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Response to cancer immunotherapy for p53 antibody-positive non-small cell lung cancer according to treatment regimen.
8589 Background: Cancer immunotherapy has enabled long-term survival in advanced non-small cell lung cancer (NSCLC), but there are some patients with resistance to cancer immunotherapy. Mutations in the p53 gene have been reported to suppress immunity in the tumor immune microenvironment and influence resistance to cancer immunotherapy. Serum p53 antibody is an autoantibody produced in association with p53 gene mutations. However, it is unclear whether p53 antibody-positive NSCLC correlates with treatment response to cancer immunotherapy, particularly whether treatment response differs according to the treatment regimen. Methods: Participants were patients with advanced NSCLC who received immune checkpoint inhibitors (ICI) with or without chemotherapy at our hospital from November 2018 to June 2024. Blood samples were obtained before and after treatment with ICI and serum p53 antibody levels were measured. We compared the serum anti-p53 antibody and treatment response (early progressive disease, progression-free survival, and overall survival). Furthermore, we investigated whether treatment response of cancer immunotherapy in p53 antibody-positive NSCLC differs according to the treatment regimen. Results: A total of 173 patients were enrolled (mean age 69.4 years, 76.7% male, 58.4% adenocarcinoma). The regimen of ICI with chemotherapy was more common in 130 cases (75.1%) than ICI alone. There were 70 patients (40.4%) who were positive for serum p53 antibody before treatment. The p53-positive group had a significantly higher early progressive disease than the p53-negative group in the patients who received ICI with chemotherapy (28.6% vs 15.5%, p = 0.04). Multivariate analysis showed that serum p53 antibody was the only factor significantly associated with early progressive disease (HR 3.11, 95%CI 1.19-8.50, p = 0.02). PFS was significantly shorter in the p53-positive group than in the p53-negative group in patients with PD-L1 low expression (0-49%) (3.7m vs 7.2m, p = 0.01). Regarding the impact of treatment regimens on treatment response, there was no difference based on ICIs with or without chemotherapy. However, the group that combined anti-VEGF antibodies with ICIs had a significantly lower early progressive disease rate than the group that did not combine them (14.3% vs 30.2%, p = 0.03). Conclusions: Serum p53 antibody influenced the therapeutic efficacy of cancer immunotherapy in NSCLC. p53 antibody-positive NSCLC demonstrated differing treatment responses depending on therapeutic regimen. We believe that the combination of ICIs and anti-VEGF antibodies is a promising treatment option for p53 mutation-positive NSCLC.
First-in-human study to evaluate the safety, tolerability, and PK of EIK1005, a novel WRN inhibitor in healthy participants.
e15110 Background: Cancers with deficient mismatch repair (dMMR) have high microsatellite instability (MSI-H) and are reported to be sensitive to Werner syndrome helicase inhibition (WRNi), via synthetic lethality. WRNi in MSI-H cells leads to loss of genomic integrity and ultimately cell death while not affecting microsatellite stable (MSS) and healthy cells. SOC for patients with MSI-H tumors includes surgery and immunotherapy (checkpoint inhibitors [CPIs] such as pembrolizumab [pembro]), however ~30 to 50% of patients do not respond to first-line immune CPIs or acquire resistance. A critical unmet medical need exists for new therapies. EIK1005, a novel, potent and selective WRN inhibitor has potential for targeted antitumor activity in MSI-H or dMMR solid tumors. EIK1005 demonstrated in vitro activity leading to cell death in MSI-H cells while sparing microsatellite stable (MSS) cancer and healthy cells. In in vivo mouse studies, EIK1005 was well-tolerated and had robust antitumor effects. Based on the mechanism of action and favorable nonclinical pharmaceutical and toxicology profile, EIK1005-001 was planned. Methods: EIK1005-001 is a Phase 1 randomized, double-blind, single ascending dose study evaluating the safety, tolerability and pharmacokinetic (PK) profile of EIK1005 in healthy participants (pts). In Period 1 (P1) and Period 2 (P2), a single dose of EIK1005 or placebo, was given to pts in a fasted and fed state, respectively. Safety follow-up ensued (clinical research unit stay of 3 days; follow-up through Day 36). 8 pts were randomized 3:1 at each dose level (DL) in P1, then a DL was chosen for P2 (EIK1005 50 mg). Results: At data cutoff (13 Oct, 2025), 23 pts (P1 [n = 15; 11 active, 4 placebo] and P2 [n = 8; 6 active, 2 placebo]) were randomized to receive EIK1005 (P1: 50 mg [n = 5], 100 mg [n = 6]), or placebo (n = 4); in P2, 50 mg (n = 6) or placebo (n = 2). All pts completed the study. In the safety population (17 active, 6 placebo), EIK1005 was well tolerated; all AEs were unrelated and mild, except one moderate AE, with no clinically significant events. Median Tmax (P1) was 3-4 hours, and T 1/2 was 9.4 days (post 100 mg). Descriptive PK results indicated that EIK1005 exposure increased in a dose-related manner; no clinically significant food effect was observed in the parallel group assessment of EIK1005 50 mg (P1, P2); dosing can occur without regard to food. Urine PK parameters were noncalculable indicating that renal excretion was negligible. Multiomics analysis did not reveal any changes in protein expression (up to 72 hours), or in RNA gene expression profiles (up to 24 hours) in blood after single doses, consistent with WRNi having no measurable activity in MSS cancer or healthy cells. Conclusions: EIK1005 had a favorable safety profile at the 50 and 100 mg single doses evaluated in healthy pts. PK and safety data support a starting dose of 50 mg given in patients in EIK1005-002 (NCT#007262619). Clinical trial information: ACTRN12625000334404.
Application of a neoadjuvant 21-gene breast recurrence score assay to redirect surgical and systemic treatment pathways in early breast cancer: A multicenter prospective study.
596 Background: The 21-gene Oncotype DX Breast Recurrence Score assay is well established for determining use of adjuvant chemotherapy in hormone receptor (HR)-positive, HER2-negative breast cancer patients. However, the role of the 21-gene assay in the neoadjuvant setting has yet to be established. We previously reported the impact of the 21-gene assay in the neoadjuvant setting in node-negative breast cancer patients, which led to a reduction in the recommendation of chemotherapy in about one-third of patients. Here, we report the impact of the assay on neoadjuvant treatment pathways including surgery, endocrine therapy, and chemotherapy, in addition to overall costs. Methods: We performed a multicentre, prospective observational trial of HR-positive, HER2-negative breast cancer patients with T2-T3 disease and clinically negative axillary lymph nodes. Physicians completed questionnaires prior to and after Recurrence Score (RS) results, indicating their treatment choice for neoadjuvant endocrine or chemotherapy, or upfront surgery. Data was also collected at 6 months after initiation of therapy, to verify treatment received. The primary and secondary objectives were to evaluate impact of RS results on physician’s treatment decisions and on drug (anti-emetics and pre-medication), and nursing (counselling and infusion time) costs, respectively. Results: A total of 70 patients were enrolled in the study as part of five hospital centers of the McPeak Sirois Group in the province of Quebec from 2018-2021. Feasibility of the 21-gene assay from core biopsy samples was 98.6%. At 6-month follow-up, the 21-gene assay led to a change in treatment decision in 52.2% of patients, including de-escalation from neoadjuvant chemotherapy to either upfront surgery in 21.7%, or to neoadjuvant endocrine therapy in a further 21.7%. The use of upfront surgery changed from 10.0% at baseline to 33.3% at 6-month follow-up ( p = 0.0004). Use of neoadjuvant endocrine therapy also changed from 12.9% to 29.0% ( p = 0.02). Among patients treated with upfront surgery or neoadjuvant endocrine therapy, 52.2% and 55.0% of patients, respectively, had a RS≥16. At baseline, for all patients, total chemotherapy-associated drug costs were $190,656 CAD, and nursing-associated costs were $96,918 CAD. RS-guided treatment recommendation reduced chemotherapy-associated drug costs by 32.3% and nursing resource utilization by 44.1%. Conclusions: The use of the 21-gene assay reclassified treatment pathways in 52.2% of patients, including shifting patients from neoadjuvant chemotherapy toward upfront surgery or neoadjuvant endocrine therapy, while reducing chemotherapy-related resource utilisation. These data support the use of the 21-gene assay as a clinical decision-making tool in the neoadjuvant setting. Additional information: Coauthor André Robidoux, MD, died in July 2020.
Body mass index and the risk of hematologic adverse events in HR+/HER2- breast cancer patients treated with CDK4/6 inhibitors.
e24150 Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors has been established as the recommended therapy for hormone receptor-positive and human epidermal growth factor 2-negative (HR+/HER2-) breast cancer (BC). However, the evidence on the relation between BMI and CDK4/6 inhibitor-related hematologic adverse advents (AEs) remain limited. Therefore, this study aimed to investigate the association between BMI and the risk of CDK4/6 inhibitor-related AEs in patients with HR+/HER2- BC. Methods: This single-center, retrospective cohort study at Sun Yat-Sen Memorial Hospital between January 8, 2019 and April 1, 2025 included patients with HR+/HER2- BC receiving CDK4/6 inhibitor and had a baseline BMI. Those who were treated with CDK4/6 inhibitors in the neoadjuvant setting or had incomplete clinical data were excluded. BMI was dichotomized based on the Working Group on Obesity in China (WGOC) criteria: <24 kg/m 2 vs. ≥24 kg/m 2 . The primary endpoint was incidence of grade≥3 neutropenia. The secondary endpoints were grade≥3 of overall and other hematological AEs separately, including leukopenia, anemia, thrombocytopenia, and lymphopenia, as defined in version 5.0 of the Common Terminology Criteria for Adverse Events (CTCAE). Group differences were assessed using Chi-square or Fisher’s exact tests. The Wald method was used to calculate the rate difference (RD) and 95% confidence interval (CI). Results: Among 740 included HR+/HER2- BC patients, 424 (57.3%) were BMI <24 kg/m 2 and 316 (42.7%) were BMI ≥24 kg/m 2 . Patients with BMI ≥24 kg/m 2 tended to be older and with higher Eastern Cooperative Oncology Group (ECOG) score. There were no significantly statistical differences in the type of CDK4/6 inhibitors used, with more than half of patients using abemaciclib in both groups. Patients with BMI ≥24 kg/m 2 had a significantly lower incidence of grade ≥3 neutropenia (RD = -10.5%, 95% CI = -17.0% to -4.1%, P = .002), along with lower rates of leukopenia (RD = -8.9 %, 95% CI = -14.6% to -3.1%, P = .004). Conclusions: Higher BMI is associated with less severity of CDK4/6 inhibitor-induced hematologic AEs, notably neutropenia and leukopenia. Further studies are needed to elucidate the mechanisms and optimize treatment to minimize these AEs. Association between BMI and grade≥3 hematologic AEs on CDK4/6 inhibitors. Adverse Event BMI<24 kg/m², No. (%) BMI≥24 kg/m², No. (%) Rate Difference, 95% CI (%) P Neutropenia 144 (34.0) 74 (23.4) -10.5 (-17.0 to -4.1) .002 Leukopenia 106 (25.0) 51 (16.1) -8.9 (-14.6 to -3.1) .004 Anemia 21 (5.0) 11 (3.5) -1.5 (-4.4 to 1.4) .33 Thrombocytopenia 15 (3.5) 6 (1.9) -1.6 (-4.0 to 0.7) .18 Lymphopenia 100 (23.6) 70 (22.2) -1.4 (-7.5 to 4.7) .65 Any adverse event 218 (51.4) 140 (44.3) -7.1 (-14.4 to 0.1) .06 BMI=body mass index, AEs=adverse events, CDK=cyclin-dependent kinase.
Pathologic complete response after neoadjuvant chemotherapy in triple-negative invasive lobular carcinoma: A meta analysis.
e12681 Background: Triple-negative invasive lobular carcinoma (TN-ILC) is a rare TNBC subtype with limited evidence to guide systemic therapy. Neoadjuvant chemo-immunotherapy is standard for stage II–III TNBC, yet expected pathologic complete response (pCR) rates in TN-ILC remain unclear. Given the distinct biology and lower chemosensitivity of ILC, we performed a systematic review and meta-analysis to define pCR rates in TN-ILC. Methods: We conducted a systematic review of studies reporting pCR in patients with TN-ILC treated with neoadjuvant systemic chemotherapy. PubMed, Cochrane Library, and Web of Science were searched, with manual review of ASCO and ESMO abstracts, through January 23, 2026. Pooled pCR estimates were calculated using logit-transformed random-effects models, excluding single-case reports and studies with < 2 TN-ILC patients. Heterogeneity was assessed using I², and survival outcomes were summarized descriptively due to inconsistent reporting. Results: Of 68 studies identified, 5 met inclusion criteria; two large registry-based neoadjuvant cohorts comprising 425 TN-ILC patients contributed to the pooled analysis. Study-level pCR rates ranged from 20.5% to 23.2%. The pooled pCR rate following neoadjuvant chemotherapy was 22.5% (95% CI: 18.8-26.7%) with no observed heterogeneity (I² = 0%). Details regarding survival outcomes, CT regimens, including anthracycline use, platinum exposure, and incorporation of IO, were variably reported and could not be analyzed quantitatively. Conclusions: Approximately one in five patients with TN-ILC achieve pCR following neoadjuvant CT, supporting the use of neoadjuvant systemic therapy despite limited representation of this rare histologic subtype in prospective trials. However, these pCR rates are lower than those reported in contemporary unselected TNBC cohorts treated in prospective studies. Importantly, most available TN-ILC–specific evidence predates the routine incorporation of IO, which is now standard in early-stage TNBC; therefore, the magnitude of benefit from CT-IO in TN-ILC remains unknown and represents a key limitation of this analysis. Future registry-based analyses including survival outcomes, molecular characterization, and standardized TN-ILC–specific reporting within modern CT-IO trials are needed to better define optimal treatment strategies for this rare subtype. pCR Outcomes in TN-ILC with neoadjuvant chemotherapy. Group / Study TN-ILC (n) pCR (n/N) pCR %, 95% CI Pooled estimate (primary) 425 95/425 22.5 (18.8-26.7) Joshi et al., 2023 298 69/298 23.2 (18.7-28.3) Riba et al., 2019 127 26/127 20.5 (14.4-28.3) Case reports† 4 2/4 50.0 (15.0-85.0) †Case reports are summarized descriptively and were not included for statistical inference.
Longitudinal circulating tumor DNA surveillance as predictor of progression in advanced non-small-cell lung cancer with long-term benefit to immunotherapy.
8540 Background: Radiographic assessments often lag behind biological progression, and reliable biomarkers to stratify the post-treatment progression risk remain lacking in advanced non-small-cell lung cancer (NSCLC). The clinical utility of minimal residual disease in advanced solid tumors also requires further evaluation. We investigated ctDNA-based post-immunotherapy molecular residual disease (ctDNA-iMRD) in advanced NSCLC with long-term benefit from immunotherapy and assessed its predictive value for subsequent progression. Methods: This prospective, observational, multicenter CR1STAL study, is designed to evaluate whether longitudinal ctDNA-iMRD surveillance can can stratify progression risk in advanced NSCLC patients with long-term benefit from immunotherapy (defined as non-PD at 12 months after treatment initiation). The primary endpoint was progression-free survival (PFS), defined as the time from enrollment to radiographic progression or death. For ctDNA detection, tumor-informed and tumor-agnostic approaches were selected according to tumor tissue availability. ctDNA-iMRD positive was defined as detectable ctDNA at at any surveillance timepoint. Results: A total of 97 advanced NSCLC patients were included, comprising 46 in the tumor-informed cohort and 51 in the tumor-agnostic cohort. At median follow-up of 36.4 months and a median ctDNA-iMRD surveillance duration of 10.5 months, 49 patients (50.5%) were classified as ctDNA-iMRD positive during longitudinal monitoring. Patients who were ctDNA-iMRD positive had a significantly shorter median PFS than those who remained ctDNA-iMRD negative (10.1 months vs not reached; HR = 4.85; 95% CI, 2.66 to 8.82; p < 0.001). ctDNA-iMRD detectable preceded radiographic progression by a median of 5.9 months. The positive and negative predictive values of longitudinal ctDNA-iMRD surveillance were 85.1% and 72.7%, respectively. Between ctDNA detection approachs, ctDNA-iMRD positive was strongly associated with increased progression risk in both the tumor-informed (HR = 6.29; p < 0.001) and tumor-agnostic (HR = 3.67; p < 0.001) cohorts. In addition, longitudinal ctDNA-iMRD negative was associated with long-term overall survival (HR = 0.22, 95% CI, 0.09 to 0.55; p < 0.001), with 2-year and 3-year OS rates of 97.2% and 89.8%, respectively. Furthermore, ctDNA clonal status and high ctDNA growth rates were correlated with early progression. Conclusions: Both tumor-informed and tumor-agnostic ctDNA-iMRD approaches showed strong predictive performance. Longitudinal ctDNA-iMRD surveillance effectively stratified advanced NSCLC patients at high risk of progression after achieving long-term benefit from immunotherapy, supporting its potential role in enabling earlier, risk-adapted intervention in future prospective studies. ClinicalTrials.gov Identifier: NCT05198154.
Meaning, distress, and desire for hastened death in homebound adults with advanced cancer: A cluster analysis.
12071 Background: Patients with advanced cancer experience significant anxiety and depression exacerbating existential distress, which is often defined as a loss of meaning and dignity, desire for death, hopelessness, and/or demoralization. Such distress is even more pronounced for homebound adults with cancer who are isolated and engage less in enjoyable activities. While meaning in life, affective distress, and existential distress are related, discrepancies exist in the literature which may reflect the presence of distinct psychosocial profiles as opposed to inconsistencies in the literature. Methods: Patients with advanced cancer ( N = 64) who had recently completed an episode of home care and completed baseline assessments in a pilot randomized controlled trial (RCT) of Meaning-Centered Psychotherapy for Hospitals, Hospice, and Home (MCP-H) served as the study sample. Baseline assessments included measures of meaning in life, anxiety, depression, and desire for hastened death. A hierarchical agglomerative cluster analysis was conducted to identify naturally occurring subgroups of participants. Subgroup differences in predictor variables, physical symptom burden, and demographic variables were explored. Results: A 2-cluster solution emerged from the data: Low Meaning, High Distress and DHD ( n = 29; 45.3%) and High Meaning, Low Distress and DHD ( n = 35; 54.7%). Subgroups were statistically discrepant on measures of meaning in life ( d = 0.57), anxiety ( d = 3.07), depression ( d = 2.57), and DHD ( d = 2.76), with medium to large effect sizes. Subgroups were also significantly different in physical quality of life ( d = 16.50). No significant differences were noted demographically between subgroups. Conclusions: To our knowledge, this is the first cluster analysis investigating affective and existential distress in a population of homebound adults with advanced cancer. Results suggest the possibility of 2 distinct subgroups of homebound cancer patients, the first of which is prone to clinically significant anxiety, depression, and moderate DHD, possibly due to a subtle difference in meaning in life. Results also point to physical symptom burden and quality of life being exponentially impacted by affective and existential distress. This study provides valuable information which can aid assessment and treatment for vulnerable homebound adults with advanced cancer.
Durable treatment-free remission in CML beyond clinical trials: Lessons from a large single-center real-world experience.
6582 Background: Treatment-free remission (TFR) has become a major therapeutic objective in chronic-phase chronic myeloid leukemia (CML). While clinical trials have established the feasibility of TFR, real-world data evaluating the influence of deep molecular response (DMR) duration, cumulative tyrosine kinase inhibitor (TKI) exposure, and adherence to molecular monitoring remain limited, particularly in resource-constrained settings. Methods: We conducted a retrospective single-centre analysis of chronic-phase CML patients who electively discontinued TKI therapy between May 2019 and October 2025 after achieving sustained DMR (BCR-ABL ≤0.01% IS). Collected variables included demographics, ELTS risk score, TKI type, duration of DMR (<5 vs ≥5 years), cumulative TKI exposure (<8 vs ≥8 years), molecular relapse (loss of major molecular response [MMR]), time to relapse, and time to MMR regain following TKI resumption. Monitoring compliance was defined as completion of at least five PCR assessments in the first year following TKI discontinuation. Relapse-free survival was analyzed using Kaplan–Meier methods. Results: Eighty-eight patients were included (median age 36 years; 53.4% male). Median cumulative TKI exposure prior to discontinuation was 14.5 years, and median DMR duration was 13 years. At a median follow-up of 40 months, 72 patients (81.8%) remained in sustained TFR. TFR rates were 92% at 6 months, 87% at 12 months, and 82% at 24 months. Fourteen patients (15.9%) restarted TKI therapy due to molecular relapse, one due to withdrawal symptoms, and two died from causes unrelated to CML. Median time to relapse was 4.5 months, with the majority occurring within the first six months.No patient progressed to accelerated or blast phase. All evaluable patients who resumed TKI therapy rapidly regained MMR (median 3 months). TFR rates did not differ significantly according to DMR duration (<5 vs ≥5 years; p =0.67), cumulative TKI exposure (<8 vs ≥8 years; p =0.70), or compliance with molecular monitoring (compliant vs non-compliant; p =0.82). Notably, 30.6% of patients were non-compliant with recommended monitoring schedules, yet high TFR rates and excellent salvage outcomes were maintained. Conclusions: In this large single-centre real-world cohort, over 80% of chronic-phase CML patients achieved durable TFR with predictable early relapses, excellent salvage outcomes, and no disease progression. Neither prolonged DMR duration, extended TKI exposure, nor strict adherence to intensive molecular monitoring significantly influenced relapse risk. These findings support broader, pragmatic implementation of TFR strategies and suggest that less stringent molecular monitoring may be safely adopted in carefully selected patients, particularly in resource-limited settings.
Multi-omic profiling to clarify mechanisms of therapy-induced prostate cancer lineage plasticity.
e17077 Background: Prostate adenocarcinomas are the most common form of the disease. Targeting the androgen receptor (AR) is the principal treatment strategy. However, resistance is common. Lineage plasticity (LP)—or change in cell state—is increasingly recognized as a mechanism of resistance to AR-targeting therapies. LP is a continuum, including amphicrine, double negative prostate cancer (DNPC), and neuroendocrine prostate cancer (NEPC). Despite the increasing incidence of LP due to more widespread use of potent AR inhibitors, mechanisms by which LP emerges after therapy have been understudied due to the paucity of matched patient tumor biopsies. To address this deficit, we performed multi-omic and spatial profiling on matched treatment-naïve prostate biopsies and post-treatment metastatic biopsies. Methods: We examined matched biopsies from 16 patients including seven whose progression tumors had evidence of LP. We performed DNA-sequencing to identify mutations and copy number alterations. We performed RNA-sequencing to transcriptionally subtype all tumors. We also performed spatial transcriptomic profiling with 10X Visium in a subset of matched samples with evidence of LP to infer copy number alterations and to understand the interactions between specific tumor populations and the tumor microenvironment (TME). Results: RNA-sequencing identified pathways linked to proliferation and inflammatory signaling to be highly activated in baseline tumors that eventually underwent LP and clarified distinct LP trajectories. DNA-sequencing revealed specific genomic patterns in TP53 and RB1 at baseline and progression linked to distinct LP trajectories vs. maintenance of an AR-driven phenotype. We confirmed that the genomic patterns seen in the distinct LP trajectory samples from our cohort were also present in similar therapy-induced LP samples from independent cohorts. Unbiased clustering of spatial transcriptomics data revealed seven tumor clusters. Inferred copy number analysis implicated either clonal selection or divergent clonal evolution in specific tumors that underwent LP. Conclusions: Multi-omic analysis clarifies baseline molecular features linked to specific LP trajectories and mechanisms that may contribute to the emergence of those trajectories. These results provide clues about why certain patient tumors may be at risk of undergoing specific LP trajectories with treatment. TME analysis to understand the influence of specific immune populations on cell state heterogeneity is ongoing.
Adaptive phase 2/3 study of EIK1001, a TLR7/8 dual agonist, in combination with pembrolizumab, as first-line therapy in participants with advanced melanoma (TeLuRide-006).
TPS9601 Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1 antibodies, reverse tumor induced immune suppression and promote effective anti-tumor T-cell responses. They have drastically improved outcome in advanced melanoma therapy, yielding durable improvements in progression-free survival (PFS) and overall survival (OS). Although adding anti-CTLA-4 or anti-LAG-3 enhances efficacy beyond anti-PD-1 alone, these approaches do not directly target dominant myeloid-mediated resistance mechanisms within the tumor microenvironment, and new agents targeting this axis are needed. EIK1001, a TLR7/8 dual-agonist, activates myeloid and plasmacytoid dendritic cells to stimulate innate inflammation and adaptive immunity. Across multiple studies, EIK1001 has been well tolerated and has demonstrated clinical activity both as monotherapy and in combination with ICIs. Methods: TeLuRide-006 (NCT#06697301) is a global, multicenter, randomized, double-blind, adaptive Phase 2/3 trial of EIK1001 or placebo, in combination with pembrolizumab (pembro), as first-line therapy for participants (pts) with advanced cutaneous melanoma. Approximately 740 pts will be randomized, including a dose-optimization (DO) stage in which pts are randomized 1:1:1 to two EIK1001 dose levels or placebo, each administered with pembro, followed by Phase 2/3 expansion evaluating the selected EIK1001 dose versus placebo, with pembro. Interim analyses will guide progression from DO to Phase 2 and subsequently to Phase 3. EIK1001 or placebo is administered IV QW until the end of Week 27 then Q3W; while pembro is administered IV Q3W. Pts are stratified by prior anti-PD-1 adjuvant therapy, LDH level, and BRAF mutational status. Key eligibility criteria include patients ≥12 years (with country-specific variations), life expectancy ≥3 months, unresectable Stage III or Stage IV melanoma, known BRAF V600 status, at least one RECIST v1.1–measurable lesion, and no prior or current pneumonitis/interstitial lung disease. Primary objectives are to assess the efficacy and safety of two EIK1001 doses with pembro in DO, and to compare PFS (RECIST v1.1 by blinded independent central review [BICR]) and OS between the selected EIK1001 dose and placebo in combination with pembro. Secondary objectives include safety and tolerability of either EIK1001 dose with pembro, objective response rate and duration of response per RECIST v1.1 by BICR. Exploratory objectives include time to response, EIK1001 exposure-response relationships, and health-related quality of life. This study enrolled (randomized) its first participant on 5/21/2025 and is activated at 91 sites in 22 countries at the time of abstract submission.
Nivolumab and ipilimumab as second or later line therapy in hepatocellular carcinoma: A retrospective study.
e16167 Background: Despite advances in first-line for systemic therapy in hepatocellular carcinoma (HCC), tumor progression remains common. However, the efficacy and safety of nivolumab plus ipilimumab (NIVO+IPI) as second or later line treatment in HCC remains limited. Methods: We retrospectively reviewed consecutive HCC patients who received NIVO (1mg/kg) and IPI (3mg/kg) every 3 weeks as later-line between Oct 2020 and Jun 2025. Endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs). Results: A total of 49 patients (Barcelona Clinic Liver Cancer stage B/C: 15/34) were included. Median age was 53 years (range 24–68). And 24, 14, and 11 patients received NIVO+IPI regimen as 2-, 3-, and 4-line therapy, respectively. Prior systemic regimens included PD-1/PD-L1 inhibitor plus anti-VEGF (38.8%), PD-1 inhibitor plus tyrosine kinase inhibitor (TKI, 42.9%), TKI alone (10.2%), PD-1 inhibitor alone (6.1%) or dual immunotherapy (2.0%). All patients had received prior local treatments. Median number of treatment cycles was 2 (range: 1-20). Among 32 evaluable patients, ORR was 12.5% (4/32) for the whole cohort, including 6.3% (2/32) complete response (CR), with 11.8% (2/17), 20% (2/10) and 0% (0/5) for 2-L, 3-L, and 4-L patients, respectively. And DCR was 56.3% (18/32) for the whole cohort, with 58.8% (10/17), 50% (5/10) and 60% (3/5) for 2-L, 3-L, and 4-L patients, respectively. With a median follow-up of 12 months, median PFS was 2.1 months (95% CI 2.0–4.2); the median duration of response was 3.4 months. The median OS was not reached, and 6, 12-month OS rates were 96.4% (95% CI 89.8%-100%) and 84.4% (95% CI 64.3%-100%). TRAEs of any grade occurred in 36.8% (18/49) and grade 3–4 TRAEs in 20.4% (10/49). The most common immune-related events were hepatitis (8.2%) and dermatitis (6.1%). Treatment discontinuation due to toxicity occurred in 4.1% (2/49), and no treatment-related deaths were observed. Conclusions: In this real-world cohort of HCC progressing on systemic and local therapies, NIVO+IPI demonstrated clinically meaningful efficacy and manageable toxicity as later line therapy. These data support NIVO+IPI as a viable salvage treatment option in the later line setting and warrant prospective evaluation.
Economic burden of non-approved alternative therapies among patients with stage IV cancer: A prospective observational study.
TPS11201 Background: Complementary and alternative therapies, including herbal supplements and over-the-counter medications, are used by 9 to 81% of cancer patients post-diagnosis to alleviate symptoms, side effects, anxiety, depression, or to gain a sense of control. Prior studies suggest higher use among younger, female patients with higher socioeconomic status. However, in our institutional practice, we did not observe any specific pattern on alternative medicine use. Additionally, the financial burden (financial toxicity) of these often-out-of-pocket expenses remains understudied in advanced cancer populations. This prospective observational study aims to assess the financial toxicity and describe patterns of use of non-approved alternative therapies among patients with stage IV cancer. Methods: This is a prospective, single-center, observational study conducted at Mercy Clinic Oncology, Fort Smith, AR. Eligible patients are aged ≥18 years, diagnosed with any stage IV cancer, and currently receiving systemic therapy. Key exclusions include the inability to read/understand English, incarcerated patients, and patients only on supportive care. A convenience sample of 150 patients will be enrolled for initial analysis with plans to expand the study to a multi-institutional format. Patients meeting eligibility criteria are identified via clinic schedule review and approached in person by a research nurse. Interested patients receive a study information sheet and complete a one-time, anonymous, paper-based survey (approximately 5 minutes) either in-clinic or at home (returned at next visit). The survey includes 6 demographic/cancer/treatment questions and 6 questions on use of specific non-approved alternative therapies and estimated average monthly costs (categorized as < $25, $26–$50, $51–$100, > $100). A specific question on marijuana addresses use for cancer cure (recreational/symptom control categorized as "no"); responses are anonymous with no PHI collected to minimize risk. Analysis will use descriptive statistics (frequencies/percentages) for cost patterns (primary outcome) and therapy types (secondary outcome), with chi-squared tests for subgroup comparisons by demographics. Enrollment started beginning of January 2026, and in two weeks, nine patients were identified and approached, with seven patients completing the survey. No preliminary data are available. Clinical trial information: Not applicable (IRB-approved observational protocol 24-062).
Knowledge distillation–enabled ResNet framework for hepatocellular carcinoma diagnosis on multiphase CT: Toward scalable global deployment.
4156 Background: Hepatocellular carcinoma (HCC) accounts for 85–90% of primary liver cancers and remains a leading cause of cancer-related mortality worldwide. Early and accurate imaging-based diagnosis is critical for staging, treatment selection, and survival. Multiphase contrast-enhanced CT is widely used for HCC detection, yet diagnostic accuracy varies due to lesion heterogeneity and radiologist workload. Deep learning models demonstrate high performance but are computationally intensive, limiting deployment in resource-constrained settings. Knowledge distillation enables transfer of diagnostic capability from large teacher models to lightweight student networks while preserving accuracy. We evaluated a ResNet-based distillation framework for efficient HCC diagnosis using multiphase CT imaging. Methods: We analyzed a curated dataset of 140 pathologically confirmed HCC cases, comprising arterial, portal venous, and delayed-phase CT images annotated by two expert radiologists independently . A high-capacity ResNet152 teacher model was trained to detect and localize HCC lesions using hierarchical residual feature learning across multiphase inputs. A compact ResNet18 student model was trained via temperature-scaled knowledge distillation using soft probability targets and regularized cross-entropy loss. Performance was evaluated using accuracy, sensitivity, specificity, F1 score, and AUROC. Computational efficiency and inference latency were assessed to determine real-world deployment feasibility. Results: The ResNet152 teacher achieved robust diagnostic performance ( > 97% accuracy) for HCC detection across lesion sizes and locations. The distilled ResNet18 preserved near-teacher accuracy, achieving AUROC exceeding 0.93 with balanced sensitivity and specificity ( > 93%). Knowledge distillation reduced model parameters by over 80% and substantially lowered inference time, enabling real-time execution on standard clinical hardware. Performance remained consistent across lesion diameter and hepatic segment subgroups, comparable to expert radiologist assessment Conclusions: Knowledge distillation enables a lightweight ResNet18 model to retain near–ResNet152 diagnostic performance for HCC detection on multiphase CT while markedly reducing computational requirements. This scalable framework addresses key barriers to AI adoption in oncology imaging and supports global deployment of AI-assisted HCC diagnosis. Prospective multicenter validation is warranted to assess clinical impact on early detection and treatment planning.
Comparative response assessment using PET-RANO 1.0 and RANO 2.0 in vorasidenib-treated <i>IDH</i> -mutant gliomas: The VORAFET study.
2073 Background: MRI-based response assessment may be suboptimal for capturing early treatment effects during isocitrate dehydrogenase ( IDH ) inhibition. We compared metabolic and morphological response classification using PET-RANO 1.0 and RANO 2.0 in vorasidenib-treated IDH -mutant gliomas and assessed treatment-related metabolic changes. Methods: All consecutive patients treated at Veneto Institute of Oncology and Padua University Hospital with vorasidenib (VOR) under a compassionate-use program (June 2024-March 2025) with baseline and follow-up [ 18 F]FET PET/MR were retrospectively included. Response was assessed every 3 treatment cycles according to PET-RANO 1.0 and RANO 2.0. PET-positive tumor volumes and tumor-to-background ratios (TBR max , TBR mean ) were analyzed. MRI response was evaluated using volumetric RANO 2.0 criteria. The VORAFET study was approved by the local Ethics Committee. Results: Twenty-six patients were included (10 astrocytomas, 16 oligodendrogliomas; 22 WHO grade 2, 4 non-enhancing WHO grade 3). Median follow-up from VOR initiation was 9 months (IQR 9-11). According to PET-RANO 1.0, partial metabolic responses (PET-PR) increased over time, from 20% at 3 months to 30.8% at 6 months and 63.6% at 9 months, while metabolic progression (PET-PD) was already detected in 18.2% at 9 months. In contrast, RANO 2.0 identified no partial responses at any timepoint, classifying most patients as stable disease (84.2%) or minor response (10.5%), with progression detected in only 5.3% at 9 months. Quantitative PET analysis showed an early and sustained reduction in metabolic activity. TBR mean decreased significantly at 3 months (mean difference [MD] -0.04; 95% CI -0.08 to -0.01) and continued to decline at 9 months (MD -0.07; 95% CI -0.11 to -0.02). Compared to baseline, at 9 months, TBR max decreased from 2.7 to 2.0 (MD -0.5; 95% CI -0.8 to -0.2) in all patients included. No significant changes were observed in PET volumes. Similarly, FLAIR-based tumor volume showed no significant variation (at 9 months: MD -2.2; 95% CI -5.1 to 0.7). Conclusions: PET-RANO 1.0 enabled earlier detection of treatment response and progression compared with MRI-based RANO 2.0, highlighting clinically relevant limitations of morphology-driven MRI-based assessment. These findings support the clinical integration of amino acid PET into response monitoring strategies and warrant prospective validation of PET-derived biomarkers in IDH- mutant gliomas.
Boron‐Doping of a Macrocyclic Tetrafuran Framework Unveils an Expanded Porphyrinoid With Switchable (Anti)Aromaticity and Conformational Dynamics
ABSTRACT Expanded porphyrinoids are an emerging class of organic chromophores with often exceptional optoelectronic properties such as broad absorption extending into the near‐infrared (NIR) spectral region. To optimize porphyrinoid‐based materials for specific purposes, it is essential to specifically tailor their electronic properties. This can be achieved by incorporation of heteroatoms into their π‐conjugated framework. Replacing C atoms of their backbone with trivalent boron centers yields electroneutral boraporphyrinoids that feature a reduced π‐electron count compared to their carbon analogs. While some thiophene‐based boraporphyrinoids have been reported, boron macrocycles based solely on the renewable furan building block have remained elusive so far. Herein, we present the unprecedented diboratetraoxaporphyrin(2.1.2.1) 1E and the potassium salt of its dianion K 2 [1E] , as well as open‐chain reference compound 6 . Investigation of the electronic structure of 1E , [1E] 2− , and the radical anion [1E] •− revealed that 1E exhibits magnetically antiaromatic features that are more pronounced compared to its thiophene analog diboratetrathiaporphyrin(2.1.2.1), while upon transition to [1E] 2− it becomes strongly aromatic. Interestingly, neutral porphyrinoid 1E is conformationally flexible, while the macrocyclic backbone becomes rigid upon reduction to K 2 [1E] . The aromatic porphyrinoid K 2 [1E] has absorption bands in the blue, red, and NIR spectral regions and exhibits photoluminescence at 1032 nm.
Thiolated Polymers in 3D Bioprinting: Control of Gelation
ABSTRACT Thiolated polymers represent a versatile class of bioinks for extrusion‐based 3D bioprinting, combining cytocompatibility with tunable crosslinking chemistry and dynamic redox‐responsive behaviour. This review consolidates recent advances in thiomer chemistry, focusing on synthetic strategies that modulate thiol reactivity through pKa adjustment, neighboring‐group interactions, and redox control. Crosslinking mechanisms such as oxidative disulfide formation, thiol–ene, thiol‐yne, and thiol‐polyphenol reactions are compared in terms of their impact on gelation. External triggers, including small‐molecule and polymeric crosslinkers, light activation, oxidants, enzymatic systems, as well as hybrid dual‐stage systems, are discussed for their capacity to achieve controlled gelation and long‐term stability. A comprehensive printability framework links chemical design to performance metrics such as gel point, modulus build‐up rate, collapse angle, filament fusion index, fidelity ratio, and shear thresholds that maintain cell viability. Redox‐driven reversibility provides additional adaptability through self‐healing and stress‐relaxation mechanisms. Applications span soft tissue and cartilage regeneration, vascularized and multicellular constructs, hemostatic adhesives, and extracellular matrix–mimetic scaffolds for stem‐cell culture. These developments collectively establish design principles for balancing gelation kinetics, shape fidelity, and biological functionality in thiomer‐based bioinks.
Tailored Vapor Deposition Unlocks Large‐Grain, Wafer‐Scale Epitaxial Growth of 2D Magnetic CrCl <sub>3</sub>
ABSTRACT Two‐dimensional magnetic materials (2D‐MM) are an exciting playground for fundamental research, and for spintronics and quantum sensing. However, their large‐grain, wafer‐scale synthesis using scalable vapor deposition methods is still an unsolved challenge. Here, a tailored physical vapor transport deposition (PVTD) method is developed, which enables centimeter‐scale, epitaxial growth of semiconducting 2D‐MM CrCl 3 at 500°C (on mica substrate). A controlled synthesis protocol, enabled via four process innovations, (i) low emissivity secondary heating source, (ii) very‐high carrier‐gas flow, (iii) dynamic precursor flux control, and (iv) oxygen/moisture removal, suppresses redox etching and drives growth beyond the diffusion limit for wafer‐scale growth. Optical, stoichiometric, structural, and magnetic characterization confirm single‐crystalline, phase‐pure 2D‐MM CrCl 3 . Substrate temperature tunes thickness of films from few‐layers to tens of nanometers, while flow rate controls nucleation density and coverage. Further, we demonstrate selective‐area growth and large‐area transfer, validating potential wafer‐level device integration. Substrate‐dependent growth features are explained using density functional theory and state‐of‐the‐art machine learning interatomic potential‐based atomic‐scale simulations. This scalable, flexible vapor deposition approach offers a general route for synthesizing several (volatile and reactive) 2D‐MM and bridges the scalability gap from conventional wafer‐scale materials. The low‐temperature growth will enable the creation of hybrid functional heterostructures.
Survival impact of post-transplant tyrosine kinase inhibitor therapy in chronic myeloid leukemia.
e18599 Background: Although tyrosine kinase inhibitors (TKIs) have reduced the need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia (CML), transplantation remains necessary for patients with TKI resistance, intolerance, or disease progression. Post-transplant TKI maintenance is widely used, yet real-world data evaluating its impact on overall survival (OS) and graft-versus-host disease (GVHD) are limited. We assessed the association between post-HSCT TKI use and long-term survival and GVHD outcomes. Methods: Adult CML patients undergoing allo-HSCT between January 2010 and June 2025 were identified in the TriNetX Research Network and categorized by TKI exposure within 3 months post-transplant. Cohorts were propensity score matched 1:1. OS was evaluated using Kaplan–Meier and Cox regression for 3 and 5 years. A landmark analysis beginning on day 30 was performed to address immortal time bias. Secondary outcomes included chronic GVHD within 1 year. Results: After matching, 350 patients were included (175 TKI vs 175 no TKI). At 3 years from transplant (day 0), OS was significantly higher with TKI therapy (72.67% vs 58.90%; HR 0.57, 95% CI 0.389–0.837; log-rank p=0.0036), with consistent landmark results (73.51% vs 59.93%; HR 0.566, 95% CI 0.383–0.838; p=0.0040). At 5 years, OS remained superior (68.75% vs 55.31%; HR 0.588, 95% CI 0.407–0.851; p=0.0043), with similar landmark findings (69.55% vs 56.27%; HR 0.585, 95% CI 0.402–0.853; p=0.0048). Chronic GVHD within 1 year was more frequent among TKI-treated patients (37.14% vs 24.57%; OR 1.81, 95% CI 1.14–2.88; p=0.011). Conclusions: Post-transplant TKI therapy was associated with significantly improved 3- and 5-year OS in patients with CML undergoing allo-HSCT, including landmark analysis. Higher rates of chronic GVHD may reflect confounding by indication and longer survival rather than a direct causal effect. These findings support post-HSCT TKI maintenance as an important survival-enhancing strategy in CML.
Epidemiology of oral cavity cancer in women: Identifying the highest-risk age group.
e22594 Background: Oral cavity cancer has historically been more prevalent in men, largely attributed to tobacco use, alcohol consumption, and human papillomavirus (HPV). Emerging data however, suggest shifting patterns and a rising disease burden among women. This study aims to identify the female age groups most at risk for malignancy. Methods: We conducted a retrospective, population-based analysis using data from the Surveillance, Epidemiology, and End Results (SEER) Program, Registry 17, which captures approximately 48% of the U.S. population and includes information on patient demographics and tumor characteristics of various malignancies. In our analysis, female patients diagnosed with oral cavity cancer between 2000 and 2022 were included. Cases were stratified by age group, and age-adjusted incidence rates were calculated for each group using SEER*Stat software for two time periods: 2000–2010 and 2011–2022. Trends within each age group were assessed using annual percent change (APC) estimates with 95% confidence intervals (CI). APCs were considered significant if the CI did not include zero. Analyses were further stratified by tumor behavior (malignant versus non-malignant) to identify contributors to observed trends. Results: Females aged 60 years and older disproportionately contributed to the increase in oral cavity cancer incidence from 2000 to 2022. A statistically significant rise was observed in this age group from 2010 to 2022 (APC 0.4; CI 0.1-0.7; p < 0.05) compared with 2000–2010 (APC 0.2; CI -0.4-0.7). In contrast, women younger than 60 years did not demonstrate a statistically significant change in incidence over the same period (APC 0.4; CI: −0.2–0.5). When stratified by tumor behavior, the increase in incidence among women aged 60 years and older was driven primarily by invasive oral cavity cancers (APC 0.4; CI: 0.1–0.8; p < 0.05). In contrast, benign lesions did not demonstrate statistically significant contribution to this trend (APC 0.7; CI -0.7 - 2.1). Detailed age-stratified APC estimates are shown in Table 1. Conclusions: This analysis demonstrates a growing burden of invasive oral cavity cancer among women aged 60 years and older. While prior SEER analyses have suggested this trend exists for women aged 50–64 years, our findings refine this observation to females older than 60 and invasive cancers as primary drivers. This suggests potential gaps in early detection or evolving risk factors in older women and underscores the need for age-targeted screening and prevention strategies. APC of oral cavity cancer among women by age group. Age 2000-2010 APC 95% CI 2011-2022 APC 95% CI <40 0.7 -0.7-2.1 -0.5 -1.6-0.6 40-49 -0.6 -1.5-0.3 -1.4** -2.0- -0.8 50-59 0.7** 0.4-1.0 -0.6** -1.2- -0.1 60-69 0.5 -0.1-1.1 0.8** 0.2-1.4 70+ 0.2 -0.4-0.8 1.1** 0.5-1.7 <60 0.4 -0.1-0.9 0.1 -0.2-0.5 >60 0.2 -0.4-0.7 0.4** 0.1-0.7 **Indicates statistically significant p-value < 0.05.
Five-year follow-up of neoadjuvant chemoimmunotherapy in locally advanced head and neck squamous cell carcinoma.
6102 Background: Neoadjuvant chemoimmunotherapy has shown high rates of pathological response in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, its long-term survival outcomes, the predictive value of pathological complete response (pCR), and patterns of late failure remain unclear. Methods: In this single-arm phase II trial, 30 patients with resectable LA-HNSCC received three cycles of nab-paclitaxel (or docetaxel) plus cisplatin and camrelizumab, followed by surgery and adjuvant radiotherapy. The primary endpoint was pCR rate. With follow-up until January 2026, the median follow-up was 60 months. Analyses included overall survival (OS), recurrence patterns, and incidence of second primary tumors. Results: The pCR rate was 37.0% (10/27). Key Finding 1: This study represents the first report of 5-year long-term survival data for this regimen, with a 5-year OS rate of 76.7%. Key Finding 2: None of the patients who achieved pCR and completed adjuvant radiotherapy experienced local recurrence (0/7), whereas the recurrence rate was 33.3% (1/3) among those who did not receive radiotherapy, underscoring the role of radiotherapy even in pCR patients. Key Finding 3: Six patients (20%) developed second or third primary tumors during long-term follow-up (sites included larynx, esophagus, and lung), with incidence increasing over time. Key Finding 4: Two patients developed osteoradionecrosis of the jaw more than two years after radiotherapy, leading to malnutrition and subsequent death, highlighting the importance of long-term toxicity management. Conclusions: Neoadjuvant chemoimmunotherapy provides durable survival benefit in LA-HNSCC. pCR is associated with minimal local recurrence. However, with prolonged survival, the risk of second primary tumors becomes significant, and late radiation toxicities can impact outcomes. These findings emphasize the need for establishing lifelong surveillance protocols for multiple primary cancers and systematic management of late toxicities in this population. Clinical trial information: ChiCTR1900025303.