tumors, BrM demonstrated significantly reduced CD4⁺ and CD8⁺ T cells (p < 0.001), B cells (p = 0.017) and endothelial markers (p < 0.001). Despite reduced overall CD4⁺ infiltration, BrM exhibited higher proportions of regulatory T cells (Tregs; p = 0.017), Ki67⁺CD4⁺ T cells (p = 0.002) and Ki67⁺ Tregs (p = 0.017). BrM were enriched for CD206-high immunosuppressive macrophages, whereas primary tumors demonstrated predominance of CD11c-high inflammatory myeloid cells (p = 0.006). Spatial analysis demonstrated increased proximity of CD8⁺ T cells (p = 0.039) and Tregs (p = 0.020) to M2-like macrophages in BrM. Neighborhood analysis revealed site-specific immune organization, with primary tumors enriched for adaptive immune-dominant niches containing mixed CD4⁺, CD8⁺ and B-cell populations. In contrast, BrM were characterized by myeloid-T-cell interface neighborhoods marked by close spatial coupling of T cells with macrophages and monocytes. In primary tumors, durable immunotherapy benefit (≥24-month PFS and OS) was associated with significantly higher CD8⁺ and CD4⁺ T cells, B cells, dendritic cells, monocytes and macrophages. In BrM, no consistent immune correlates of long-term benefit were observed. Conclusions: NSCLC BrM exhibit a distinct TIME characterized by depleted adaptive immune infiltration, CD206-high macrophage dominance and myeloid-T-cell spatial organization. While primary lung tumors display adaptive immune signatures predictive of durable ICI benefit, BrM lack consistent immune correlates of response. These site-specific compositional and spatial differences provide a mechanistic framework for the attenuated and less durable intracranial responses to immune checkpoint blockade.
Operational and clinical drivers of subcutaneous PD-1/PD-L1 inhibitor adoption: A mixed-methods analysis of U.S. oncology practice patterns.
1550 Background: Subcutaneous (SC) formulations of PD-1/PD-L1 inhibitors have recently been approved across multiple solid tumors. While these agents offer operational and patient-centric advantages, their perceived clinical value relative to established intravenous (IV) formulations remains unclear. Understanding real-world oncologist perceptions may inform future adoption patterns and practice impact. Methods: A national mixed-methods study surveyed 102 U.S. hematologist-oncologists from academic (44%, n=45) and community (56%, n =57) practices across all U.S. regions (Nov- Dec 2025). A structured online questionnaire assessed brand utilization, regimen sequencing, physician satisfaction, switching behavior, and perceived comparative benefit between pembrolizumab- and nivolumab-based therapies using Likert-type scales and utilization metrics. All participants met predefined patient volume and clinical practice criteria. Eight qualitative interviews explored drivers of brand choice, sequencing, and switching decisions. Results: Across tumor types, oncologists reported modest current use of SC PD-1/PD-L1 inhibitors, with incremental uptake expected over the next six months. SC formulations were viewed as convenience-enhancing rather than clinically transformative, with reduced chair time (75% reporting significant benefit), improved infusion center efficiency (68%), and better patient experience (70%) cited as key benefits. Approximately half of PD-1/PD-L1–eligible patients across NSCLC, melanoma, and RCC were considered suitable for SC administration. Perceived benefit was largely limited to monotherapy and maintenance settings, with limited added value in curative-intent or combination regimens where infusion time is driven by other agents. In NSCLC, projected near-term uptake of SC PD-1/PD-L1 therapy was highest among PD-L1–high patients receiving monotherapy, while in melanoma and RCC, SC was more often positioned later in the treatment sequence, particularly after treatment stability. Insurance coverage (39% reporting a significant barrier) and cost (58%) were the primary barriers to broader adoption, outweighing concerns about safety (22%) or efficacy (27%). Overall uptake was expected to primarily substitute for IV monotherapy rather than expand total PD-1/PD-L1 use. Conclusions: U.S. oncologists view SC PD-1/PD-L1 inhibitors as operational alternatives to IV therapy, with adoption driven by efficiency and patient convenience and constrained by payer dynamics. SC administration is best positioned to enhance care delivery in monotherapy and maintenance settings, with limited incremental value in curative-intent or combination regimens. Addressing real-world access barriers will be key to broader integration across solid tumors.
Objective response rates with Ori-C101, an armored GPC3-directed CAR-T, in heavily pretreated advanced HCC: Updated results from the phase Ib BEACON study.
2508 Background: Advanced hepatocellular carcinoma (HCC) remains a high unmet-medical-need malignancy with limited therapeutic options. Ori-C101 is a novel, armored, autologous GPC3-directed CAR-T cell therapy. Following promising results from early-phase trials (ChiCTR190028121; NCT05652920, BEACON study), we shall herein update outcomes from the BEACON study with focusing on long-term safety, durability of response, and survival after more than 2 years of follow-up. Methods: This is an open-label, multi-center, phase Ib dose-escalation and expansion study enrolled patients (pts) with GPC3 + advanced HCC who had progressed on ≥2 prior lines of systemic therapy (including ICIs and TKIs). A single dose of Ori-C101 was administered via hepatic arterial infusion to enhance regional cell delivery. Integrated analyses assessed safety, tolerability, PK, and efficacy (per RECIST v1.1)，aiming to determine the RP2D. Results: As of Dec 24, 2025, 19 pts received Ori-C101 infusion across 4 dose levels (DLs). All pts had BCLC stage B/C disease and 31.6% (6/19) had extrahepatic metastases. Pts were previously treated with a median of 3 lines (range 2–8) therapies. Safety: Safety remained manageable; no late-onset nor cumulative toxicities were observed through the extended follow-up period. The most common ≥G3 TEAEs (≥10.0%) were transient hematologic toxicities and hepatic laboratory abnormalities. CRS occurred in 100.0% (19/19) of pts; while ≥G3 CRS observed in 42.1% (8/19). No ICANS occurred. One pt at DL4 experienced a DLT of G4 CRS complicated by secondary DIC. Efficacy: In 18 efficacy-evaluable pts, Ori-C101 demonstrated a robust dose-dependent response. Confirmed ORR was 50.0% (9/18); DCR was 77.8% (14/18). At RP2D (DL3), the confirmed ORR and DCR were 66.7% (6/9) and 88.9% (8/9), respectively. Critically, responses were not only rapid but also remarkably durable. 88.9% (8/9) of responders achieved objective response within 1.1 months; at M3, 83.3% (5/6) of responders at the RP2D remained PR. Notably, 1 pt at DL4 achieved CR with a duration exceeding 20 months. Preliminary overall survival data indicate a substantial long-term survival benefit with a median OS of 14.4 months (range 2.6–22.0). In addition, Dose-Exposure-Responses analysis showed dose-dependent CAR-T cells expansion, pharmacodynamic effects and improved tumor response. Conclusions: Ori-C101 demonstrates a manageable safety profile and compelling, durable anti-tumor activity in GPC3 + advanced HCC. The combination of high ORR and prolonged survival benefit distinguishes Ori-C101 as a potential paradigm-shifting therapy for patients who have failed standard-of-care treatments. A phase II/III study is currently underway to further confirm the efficacy and asses the safety of Ori-C101. Clinical trial information: NCT05652920 .