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Scanxiety: Patient experience of immediate result release (IRR) of cancer-related imaging.

e13583 Background: The 21 st Century Cures Act, signed in 2016, requires immediate result release (IRR) of labs and imaging results to patients. Patients often receive these results without their providers, raising concerns about “scanxiety” - worry experienced while awaiting or interpreting scan results. A better understanding of scanxiety and patient risk factors can inform targeted interventions to improve patient experience with IRR. Methods: We used a subset of questions from two validated questionnaires, the Impact of Events Scale-Revised and the Fear of Cancer Recurrence – Short Form, to construct a 49-question cross sectional patient survey. We administered the questionnaire to assess cancer-related worry (defined as the cognitive component of anxiety) in patients seen in a multi-site academic Gastrointestinal Oncology clinic in metropolitan New York City between 11/28/23 and 4/25/24. We calculated descriptive statistics for extent of worry. We also analyzed patient demographic and clinical characteristics for associations with worry outcomes. Results: We received 218 responses for an estimated 10% response rate. Responses to most questions were on a 0-4 Likert scale. A total of 105 women (49.5%) and 106 men (50%) responded to the survey, with a median age of 67. Overall, patients reported greater worry regarding possible recurrence or progression of their cancer (composite mean = 2.54, standard deviation = 0.20) as opposed to worry related to their most recent imaging (1.38, 0.27) (p < 0.001). There was a moderately strong positive correlation between baseline worry over cancer progression/recurrence and image-related worry (Pearson’s r = 0.56, 95% confidence interval: 0.46, 0.65). Gender was found to have a significant association with image-related worry frequency (β = 0.46, p = 0.01) and impact of worry on daily functioning (β = 0.58, p < 0.001) with women experiencing greater frequency and impact of worry than men. We found a significant association between age and worry frequency, with each additional decade of age corresponding to a decrease in worry frequency (β = –0.20, p = 0.006). We also found increased patient self-rated confidence in interpreting medical imaging to be inversely associated with worry frequency (β = -0.18, p = 0.02) and impact (β = -0.16, p = 0.02). Notably, cancer stage, marital status, and reason for imaging (surveillance, treatment response, or symptom investigation) were not associated with worry. Conclusions: Overall, we found that patients do worry about cancer-related imaging, albeit less than about disease recurrence and progression. Higher baseline worry about cancer recurrence/progression, female sex, younger age, and lower self-rated confidence in reviewing medical imaging were all positively associated with cancer imaging–related worry. Our research can help to focus interventions on groups at highest risk of scanxiety from early on in their cancer care.

OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy with regulatable membrane-bound IL15 (mbIL15) in patients with advanced melanoma that has progressed on/after immune checkpoint inhibitors (ICI): Phase 2 results.

9507 Background: OBX-115 TIL are engineered to express mbIL15 under regulatory control of the small-molecule drug acetazolamide (ACZ); this engineering abrogates the need for toxic high-dose IL2 cytokine support after TIL infusion. Early data demonstrated differentiated safety and promising efficacy at the recommended phase 2 dose (RP2D; Chesney ASCO 2025). We report additional data evaluating OBX-115 in patients (pts) with advanced melanoma treated at the RP2D in the Agni-01 study. Methods: This single-arm, open-label, phase 1/2 study (NCT06060613) assesses safety, tolerability, and efficacy of the OBX-115 TIL cell therapy regimen in pts with advanced non-uveal melanoma and NSCLC (Shoushtari AACR 2025); eligibility was not restricted by LDH, HLA, or melanoma subtype. Phase 1 established an RP2D of OBX-115 1–100×10 9 cells, with ACZ 500 mg/d orally on Days 0–6 (Wk 1) and 14–20 (Wk 3). Phase 2 evaluates efficacy of the regimen at RP2D by RECIST v1.1 per investigator in pts with ≤2 prior lines of therapy. OBX-115 is manufactured from pt tumor tissue (core needle biopsy [CNB] or surgical excision) and infused after low-dose (Cy 750 mg/m 2 /d × 3; Flu 30 mg/m 2 /d × 4) lymphodepletion (LD). ACZ is redosed (7 d) after recovery from LD every 6 wks until Wk 24. Primary data cutoff is 19Dec2025; RECIST efficacy was updated on 22Jan2026. Results: OBX-115 was successfully manufactured (median dose 83.4×10 9 cells) and infused at RP2D schema for 15 pts with advanced melanoma progressing on/after ICI (doublet ICI in 93%); 6/8 pts (75%) with BRAF-mut disease had prior BRAF-/MEK-inhibitor exposure. 2 pts (13%) had tumor tissue procurement by CNB; 4 pts (27%) received outpatient LD. Confirmed ORR was 67% (1 CR, 9 PR, 4 SD; DCR 93%). At median study follow-up of 18.6 wks (range 10.1–73.4), median duration of response was not reached (range 4.6+ to 55.1+ wks). There was no dose-limiting toxicity, ICU transfer, or treatment-related mortality. Immune-related adverse events (AEs) included CRS (G3 n=1; G<3 n=4) and hypoxia (G3 n=1; G<3 n=2), which responded to short-course steroids; no ICANS was observed. 3 pts reported 4 OBX-115–related serious AEs. 13 pts were alive as of the datacut. Conclusions: OBX-115 TIL cell therapy at RP2D demonstrated encouraging efficacy in 2/3L advanced non-uveal melanoma, an area of unmet medical need. Unique aspects of the OBX-115 regimen, such as low-dose LD, ACZ-inducible mbIL15 expression, and CNB-enabled manufacturing, were associated with manageable side effects and compare favorably with other adoptive TIL approaches. Data support continued investigation of OBX‐115 in the ongoing phase 2 portion of Agni-01 and planned registrational study. Clinical trial information: NCT06060613 .

Precision Promise (PrP): Success rates of paired biopsies and biomarker testing results for metastatic pancreatic cancer (mPDAC) in a multi-center trial.

4196 Background: PrP, a phase 2/3 Bayesian adaptive platform trial sponsored by the Pancreatic Cancer Action Network, was developed to test multiple experimental arms efficiently against common controls and explore biomarkers of response/resistance in mPDAC (Picozzi, ASCO TPS 4188, 2022). Methods: At screening, core tissue biopsies and matched blood collection were performed for first- and second-line patients (pts) with mPDAC. Week 8 (W8) core tissue biopsies and blood collection were performed for pts receiving study drug. Formalin-fixed paraffin embedded (FFPE) tissue slides were prepared at the central lab; tissue and matched blood samples were analyzed for genomic and transcriptomic analyses using Tempus xT (DNA) and xR (RNA) testing, respectively. The workflow prioritized DNA followed by RNA isolation. Results: Tissue biopsies were obtained at screening from 491 of 700 (70%) pts across 24 US sites; W8 tissue biopsies were obtained from 228 of 443 (51%) pts receiving study drug. Reasons for biopsies not being collected included: contraindicated; attempted, but no tissue obtained; pt screened out; pt stopped study drug before W8 (W8 only). 21% (103/491) screening and 32% (74/228) W8 biopsies submitted for biomarker testing contained insufficient tumor tissue for testing; 4% (20 pts) of screening and 4% (10 pts) of W8 biopsies were not processed into FFPE or testing was cancelled. Of the 368 pts with screening tissue sequenced, genomic data were generated for 83% (304 pts); 17% (64 pts) had Quantity Not Sufficient (QNS) for DNA. Transcriptomic data were generated for 49% (179 pts); in 42% (155 pts) insufficient tumor tissue remained for RNA testing and 9% (34 pts) had QNS for RNA. Of the 144 pts with W8 tissue sequenced, genomic data were generated for 71% (102 pts); 29% (42 pts) had QNS for DNA. Transcriptomic data were generated for 31% (44 pts); in 58% (84 pts) insufficient tumor tissue remained for RNA testing and 11% (16 pts) had QNS for RNA. Locations of tissue biopsies across both timepoints (719) were: 68% liver, 16% pancreas, 16% other metastatic sites. Success rates for biomarker testing across all tissue obtained was higher for liver metastases (65% DNA results; 37% RNA results) than for primary tumors in the pancreas (42% DNA results; 19% RNA results). Distribution of actionable biomarkers detected will be presented. Conclusions: These data demonstrate success rates of paired biopsy acquisition and subsequent genomic and transcriptomic analysis in a large phase 2/3 multi-center platform trial for mPDAC. Attrition was noted for biopsy collection and downstream biomarker testing at screening and more so at W8 on study drug. Biomarker testing success rates varied by tissue location. These findings along with planned data interrogation and future sample analyses will provide insights to guide future trial design and clinical decision making. Clinical trial information: NCT04229004 .

Results from a phase 2a study of atebimetinib in combination with mGnP in advanced or metastatic pancreatic cancer.

4013 Background: Pancreatic ductal adenocarcinoma (PDAC) is driven predominantly by oncogenic KRAS signaling, yet prior attempts to target the MAPK pathway have been limited by toxicity and emergence of resistance. Atebimetinib is a next-generation, deep cyclic inhibitor (DCI) of MEK designed to achieve pulsatile pathway inhibition with improved tolerability. We report a Phase 2a cohort evaluating atebimetinib in combination with modified gemcitabine/nab-paclitaxel (mGnP) in the first-line treatment of advanced or metastatic PDAC (NCT05585320). Methods: In this multicenter, open-label, nonrandomized Phase 2a study, patients with previously untreated advanced or metastatic PDAC were eligible for participation and were treated with orally administered atebimetinib daily in combination with mGnP (modification: every other week dosing). The primary endpoint was objective response rate (ORR) per investigator assessment using RECIST 1.1 criteria in response-evaluable patients. The cohort was powered (~80%, one sided alpha 0.05) using an optimal Simon’s 2-stage design. Results: Fifty-five patients were enrolled and treated with 320 mg atebimetinib daily + mGnP. ECOG performance status was 0-1 (100%); median age was 68 years (range 42-85 years), 62% were ≥65 years, and 55% were male. No grade 5 treatment-related adverse events (AE) were observed. No AE related to atebimetinib were higher than grade 3. Grade 3 AE related to atebimetinib occurred in 29% of participants, with the most frequent being rash (5%), ALT increased (5%), and AST increased (5%). Among the 50 response-evaluable patients, best overall response (BOR) achieved were 21 PR, 21 SD, 7 PD, 1 NE. The ORR was 42%, and DCR was 84%. With a median follow-up of 10.4 months (data cutoff Jan 7, 2026), 6- and 9-month OS rates were 88% and 79%, respectively; median PFS was 8.3 months and median OS was not reached. Conclusions: Atebimetinib in combination with mGnP demonstrated favorable safety and promising efficacy compared to historic standard-of-care (SoC) GnP. 1 A phase 3 registrational trial is planned to start in mid-2026 for evaluation of atebimetinib + mGnP versus SoC GnP. 1. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med . 2013;369(18):1691-1703. doi:10.1056/NEJMoa1304369 (PMID: 24131140). Clinical trial information: NCT05585320 .

Stage I results of a phase II study evaluating thymosin α1 combined with toripalimab in elderly patients with advanced melanoma.

9554 Background: Anti–PD-1 monotherapy yields limited response rates in Chinese patients with melanoma, highlighting the need for effective combination strategies. Elderly patients frequently present with multiple comorbidities and immunosenescence which may compromise both the efficacy and safety of immunotherapy. Thymosin α1 (Tα-1) promotes T-cell activation and survival, potentially enhancing responsiveness to immunotherapy, while exerting immunomodulatory effects during excessive inflammation that may reduce the risk of immune-related adverse events (irAEs). This study aimed to evaluate whether combining Tα-1 with toripalimab could improve efficacy while mitigating irAEs in elderly patients with advanced melanoma. Methods: This was a single-arm, open-label, Simon two-stage phase II study. Patients aged ≥60 years with pathologically confirmed unresectable stage III or IV melanoma and no prior immune checkpoint inhibitor exposure were enrolled. Treatment consisted of Tα-1 (1.6 mg daily during week 1, then three times weekly during weeks 2–3) plus toripalimab 240 mg intravenously every 3 weeks for up to four cycles, followed by toripalimab maintenance until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Stage I required ≥3 responses among 19 evaluable patients to proceed to Stage II. Results: Between July 2023 and September 2025, 19 patients were enrolled (median age 72 years, range 60–81). Acral melanoma accounted for 78.9% (n=15). All patients had chronic comorbidities; 63.2% had ECOG ≥2 and 47.4% had metastases in ≥3 organs. At a median follow-up of 10.5 months, ORR was 47.3% (95% CI, 22.6–72.1). Median PFS was 8.0 months (95% CI, 4.4–11.6), and median OS was not reached. Median PFS was 8.1 vs. 4.5 months in acral versus non-acral cutaneous melanoma (P=0.4). Elevated LDH showed a trend toward shorter PFS (2.8 vs. 8.1 months, P = 0.076). Six grade 1 irAEs were observed (vitiligo n=2, transaminase elevation n=2, thyroiditis n=2). Patients without progressive disease had lower neutrophil-to-lymphocyte ratios and higher lymphocyte percentages than those with PD. Conclusions: Tα-1 combined with toripalimab demonstrated promising efficacy and excellent tolerability in elderly patients with advanced melanoma. The prespecified criteria for Stage II expansion were met, and enrollment of an additional 36 patients is ongoing. Patient demographics. Characteristics No. of Patients (N=19) Age (median, range 72 (60-81) Male (%) 8 (42.1%) Melanoma subtype Acral 15 (78.9%) Cutaneous 4 (21.1%) NRAS status Wild type 14 (73.7%) Mutation 4 (21.1%) unknown 1 (5.3%) No. of organs with metastasis ≥3 9 (47.4%) Liver metastasis Yes 4 (21.1%) No 15 (78.9%) Brain metastasis Yes 2 (10.5%) No 17 (89.5%) ECOG PS 1 7 (36.8%) ≥2 12 (63.2%)

Dynamic biological and metabolic response by EBV DNA and ¹⁸ F-FDG-PET-CT to induction chemotherapy (IC) to enhance prognostication in endemic nasopharyngeal carcinoma (NPC).

6112 Background: IC followed by concurrent chemoradiotherapy (CCRT) is the current standard of care for locoregionally-advanced NPC (LA-NPC). Nonetheless, evidence suggests that IC response is a strong predictor for risk of relapse in LA-NPC. Here, we characterized the dynamic metabolic and biological responses to IC, and investigated their associations with survival in patients with high-risk LA-NPC. Methods: Newly diagnosed patients with non-metastatic, biopsy-proven NPC were enrolled into two prospective ongoing studies (NCT04340024 and NCT06093061). For this analysis, patients who received 2-3 cycles of gemcitabine-cisplatin/carboplatin IC were included; all patients had plasma EBV DNA assessed following every IC cycle, and 18 F-FDG-PET-CT performed pre-IC and 1 week before the end of IC. For the latter, standardized uptake values (SUVs) were recorded for the primary tumor (SUVp) and individual nodal lesion(s) (SUVn). Biological (bCR) and metabolic complete response (mCR) were defined as EBV DNA =0 copy/mL and SUV ≤2.5, respectively. Prediction accuracy of 2y disease-free survival (DFS) was assessed by area under the receiver operating characteristic curve (AUC). Results: 117 patients diagnosed between Jan 2019 to Apr 2025 were included in this analysis; of these, 112 and 106 had SUVp and SUVn at pre- and post-IC. For SUVn, we performed lesion-level analysis for 259 LNs. Median follow-up was 20.5 (interquartile range [IQR]: 11.6-41.3) mo and TNM-8 stage distribution for stage III and IVA were 43% (50/117) and 57% (67/117), respectively. Median SUVp and SUVn pre-IC were 15.0 (IQR: 10.4-18.2) and 8.5 (IQR: 4.5-12.3), respectively, while median EBV DNA level was 4800 (IQR: 914-20598) copies/mL. Post-IC, we recorded mCR at the primary tumor and LNs for 33/112 (29%) and 49/106 (46%), respectively; while 14/117 (12%), 30/117 (26%) and 40/117 (34%) patients manifested bCR post-IC1, IC2, and IC3, respectively. Metabolic response was not correlated with biological response; of 33 patients with primary tumor mCR, 20/33 (61%) had bCR; while for LNs, only 25/49 (51%) patients with mCR manifested bCR post-IC. Additionally, we observed significant intrapatient heterogeneity of mCR between LN lesions post-IC; in 57/106 patients with non-mCR for ≥1 of the LNs, SUVn ranged between 0-12.9. Finally, incorporating both post-IC bCR and mCR to TNM-8 stage and pre-IC EBV DNA enhanced AUC of 2y DFS prediction; from 0.58 (95%CI:0.44-0.73) [TNM-8+pre-IC EBV DNA] to 0.77 (95%CI:0.60-0.94). Conclusions: Metabolic and biological responses to IC provide unique information on response phenotypes of patients with LA-NPC, and improved the prediction accuracy of 2y DFS compared with TNM-8 stage and pre-IC EBV DNA. Combinatorial 18 F-FDG-PET-CT and EBV DNA post-IC may enhance the selection of these patients for treatment intensification.

Don't smoke the odds: Improving lung cancer screening among current smokers in East Texas.

e23286 Background: Lung cancer has been the leading cause of cancer death in the United States for over 70 years. Approximately 85-90% of patients with lung cancer are current or former tobacco users. The guideline for lung cancer screening is unique in that it is correlated to a preventable risk factor: tobacco use. Since March 2021, the United States Preventive Service Task Force (USPSTF) has recommended lung cancer screening for adults 50-80 years with at least a 20-pack-year smoking history who currently smoke or have quit within 15 years. Our quality improvement project was designed to increase screening in tobacco users in East Texas, thereby increasing patients who are appropriately screened for lung cancer. Methods: Our residency clinic at CHRISTUS Health in Longview, TX uses EPIC as its electronic medical record (EMR), which includes SmartSets that combine orders to streamline patient care. We added a reminder on the “Tobacco/E-cig/Vaping Cessation” SmartSet to use the “Lung Cancer Screening” SmartSet to order low-dose CT scans based on USPSTF criteria. Residents were educated about the updates and importance of utilizing both SmartSets in February 2025. Baseline differences (Table 1) were assessed using two proportion z tests, comparing our clinic (Long Resident Clinic) to other CHRISTUS clinics over one year. We used a generalized linear mixed model (GLMM) since screening practices may vary across clinics. We hypothesized an increase in screening by at least 5% by the end of 2025. Results: Our clinic’s baseline screening rate was 52%, compared with 41.7-44.6% at other clinics with differences statistically significant across all clinics (p < 0.03, BH-adjusted p < 0.05). Screening rates at our clinic increased, reaching 63% by December 2025; the GLMM showed a statistically significant positive time effect. The intervention was associated with higher screening odds (OR=1.67, 95% CI: 1.49-1.88). Conclusions: Embedding the USPSTF guidelines within the SmartSet increased appropriate low-dose CT screening by identifying tobacco users and adherence to screening criteria. Furthermore, our findings support integrating point-of-care EMR prompts as an effective strategy to close screening gaps, standardize evidence-based practice, and facilitate early detection of lung cancer in vulnerable populations. This strategy can be used among high risk patients across health systems to positively impact morbidity and mortality. Baseline two sample tests of proportions (Long Resident Clinic vs other regional clinics). Comparison clinic LRC rate 1 Other rate Diff. (pp) 2 p-value BH-adjusted p 3 Long Internal Medicine 0.520 0.430 9.0 0.0177 0.0237 Longview/Marshall Primary Care 0.520 0.446 7.4 0.0253 0.0253 CTC Primary Care 0.520 0.443 7.7 0.0152 0.0237 SPN Fam Med Academic 0.520 0.417 10.3 0.0110 0.0237 1 Long Resident Clinic. 2 Difference in percentage points. 3 p-values adjusted using the Benjamini–Hochberg method.

Screen failures among patients who consented for early phase cancer clinical trials (EPCTs).

e23013 Background: EPCTs represent an important treatment option for patients with cancer. However, trials often have strict eligibility criteria and screen failures (SFs) can limit enrollment. We sought to identify reasons for SFs among potential EPCT participants, evaluate associations between SFs and overall survival (OS), and describe use of supportive care services and subsequent therapies among patients with SFs. Methods: Using an institutional EPCT database, we identified adult patients who signed consent for an EPCT between 1/2021 – 10/2025 but did not receive treatment on the trial. We retrospectively reviewed the electronic health record to obtain patient demographics, clinical characteristics, reasons for SFs, receipt of palliative care (PC), advanced care planning (ACP), future therapies, and OS. Results: Table 1 provides the reasons for SFs. Among 273 identified patients (median age = 64.1 years [range 18.4 – 90.2], 52% female), most common reasons for SFs were clinical decline (CD; 28%) and lab abnormalities (19%); 6% with unknown reason were excluded from table. Patients with CD had increased risk of death (HR 2.3, p < 0.0001) compared to other reasons for SF, while those with SFs due to patient preference and lack of measurable disease had longer survival (HR 0.4, p = 0.001; HR 0.2, p < 0.0001); see Table 1 for OS results. Among all patients, median OS was 3.9 months (95% CI 3.3 – 5.1) and median follow up was 26.1 months (95% CI 22.9-29.8). Most patients (66%) were referred from within the hospital system and nearly half (48%) had received 3+ lines of therapy; 30% had participated in a prior EPCT. Among internal referrals, the majority did not have prior PC (70%), ACP documentation (70%), or advance directive (92%). Most patients (64%) received another line of therapy after SF, including 11% who enrolled on another EPCT. Of those with CD, 49% pursued hospice/supportive care, 36% received another line of therapy, and 11% died during screening. Conclusions: Reasons for SFs are varied, with CD as the most common. We found that most patients had no prior PC receipt or ACP documentation, despite having advanced disease and receiving multiple prior lines of therapy. Notably, most patients received further therapies and some experienced extended survival. Further work is needed to better understand and address reasons for SFs to improve care for this population. Reason for SF N (%) Median OS (months, 95% CI) OS HR (95% CI) P Clinical decline 76 (28) 1.6 (1.2 - 5.6) 2.3 (1.7 - 3.1) <.0001 Lab abnormality 52 (19) 3.9 (2.2-7.8) 1.1 (0.8-1.6) .450 Patient preference 28 (10) 20.2 (3.4 - NR) 0.4 (0.3 - 0.7) .001 Multiple reasons 23 (8) 2.7 (1.3 - 4.0) 1.4 (0.9 - 2.3) .148 New CNS disease 22 (8) 3.9 (2.5 - 6.3) 1.3 (0.8 - 2.1) .248 Comorbidity 19 (7) 6.3 (3.9 - NR) 0.7 (0.4 - 1.2) .221 Trial logistics 14 (5) 6.0 (2.6 - 11.7) 0.9 (0.5 - 1.5) .587 Medication interaction 12 (4) 11.2 (2.1 - NR) 0.6 (0.3 - 1.3) .179 No measurable disease 11 (4) NR (14.0 - NR) 0.2 (0.1 - 0.5) <.0001

Comparing the rates of hypersensitivity reactions in patients undergoing first-dose taxanes utilizing fixed-rate vs. stepwise-titration infusions.

e24165 Background: Taxanes are associated with a higher incidence of immediate hypersensitivity reactions (HSRs) compared to other classes of chemotherapeutic agents, even with adequate premedication. This study evaluates whether a titrated infusion protocol reduces the rate of first-dose HSRs to taxanes. Methods: This was a retrospective cohort study conducted at a single site hematology/oncology infusion center. The fixed-rate arm consisted of patients from January 2022 to July 2023 who received a fixed infusion rate for their first dose. The titration arm comprised patients from August 2023 to July 2024 who underwent a three-step titration protocol for their first dose. The primary endpoint was the rate of immediate HSRs during the first lifetime dose of docetaxel or paclitaxel. Secondary endpoints included HSR severity, HSRs during the first or second dose, and rate of treatment discontinuation due to HSRs. Results: Of 479 patients included (240 fixed-rate; 239 titration), HSRs occurred in 7.1% of the fixed-rate group and 11.3% of the titration group (OR 1.67, 95% CI 0.89-3.15; p= 0.1104). There were no differences in the severity of HSRs or in the rate of treatment discontinuation among both groups. Conclusions: The use of a titrated infusion protocol for first lifetime dose taxanes did not significantly reduce the incidence or severity of immediate HSRs. These findings suggest that a titration protocol may not confer additional benefits over fixed-rate in this setting. Primary and secondary endpoints. Fixed (N=240) Titration (N=239) OR 95% CI p-value Primary Endpoint Rates of immediate HSR 17 (7.1%) 27 (11.3%) 1.67 0.89- 3.15 0.110 Secondary Endpoints Severity of immediate HSR N=17 N=27 Grade 1 10 (58.8%) 8 (30.8%) 0.637 Grade 2 6 (35.3%) 12 (46.2%) 0.157 Grade 3 1 (5.9%) 6 (23.1%) 0.059 Rates of immediate HSR with first or second dose combined N=471 infusions N=453 infusions 26 (5.5%) 37 (8.2%) 1.52 0.91-2.56 0.111 Taxane administration time (min) N=239 N=232 1-hour infusion 71.8 92.8 3-hour infusion 187.6 201.6 Rates of medication discontinuation due to immediate HSR N=26 N=37 1 (3.8%) 8 (21.6%) 6.90 0.81-59.17 0.069

A phase Ia/Ib trial of FAP-Dox (AVA6000), a fibroblast activation protein (FAP)–released doxorubicin peptide drug conjugate in patients with FAP-positive solid tumors and activity against salivary gland cancers.

e15113 Background: Faridoxorubicin (faridox, AVA6000) is a cleavable peptide drug conjugate (PDC) comprised of doxorubicin (dox) bound to a peptide by a linker that is specifically cleaved by FAP, which is overexpressed in the tumor microenvironment (TME) of many solid tumors. This PDC technology utilizes a mask and release technology to concentrate released payload in the TME. Methods: The safety, pharmacokinetics (PK) and preliminary efficacy of faridox were established in a first-in-human, multicenter Phase 1a and 1b trial with faridox administered i.v. q3w or q2w using a 3+3 design in patients with locally advanced or metastatic solid tumors. The Phase 1b expansion portion enrolled patients with salivary gland cancer (SGC), soft tissue sarcoma (STS) and triple negative breast cancer (TNBC) patients at the Phase 1a RP2D of 310 mg/m 2 Q3W. AUC based dosing was initially utilized to calculate maximum safe number of cycles of AVA6000, equivalent to a cumulative dox dose of 550 mg/m 2 ; this lifetime limit was lifted during Phase 1b based on absence of cardiac toxicity. Results: Results of the faridox Phase 1a escalation in 63 patients were previously reported (Lahu et al, ESMO 2025). In the Phase Ib expansion portion, an additional 27 patients with SGC, TNBC or STS have been dosed as of the data cutoff (median age 62 yr, range 32-81; 44% male; 63% ECOG 0). The safety profile in Phase Ib was favorable and consistent with Ph Ia observations; the most frequent AEs being fatigue (56%), alopecia (52%), nausea (44%), anemia (26%), and neutropenia (22%). Grade 3-4 hematologic toxicities included neutropenia (11%) and lymphopenia (4%). No grade 3 or 4 cardiac events or clinically relevant changes in left ventricular ejection fraction were observed despite faridoxorubicin being dosed to dox exposures associated with a cumulative dose of 550 mg/m 2 . Based on the favorable cardiac safety data, the lifetime maximum dox exposure was lifted during the trial. Compared to conventional dox, PK showed reduced systemic exposure (AUC, up to 77% reduction), reduced volume of distribution and higher tumor concentrations (median 117:1 ratio of tumor to plasma exposure of released dox). In the 30 patients with SGC treated across Phase 1a and 1b (n = 11 and 19), 2 pts with partial responses and 25 pts with stable disease were observed for a disease control rate of 90%. Median PFS in the SGC cohort has not been reached with median follow up exceeding 5 mos in the combined cohort (9 mos in Ph Ia). Efficient dox production was observed in the TME with FAP IHC levels ranging from 1+-3+ by immunohistochemistry in SGC. Conclusions: Faridox is active in SGC and well tolerated, delivering high concentration of free dox to the TME relative to plasma. Responses were observed and prolonged disease stabilization in patients with SGC indicating activity of the PDC. Clinical trial information: NCT04969835 .

Photo‐Tautomerization‐Driven Energy Transfer at the Hole‐Transport Interface Stabilizes Efficient Inverted Perovskite Solar Cells

ABSTRACT Perovskite solar cells (PSCs) offer high power conversion efficiencies (PCEs) but suffer from UV‐induced degradation, hindering their practical deployment. Here, we introduce a Förster resonance energy transfer (FRET) channel at the hole‐transport layer (HTL)/perovskite interface by incorporating the ultraviolet absorber N‐(2‐ethoxyphenyl)‐N’‐(2‐ethylphenyl)oxamide (UV‐312). Under UV irradiation, UV‐312 adopts an enol‐resonant configuration that facilitates ultrafast FRET (∼20 ps) to the interface. This process promotes charge separation and suppresses UV‐induced Pb–I bond dissociation, thereby preserving the [PbI 6 ] 4– octahedral framework and enhancing UV‐stress resilience. Moreover, the rigid, extended conjugation of UV‐312 mitigates MeO‐2PACz aggregation, optimizing interfacial energy‐level alignment and minimizing stress inhomogeneity. Consequently, the champion device (aperture area: 0.09 cm 2 ) achieves a remarkable PCE of 27.05% with a high open‑circuit voltage of 1.186 V and a minimal non‐radiative voltage loss of only 61 mV. Impressively, the performance scales to 25.08% for a 1 cm 2 PSC and 23.00% for a 12.96 cm 2 mini‑module, accompanied by robust operational stability under continuous light, heat, and UV stress. This work redefines UV absorbers as active energy‐management units, offering a unified approach to simultaneously address efficiency and stability issues in perovskite photovoltaics.

Cavitand-MXene photocatalyst nanocomposite (Ce2S3/WO3@TiVC-CB) on the photodegradation of nevirapine

High‐Contrast Handedness Inversion in Circularly Polarized Organic Ultralong Phosphorescence Enabled by an Antagonistic Chirality‐Offset Helical Superstructure

ABSTRACT Dynamic and reversible control of circularly polarized ultralong room‐temperature phosphorescence (CP‐OURTP) is highly desirable for time‐gated chiroptical photonics. Yet, the simultaneous realization of handedness inversion and large dissymmetry factors remains challenging because inversion typically occurs near a net‐chirality cancellation point where the photonic bandgap (PBG) collapses. Here, we report a decoupled bilayer CP‐OURTP film that couples a room‐temperature phosphorescent polymer emitter with a photoresponsive chiral helical superstructure (CHS) engineered by an antagonistic chirality‐offset design. By pairing a high‐HTP chiral photoswitch with an oppositely handed static dopant, the net HTP reversibly crosses zero while remaining comparable in magnitude in the two photostationary states, thereby maintaining a robust PBG‐emission overlap on both sides of inversion. Consequently, the film delivers reversibly switchable g lum up to ±1.0 under alternating 365 and 530 nm irradiation, together with a phosphorescence quantum yield of 21.4%, an ultralong lifetime up to 388 ms, and stable operation over 50 switching cycles. The combined CP‐OURTP and selective circular‐polarization reflection enable high‐fidelity rewritable anti‐counterfeiting labels. This CHS‐engineering strategy provides a general route to CP‐OURTP materials with on‐demand chiroptical control for multi‐level information encryption and smart photonic devices.

Side Chains Override Crystallinity in n‐Type Organic Mixed Conductors

ABSTRACT In organic semiconductors, crystallinity is commonly associated with enhanced charge transport. For organic mixed ionic‐electronic conductors (OMIECs), materials at the core of bioelectronic devices, whether higher crystallinity consistently translates into improved performance remains unresolved. Here, we use thermal annealing to control the crystallinity of three electron‐transporting OMIECs bearing either branched or linear ethylene glycol side chains that are used to promote ion transport. Although annealing uniformly enhances crystallinity across all materials, it improves mixed charge transport only in polymers with linear side chains by doubling electronic charge mobility. Specifically, annealed films with branched side chains exhibit reduced mobility and low water uptake, coinciding with a pronounced bipolaron formation, which we uncovered using a combination of in‐operando physicochemical characterization methods. Thermal annealing is also used to sterilize these materials for interfacing with living cells, with the benefit of improved sensor performance. These results reveal that crystallinity can hinder mixed conductivity depending on side‐chain architecture, independent of the backbone chemistry. By challenging the prevailing assumption that crystallinity is universally beneficial for charge transport, this work establishes design rules for developing OMIECs that combine high performance with compatibility for fabrication and sterilization processes involving high temperatures, paving the way for reliable, scalable bioelectronic devices.

Effect of Atomic Layer Deposition of Ultra‐Thin Oxide on Reactivity and Durability of Perovskite Oxygen Electrodes

ABSTRACT Conductive perovskite oxides (ABO 3 ) are key oxygen electrode materials for energy conversion applications, but they suffer from irreversible performance degradation at elevated temperatures due to surface chemical instability. In this study, we investigate how the surface chemical environment and oxygen exchange kinetics of thin‐film La 0.6 Sr 0.4 CoO 3 are affected by the atomic layer deposition of binary oxides—specifically HfO 2 and Al 2 O 3 . We observe that both HfO 2 and Al 2 O 3 overcoats successfully maintain the rapid oxygen exchange rate on the electrode surface. Interestingly, however, their effects on the electrode surface chemistry differ significantly, as do the ideal coating thicknesses, as revealed by X‐ray photoelectron spectroscopy, secondary ion mass spectrometry, and transmission electron microscopy analyses. These findings suggest two distinct mechanisms for stabilizing the perovskite surface: the oxide overcoats (1) reduce oxygen vacancies that attract Sr ions to the surface and (2) act as a scavenger, consuming excess surface Sr, and suggest the design principle of a new strategy based on atomic layer deposition to improve perovskite surface durability.

Real-world overall survival after PD-1 failure in advanced cutaneous squamous cell carcinoma.

e21570 Background: Anti–PD-1 therapy Cemiplimab is standard first-line systemic treatment for advanced cutaneous squamous cell carcinoma (cSCC). However, optimal therapy following PD-1 failure is not well defined. We compared overall survival (OS) outcomes for patients who failed anti-PD-1 therapy and were subsequently treated with ipilimumab (anti-CTLA-4) versus cetuximab-based regimens (anti-EGFR ± chemotherapy) in a large real-world cohort. Methods: We conducted a retrospective cohort study using the Epic COSMOS database. The cohort included patients with advanced cSCC who progressed on first-line anti-PD-1 therapy. OS was estimated using Kaplan–Meier methods and compared between treatment groups using log-rank testing. Associations between baseline characteristics and survival were evaluated using univariable Cox proportional hazards models with false discovery rate (FDR) correction. Results: The cohort included 251 patients with a median age of 74.0 years; 73.7% were male, 93.0% were White, and 48.2% had a history of tobacco use. The median Charlson Comorbidity Index score was 10.0. The median OS (mOS) was 52 months (95% CI [37.3-NR]). In the univariate analysis of prognostic factors, a higher Charlson Comorbidity Index was the only factor significantly associated with worse survival (HR 1.09, 95% CI [1.04–1.15], FDR = 0.001). Age, sex, race, BMI, tobacco use, and residence were not significantly associated with outcomes. Out of 251 patients, 26 received ipilimumab, and 225 received cetuximab-based regimens, with 168 receiving cetuximab alone and 57 receiving it in combination with chemotherapy. There was no statistically significant difference in survival among the treatment groups (log-rank p = 0.54). The 48-month overall survival probabilities were 48.1% (95% CI 24.5–68.3%) for ipilimumab, 46.6% (95% CI 33.3–58.8%) for cetuximab monotherapy, and 40.4% (95% CI 20.0–54.0%) for cetuximab plus chemotherapy. Conclusions: In this real-world analysis of patients with advanced cSCC progressing on anti-PD-1 therapy, OS did not significantly differ between those treated with ipilimumab and those receiving cetuximab-based regimens. Comorbidity burden was the primary driver of survival outcome. Given the retrospective design and limited sample size of the ipilimumab cohort, prospective studies are warranted to better define optimal sequencing in this setting.

Proteomics-based phosphorylated AKT S473 and PI3K/AKT inhibitors in patients with hormone receptor–positive (HR+) metastatic breast cancer (MBC).

e13053 Background: Multiple PIK3CA/AKT/mTOR (PAM) pathway inhibitors have been FDA-approved for HR+ MBC with PIK3CA mutation or PTEN loss. There is a clinical unmet need for better characterization of biomarkers for responses and guidelines. We hypothesize that pretreatment phosphorylation sites of the PAM pathway may associate with clinical activity of PAM inhibitors. This retrospective analysis is designed to evaluate the clinical utility of a proteomics-based reverse phase protein microarrays (RPPA) assay in patients with HR+ PIK3CA mut+ MBC receiving PAM inhibitors. Methods: Through an IRB-approved protocol, a retrospective cohort of 107 patients with HR+ PIK3CA mut+ MBC receiving PIK3CA/AKT inhibitors was identified between January, 2019 and December 2025 at Cedars Sinai Medical Center. Of these, 20 had pretreatment from metastatic sites(n = 19) or primary breast tissue (n = 1) with FFPE tissue block available. The blocks underwent laser capture microdissection, lysis, and protein quantification via RPPA. Samples were stained for six AKT/mTOR pathway phosphoproteins and values converted to percentages based on an internal breast tumor reference population. Within this cohort, analyte values above the cohort median were defined as positive. The predictive value of AKT/mTOR protein phosphorylation for progression-free survival (PFS) or time to treatment discontinuation (TTD) following treatment with PI3K and AKT inhibitors (capivasertib, alpelisib, and inavolisib) was assessed in pre-treatment case samples using Wilcoxon rank-sum and Spearman’s Rho analysis. Results: Phosphoproteomic profiling identified significant clinical stratification, with AKT S473-positive samples (n = 9) demonstrating significantly longer mean PFS/TTD (10.3 months) compared to AKT S473-negative samples (n = 11, 5.25 months; Wilcoxon p < 0.05). Spearman’s Rho analysis confirmed a moderate correlation between AKT S473 levels and PFS/TTD (ρ = 0.38). Other AKT/mTOR pathway analytes did not show significant associations with clinical outcomes. Genomic analysis revealed PI3K/AKT/PTEN mutations in 95% (19/20) of samples; 18 with PIK3CA mut, and 1 with AKT mut. There is no clear association between genomic mutation vs PFS; no association between AKT/mTOR pathway analytes and the genomic alterations, likely due to limited sample size. Conclusions: In this pilot study, AKT S473 positivity emerged as a potential predictive biomarker in PI3K/AKT inhibitor-treated breast cancer, where PI3K/AKT/PTEN genomic mutations were ubiquitous. This suggests that the quantification of phosphorylated AKT may be a better predictor of response to treatment with PI3K or AKT kinase inhibitors than genomic alteration status. Further validation in a larger cohort is warranted to confirm the clinical utility of this approach.

First-line datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option: Additional efficacy endpoints from the TROPION-Breast02 study.

1002 Background: In the primary analysis of the phase 3 TROPION-Breast02 study (NCT05374512), first-line Dato-DXd demonstrated statistically significant and clinically meaningful improvements in overall survival (OS; hazard ratio [HR]: 0.79 [95% confidence interval [CI]: 0.64–0.98]; p = 0.0291) and progression-free survival (PFS; HR: 0.57 [95% CI: 0.47–0.69]; p < 0.0001) compared with investigator’s choice of chemotherapy (ICC) in patients with locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. Both median OS and PFS by blinded independent central review (BICR) were ≥5 months longer with Dato-DXd compared with ICC. Moreover, with Dato-DXd vs ICC, the confirmed objective response rate was more than double and median duration of response was > 5 months longer. The Dato-DXd safety profile was manageable and generally consistent with the known profile. Here we report additional efficacy endpoints. Methods: Adult patients with previously untreated locally recurrent inoperable or metastatic TNBC, for whom immunotherapy was not an option, were randomized 1:1 to Dato-DXd (6 mg/kg IV every 3 weeks) or ICC ([nab]-paclitaxel/capecitabine/eribulin mesylate/carboplatin). Dual primary endpoints were OS and PFS by BICR per RECIST 1.1; secondary endpoints included time to second progression or death (PFS2), time to first subsequent therapy or death (TFST), and time to second subsequent therapy or death (TSST). The planned sample size was approximately 600 randomized patients. A stratified log-rank test was used to analyze PFS2, TFST, and TSST. HRs and 95% CIs were estimated from a stratified Cox proportional hazards model. Results: A total of 644 patients were randomized (Dato-DXd: 323; ICC: 321). At data cutoff (25 Aug 2025), median study follow-up was 27.5 months and 53 (8.4%) patients remained on treatment (Dato-DXd: 45 [14.1%]; ICC: 8 [2.6%]). PFS2 was longer with Dato-DXd vs ICC: median 15.6 vs 11.8 months (HR: 0.61 [95% CI: 0.50‒0.74]). Both TFST and TSST were prolonged in the Dato-DXd vs ICC arm: median TFST was 10.9 vs 5.6 months with Dato-DXd vs ICC (HR: 0.49 [95% CI: 0.41‒0.59]) and median TSST was 16.7 vs 12.6 months (HR: 0.67 [95% CI: 0.55‒0.81]). Conclusions: In TROPION-Breast02, improvements in the secondary endpoints of PFS2, TFST, and TSST were observed for patients receiving Dato-DXd compared with ICC, consistent with the dual primary endpoints of OS and PFS by BICR. Alongside the manageable safety profile for Dato-DXd, these data further support Dato-DXd as the new first-line standard of care in this setting. Clinical trial information: NCT05374512 .

Development of a computational histology artificial intelligence (CHAI)–powered predictive biomarker for first-line chemotherapy intensification in metastatic colorectal cancer (mCRC) and validation in prospective randomized phase III trials (RCT).

3513 Background: In unresectable mCRC, meta-analysis of RCTs suggests triplet therapy consisting of fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI) + bevacizumab (bev) may improve survival outcomes over doublet regimens of fluorouracil with irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) + bev, at the expense of increased toxicity. Adoption of triplet therapy remains low. A histology-based biomarker to predict outcomes in mCRC treated with triplet vs doublet regimens could optimize treatment selection. We aimed to use the previously described CHAI platform to develop and validate a histology-based predictive biomarker for doublet vs triplet therapy in mCRC with participant-level data from 3 RCTs. Methods: Development used diagnostic H&E-stained whole slide images (WSI) from participants with mCRC treated with first-line (1L) chemotherapy enrolled in the MRC FOCUS RCT. WSIs were analyzed using the CHAI assay and trained towards clinical outcomes as a function of chemotherapy escalation. Weighting of histologic features was optimized for association with progression-free (PFS) & overall survival (OS) to construct a signature that was combined with tumor sidedness to create the mCRCpred biomarker. A cutpoint was selected to optimize treatment effect stratification, assigning each case a binary label. The locked biomarker was evaluated on the independent validation cohort of WSIs from the TRIBE + TRIBE2 RCTs. The association of the biomarker-treatment interaction with PFS & OS was evaluated with multivariable (MVA) Cox models & Likelihood Ratio tests. Results: The development cohort included 294 cases from MRC FOCUS. The independent validation cohort (n = 386) comprised cases from TRIBE (n = 159) and TRIBE2 (n = 227). 193 (50%) had 1L triplet+bev and 193 (50%) doublet+bev. Biomarker (+) (indicative of triplet benefit) disease treated with triplet+bev had superior 3-year PFS (17% vs 7%, HR = 0.51 [0.37, 0.70], p < 0.001) and OS (43% vs 22%, HR = 0.51 [0.35, 0.73], p < 0.001) versus doublet+bev. Biomarker (-) cases treated with triplet+bev vs doublet+bev had no significant differences in PFS (5 vs 15%, HR = 1.30 [0.96, 1.74], p = 0.09) or OS (31 vs 40%, HR = 1.35 [0.94, 1.92], p = 0.1). In MVA including cohort, age, ECOG, number of metastatic sites, and timing of metastasis (metachronous/synchronous), the biomarker-treatment interaction was significant (p < 0.001) indicating a predictive association between the biomarker and treatment regimen. Conclusions: The CHAI mCRCpred histology-based biomarker predicted differential benefit of chemotherapy escalation (doublet-bev vs triplet-bev) as 1L therapy in mCRC, with independent validation post-hoc in two RCTs (Simons Level of Evidence IB). This biomarker may guide optimal treatment selection for 1L mCRC. Clinical trial information: ISRCTN79877428 (FOCUS); NCT00719797 (TRIBE); NCT02339116 (TRIBE2).

Changes in immunocompetent blood cells in patients with recurrent ovarian cancer depending on platinum sensitivity.

e17550 Background: Despite surgery and adjuvant chemotherapy, up to 80% of patients with ovarian cancer (OC) experience recurrence. Treatment choice depends on the platinum-free interval. Assessment of the immune system may identify novel markers of treatment response for therapy personalization and outcome improvement. This study aimed to evaluate blood immune cell subpopulations according to platinum sensitivity in recurrent OC patients. Methods: The study included patients with serous adenocarcinoma (mean age 57.53 ± 2 years). The main group (n=30) comprised patients with recurrent OC, subdivided into platinum-sensitive (n=15) and platinum-resistant relapse (n=15). A control group (n=30) was presented with patients in remission. Peripheral blood samples were collected before treatment and analyzed by flow cytometry for major and minor lymphocyte populations. Statistical analysis was performed using STATISTICA 13.3 software. Results: In the platinum-sensitive subgroup total lymphocyte count increased by 43%, accompanied by a 142% increase in NKT cells and a 34% decrease in NK cells comparing to control group (p<0.05). A 20% increase in CD4⁺CD8⁺ cells was noted. Myeloid populations also increased: CD33⁺ (33%), CD14⁺CD15⁺CD11b⁺ (86%), CD14⁺CD11b⁺CD33⁺ (200%), and CD14⁺CD15⁺CD33⁺ (233%) (p<0.05). In the platinum-resistant subgroup, total lymphocytes increased by 33%, NKT cells by 89% (p<0.05), and CD4⁺CD8⁺ cells by 50%. Myeloid markers CD14⁺CD11b⁺CD33⁺ and CD14⁺CD15⁺CD33⁺ increased by 100% and 200%, respectively (p<0.05). Conclusions: There are significant differences in peripheral blood immune cell profiles between platinum-sensitive and platinum-resistant recurrent ovarian cancer. These distinct immune signatures may serve as potential markers for disease stratification and treatment personalization.