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Evaluating the safety of immune checkpoint inhibitors prior to liver transplant.

614 Background: Liver transplantation (LT) offers a 5-year survival exceeding 70% for selected patients with hepatocellular carcinoma (HCC). Immune checkpoint inhibitors (ICIs) may be used to downstage or bridge to transplantation. This study aims to evaluate the safety of ICIs prior to LT. Methods: Multicenter retrospective study, involving 9 centers, included adults who received ICIs and, subsequent LT, between 2019 and 2023. The ICI cohort was matched by age, sex, liver diseases and transplant date (1:3) with a similar cohort of HCC transplanted patients that did not receive ICIs. Results: The ICI cohort included 45 patients (Table part 1). The most common underlying liver diseases were viral. 15.5% of patients had macrovascular invasion and, 62.2% multifocal disease. The most commonly used ICI was nivolumab (75.6%), followed by atezolizumab-bevacizumab (17.8%). The median follow up was 32.5 months (17.4 - 47.6). The median ICI duration was 147 days (129.5-276.5), with a median interval of 58 days (22–193) between the last ICI dose and LT. There were 8 (17.8%) cases of graft rejection, 2 steroid-resistant leading to 1 graft failure. There were 4 (8%) HCC recurrences. During follow-up there were 6 deaths, 2 related to HCC recurrence and 4 non liver related. When compared with 135 non-ICI cohort patients, there were no differences within the groups (Table part 2). Importantly, we found no significant differences in crude rejection rates (p=0.5). Conclusions: Our study suggest that ICI treatment prior to LT is safe. ICI rejection primarily occurs in the acute post-transplant period (within 3 months), with a low risk of death due to graft failure. Further clinical trials are needed. Part 1: ICI cohort descriptive analysis. N (%); Median (IQR); Part 2: Comparison between cohorts. N (%); Mean (SD). (part 1) ICI-cohort n=45 General data Male 38 (84.4) Age 61.2 (7.6) Etiology of liver diseases Hepatitis C 17 (37.8)Hepatitis B 6 (13.3)MASLD 6 (13.3)Viral +Alcohol 5 (11.1)Alcohol 3 (6.7)Autoimmune 3 (6.7)Other 3 (6.7)Combined viral 2 (4.4) Largest tumor (mm) 39 (22) Macrovascular invasion 7 (15.5) Multifocal 28 (62.2) Locoregional therapy 36 (80.0) Number of locoregional therapies 2 (2) Immunotherapy Nivolumab 34 (75.6) Atezolizumab/bevacizumab 8 (17.8) Pembrolizumab 1 (2.2) Nivolumab+pembrolizumab 1 (2.2) PD1 inhibitor clinical trial 1 (2.2) Days of ICI treatment 147 (203) Radiological tumor response ICI No 17 (37.8) Transplant Deceased donor 43 (95.6) Washout period (days) 58 (171) Induction therapy (anti-thymoglobulin) 8 (17.8) Outcomes Rejection Biopsy proven 8 (17.8) 8 (100) Time to rejection (days) 43 (102) Graft failure Rejection 2 (4.4)1 (2.2) HCC recurrence 4 (8) Deaths 6 (13.3) Follow up Since transplant (months) 32.5 (30.2) (part 2) ICI-cohort (n=45) Non-ICI cohort (n= 135) P Post transplant rejection rate 8 (17.8) 32 (23.7) 0.53 Time to rejection (days) 180.1 (SD 218) 62.2 (SD 62.8) 0.25 Overall deaths 6 (13.3) 10 (7.4) 0.36

Non‐Interleaved Shared‐Aperture Full‐Stokes Metalens via Prior‐Knowledge‐Driven Inverse Design (Adv. Mater. 8/2025)

Formation Dynamics of Thermally Stable 1D/3D Perovskite Interfaces for High‐Performance Photovoltaics

Abstract Direct understanding of the formation and crystallization of low‐dimensional (LD) perovskites with varying dimensionalities employing the same bulky cations can offer insights into LD perovskites and their heterostructures with 3D perovskites. In this study, the secondary amine cation of N ‐methyl‐1‐(naphthalen‐1‐yl)methylammonium (M‐NMA + ) and the formation dynamics of its corresponding LD perovskite are investigated. The intermolecular π–π stacking of M‐NMA + and their connection with inorganic PbI 6 octahedrons within the product structures control the formation of LD perovskite. In an N,N‐ dimethylformamide (DMF) precursor solution, both 1D and 2D products can be obtained. Interestingly, due to the strong interaction between M‐NMA + and the DMF solvent, compared to the 1D phase, the formation of 2D perovskites is uniquely dependent on heterogeneous nucleation. Nevertheless, post‐treatment of 3D perovskite films with an isopropanol solution of M‐NMAI leads to the exclusive formation of thermally stable 1D phases on the surface. The resulting 1D/3D heterostructure facilitates perovskite solar cells (PSCs) to not only achieve a record efficiency of 25.51% through 1D perovskite passivation but also significantly enhance the thermal stability of unencapsulated devices at 85 °C. This study deepens the understanding of the formation dynamics of LD perovskites and offers an efficient strategy for fabricating stable and high‐performance PSCs.

Prognostic implication of body composition changes in patients with borderline resectable/locally advanced pancreatic adenocarcinoma (PDAC) treated with mFOLFIRINOX.

783 Background: Although cachexia is a known prognostic factor in patients with advanced cancer, individual body composition changes during chemotherapy and their association with survival in PDAC warrant further investigation. We aimed to analyze the prognostic implication of comprehensive body composition, including areas and attenuation of muscle mass, body fat area and its distribution, and body mass index (BMI) during mFOLFIRINOX in patients with PDAC. Methods: Patients with borderline resectable or locally advanced PDAC, who were not able to undergo curative surgery and received first-line mFOLFIRINOX between January 2017 and December 2020 from Asan Medical Center, Seoul, Korea, were included in this retrospective study if they had paired CT scans of the abdomen at baseline and after 12 weeks of mFOLFIRINOX. Body composition was measured using artificial intelligence software (AID-UTM, iAID Inc.) from the CT images, and their association with overall survival (OS) were analyzed. Results: A total of 377 patients were included. Median age was 63 (range, 56–69) and 214 patients (56.8%) were males and 163 patients (43.2%) were females. During the first 12 weeks, significant changes in the body composition occurred as follows (median changes and interquartile range): skeletal muscle area, -5.8% [-11.1%–0.6%]; normal attenuation muscle area/total attenuation muscle area, -2.8% [-8.7%–3.2%]; visceral fat area (VFA), -6.1% [-23.7%–18.6%]; skeletal fat area (SFA), -12.2% [-27.8%–77.1%]; and BMI, -2.2% [-6.8%–1.5%]. Furthermore, changes in the VFA and BMI was associated with tumor response (Kruskal-Wallis test, p = 0.012 for VFA; p = 0.054 for BMI). There was no significant relationship between body composition abnormalities including sarcopenia, myosteatosis, or obesity at baseline and OS. However, patients who experienced the greatest decrease in SFA and BMI after 12 weeks of mFOLFIRINOX had poorer OS (tertile 1 [greatest decrease] vs 3 [smallest decrease]: HR 0.67 [95% CI, 0.52–0.87] for SFA, p = 0.003; 0.68 [95% CI, 0.49–0.83] for BMI, p = 0.001). Conclusions: In patients with borderline resectable/locally advanced PDAC, body composition significantly changes during the first 12 weeks. Decrease in the body fat and BMI from baseline were associated with poorer tumor response and OS.

First-line iparomlimab and tuvonralimab (QL1706) or iparomlimab (QL1604) + bevacizumab (BEV) for unresectable hepatocellular carcinoma (HCC): Updated results from the phase Ib/II DUBHE-H-106 study.

579 Background: Novel treatment options for unresectable HCC are needed. Iparomlimab and tuvonralimab are anti-PD-1 and anti-CTLA-4 antibodies, respectively. The DUBHE-H-106 study aims to assess safety and efficacy of first-line QL1706 or QL1604 + BEV for HCC. Preliminary data have been reported on 2023 ASCO Annual Meeting. Here, we report updated results. Methods: This study consists of three cohorts. Systemic therapy-naive adult patients (pts) with HCC, ≥ one measurable untreated lesion per RECIST v1.1, BCLC stage B–C, Child-Pugh score ≤ 7, not amenable to or progression after locoregional therapy, ECOG performance status of 0–1 were eligible. In Cohort A, six pts received QL1706 5 mg/kg + BEV 15 mg/kg Q3W. If ≤ two pts had dose-limiting toxicities (DLT), another six pts would be enrolled. If ≤ three of twelve pts had DLT, the safe dose of BEV would be determined, and eight more pts would be enrolled. Otherwise, enrollment of another dose group (QL1706 5 mg/kg + BEV 7.5 mg/kg Q3W) would initiate, using the same procedure. If number of DLT exceeded the criteria, further dose reduction of BEV or study termination would be discussed. Then 40–60 pts were randomized 1:1 to Cohort A or B. In Cohort B, pts received QL1604 200 mg + BEV (safe dose) Q3W. Enrollment of Cohort C would initiate according to the preliminary results of Cohort A and B. Pts received QL1706 7.5 mg/kg + BEV (safe dose) Q3W, using the same procedure in Cohort A. If ≤ three of twelve pts had DLT, 8–28 more pts would be enrolled. Results: Between Jun 2021 and Dec 2023, Cohort A, B, and C included 50, 26, and 40 pts, respectively. Baseline data were balanced in each cohort. All pts were in the safety set. No DLT was reported. Incidences of adverse events (AE) were similar in three cohorts. Efficacy evaluable set included 47, 26, and 37 pts in three cohorts. Numerically, QL1706 + BEV showed better efficacy compared to QL1604 + BEV, and higher response and 12-month progression-free survival (PFS) rates were found in Cohort C vs Cohort A. Detailed results were shown in Table. Conclusions: First-line QL1706 or QL1604 + BEV showed acceptable toxicities and promising efficacy for unresectable HCC. QL1706 7.5 mg/kg + BEV 15 mg/kg Q3W may have better anti-tumor activity and were recommended for trials in future. Clinical trial information: NCT05603039 . Endpoints Cohort A Cohort B Cohort C Treatment-related AE (TRAE) 43 (86%) 25 (96%) 37 (92%) Grade ≥ 3 TRAE 24 (48%) 14 (54%) 16 (40%) Serious TRAE 11 (22%) 9 (35%) 10 (25%) Immune-related AE 27 (54%) 9 (35%) 22 (55%) TRAE leading to dose interruption 23 (46%) 16 (62%) 16 (40%) Objective response, n (%; 95% CI) 18 (38%; 25%–54%) 6 (23%; 9%–44%) 16 (43%; 27%–61%) Disease control, n (%; 95% CI) 35 (74%; 60%–86%) 18 (69%; 48%–86%) 30 (81%; 65%–92%) Median PFS (95% CI), months 7.0 (3.1–9.6) 5.4 (2.4–11.0) 7.0 (4.2–not evaluable) 12-month PFS rate (95% CI) 26.8 (14.7–40.4) 24.4 (9.9–42.1) 40.9 (24.3–56.9)

Final analysis of the randomized phase 2 part of the ASPEN-06 study: A phase 2/3 study of evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, in patients with HER2-overexpressing gastric/gastroesophageal cancer (GC).

332 Background: Evorpacept (Evo) is a high affinity, CD47-blocker with an inactive Fc region designed to safely magnify anticancer antibody dependent cellular phagocytosis. Evorpacept is being evaluated across cancers, in combination with anticancer antibodies and checkpoint inhibitors. Methods: The ASPEN-06 randomized phase 2 trial evaluates Evo in combination with standard trastuzumab (T), ramucirumab (R) and paclitaxel (P) for the treatment of patients with HER2+ GC. Patients with 2 nd or 3 rd line HER2+ advanced or metastatic GC that has progressed on or after prior anti-HER2 therapy were randomized to Evo (30 mg/kg Q2W) plus TRP or TRP. HER2 status was determined in the most recent GC tissue sample. Primary study objectives were to compare confirmed ORR of Evo-TRP to an assumed ORR of RP (=30%) with one-sided alpha error of 0.025 and to identify a clinically meaningful contribution of Evo to TRP in ORR (delta>10%). Results: Among the entire randomized population (N=127) the ORR was 40.3% (Evo-TRP) and 26.6% (TRP), respectively. The difference between Evo-TRP's ORR compared to historical RP's ORR was not statistically significant (p=0.095), but Evo-TRP's ORR demonstrated a meaningful delta of 13.7% over TRP's ORR (p=0.028 in an exploratory analysis). Median DOR for Evo-TRP and TRP was 15.7 and 7.6 months, respectively. In a prespecified population with HER2+ disease in fresh tumor tissues after prior anti-HER2 treatment (N=48), Evo-TRP's ORR (54.8%) compared favorably to historical RP's ORR (p=0.030) with a delta of 31.7% over TRP's ORR of 23.1% (p=0.004 in an exploratory analysis). Evo-TRP was well tolerated with a safety profile consistent with prior experience. Updated results including PFS will be presented at the meeting. Conclusions: The addition of Evo to TRP showed promising activities in HER2+ GC. The magnitude of response was greatest in tumors identified as HER2+ using fresh biopsies emphasizing the importance of biopsies post anti HER2 therapy. Consistent with Evo’s mechanism of enhancing antibody dependent phagocytosis, these data support its ongoing investigation as an adjunct to anti-HER2 gastric cancer therapy. Clinical trial information: NCT05002127 .

Tailorable Fluorescent Perovskite Quantum Dots for Multiform Manufacturing via Two‐Step Thiol‐Ene Click Chemistry (Adv. Mater. 5/2025)

Molecular Ferroelectrics for Highly Sensitive Detection Toward Low‐Frequency Sound Recognition

Abstract Human hearing cannot sensitively detect sounds below 100 Hz, which can affect the physical well‐being and lead to dizziness, headaches, and nausea. Piezoelectric acoustic sensors still lack sensitivity to low‐frequency sounds owing to the low piezoelectric coefficient or high elastic modulus of materials. The low elastic modulus and substantial piezoelectric coefficient of molecular ferroelectric materials make them excellent candidates for acoustic sensors. In this study, the molecular ferroelectric, [(CH 3 ) 3 NCH 2 Cl]CdCl 3 , is used as a piezoelectric active layer in the construction of a piezoelectric acoustic sensor for low‐frequency sound detection. The sensor exhibits high sensitivity (47.43 mV Pa −1 cm −2 ) at 87 Hz, with an excellent level of frequency resolution (up to 0.1 Hz). This facilitates the accurate discrimination and detection of low‐frequency sounds, which is suitable for noise detection applications. The sensor differentiates between various musical instruments and heartbeats, and recognizes audio signals. This study highlights the potential of molecular ferroelectric materials in piezoelectric acoustic device applications, including noise detection, health monitoring, and human‐computer interactions.

Adjuvant therapy with somatostatin analogs for recurrent gastric neuroendocrine tumors type 1.

665 Background: Neuroendocrine gastric tumors (gNETs) type 1 are associated with chronic autoimmune atrophic gastritis, hypergastrinemia and usually have multifocal lesions and high frequency of recurrence (up to 70% for 2 years). Somatostatin analogs (SA) showed promising data in neoadjuvant setting with 84% of complete responses in a small retrospective trial. The aim of this study was to evaluate the efficacy of adjuvant treatment with SA for recurrent gNETs type 1. Methods: This retrospective, single-center study included patients (pts) with recurrent gNETs who received adjuvant treatment with SA. Recruitment of pts was carried out from 2012 to February 2024. Results: The study included 35 pts, 33 females and 2 males. Endoscopic mucosal resection (EMR) was performed in 34 cases (97.1%), gastric resection in 1 (2.9%). The median of previous EMR was 2 (1-6) procedures. Most of the pts have multifocal lesions – 28 (80%), the median of lesions is 5. The median tumor size – 6 mm, tumor size >10 mm was observed in 2 cases (5.7%), one of them had N+. The median of ki67 was 3,5% (1-10%), grade 1 (G) - 14 (40%) and G2 - 21 (60%). All pts received adjuvant therapy with SA, 33 (94.3%)long-active releasing octreotide30 mg and 2 (5.7%) lanreotide 120 mg every 4 weeks. The time of SA therapy was <12 months in 23 cases (65.7%) and ≥12 months in 12 (34.3%). The median of follow-up was 30.5 months. The median disease-free survival (DFS) was not reached (95% CI, 67-NR). We compared median DFS after previous EMR (DFS1) without adjuvant SA and DFS after EMR with adjuvant SA (DFS2). The DFS2 was significantly higher – median of DFS1 was 8.8 months (95% CI, 2.7-14.9) not reached (95% CI, 67-NR, p<0.01) . Adjuvant treatment with SA ≥12 months was associated with improved DFS compared to <12 months – not reached (95% CI, 58.1-NR) versus 61 months (95% CI, 26.2-96.2, p=0.05). Adjuvant SA reduced gastrin levels after a year of therapy by ≥50% from baseline in 13 cases (37.1%). Conclusions: Adjuvant treatment with SA significantly improved DFS and should be considered for recurrent and multifocal gNETs type 1. Duration of therapy ≥12 months was significantly associated with improvement in DFS compared with shorter duration of therapy.

A phase 1b dose escalation trial of gemcitabine and nab-paclitaxel in combination with lixumistat in patients with advanced pancreatic cancer.

743 Background: Despite recent advances, there are limited effective therapeutic options for pancreatic ductal adenocarcinoma (PDAC). Conventional chemotherapy can be difficult to tolerate and offers modest survival benefits. Lixumistat is a small molecule biguanide that inhibits the first and rate-limiting step of the oxidative phosphorylation pathway, which is critical to the survival of PDAC tumor cells. A first-in-human dose escalation trial of Lixumistat in solid tumors demonstrated a favorable safety profile and a recommended phase 2 dose (RP2D) of 800 mg per day (QD) (1). Methods: A single center Phase 1b study is currently enrolling patients with treatment-naïve metastatic PDAC to evaluate the safety and tolerability of Lixumistat when combined with standard-of-care gemcitabine (Gem) plus nab- paclitaxel (NP) (NCT05497778). The initial escalation cohort received oral Lixumistat at 400 mg QD; the subsequent escalation cohort received oral Lixumistat at 800 mg QD. All patients also receive fixed doses of intravenous (IV) NP (125 mg/m 2 ) and IV Gem (1000 mg/m 2 ) on Days 1, 8, and 15 (28 day cycle). Here we report the preliminary results from the escalation phase of the trial. Results: Thirteen patients have been treated: 7 at 400 mg and 6 at 800 mg. There were no grade 4-5 toxicities. Two patients experienced a DLT at the 800 mg dose (grade 3 diarrhea and grade 3 fatigue); no DLTs were observed at the 400 mg dose. The most common Lixumistat related toxicities were Grade 1/2 nausea/vomiting (controlled with anti-emetics), skin rash, fatigue, and diarrhea. Grade 1-3 thrombocytopenia, neutropenia, and peripheral sensory neuropathy events were no more than expected with this combination and managed with Gem/NP dose reduction, omission of day 8, or therapy hold until resolved to Grade 1. Based on toxicities observed at 800 mg, 400 mg is the RP2D. Among 6 response-evaluable patients treated at the RP2D, 2 achieved an objective partial response (ORR = 33%, 95% CI: 4.3%-77.3%); 4 patients had stable disease with tumor shrinkage observed in 3 of these patients (12%, 22% and 23% reduction); and the DCR was 100% (95% CI: 54.1%-100%). Notably, a patient from the 800 mg cohort who was dose reduced to 400 mg after DLT achieved a complete response in their target lesions. Current median follow-up time is 13.2 months, and 2 patients have died. Estimated median PFS is 12.9 months (95% CI: 3.65, NA) and estimated median OS is 18 months (95% CI: 6.42, NA). Four patients remain on active treatment at the time of analysis. Conclusions: When combined with Gem and NP; a dose of 400 mg of Lixumistat QD was demonstrated to be safe, tolerable and identified as the RP2D. This trial is currently enrolling patients at the RP2D in the expansion cohort. Updated data on safety and efficacy will be presented at the meeting. 1. Janku 2022. Clinical trial information: NCT05497778 .

Exploring the link between liver cirrhosis and liver metastasis in colorectal cancer.

301 Background: Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer mortality in the world. Although it is now associated with improved outcomes due to advancements in treatment modalities, CRC continues to be the most common source of liver metastasis. Previous studies have shown cirrhotic livers to be at reduced risk of metastatic disease. Our study aims to investigate the association between colorectal cancer and liver metastasis in the presence of concomitant liver cirrhosis. Methods: The National Inpatient Sample (NIS) was queried to identify all hospitalizations with colorectal cancer utilizing ICD-10 codes C18.x, C19.x, and C20.x from 2016 to 2020 and were further classified based on the presence or absence of cirrhosis. Demographic and clinical data were analyzed using chi-squared tests, independent sample t-tests, and binary logistic regression (adjusted for age, gender, and Charlson comorbidity index or CCI). The primary outcome studied was liver metastasis. Secondary outcomes were hepatic encephalopathy, portal hypertension, and spontaneous bacterial peritonitis. Statistical significance is indicated by a p-value less than 0.05. Results: A total of 255,599 hospitalizations with colorectal cancer were identified. Out of these, 5,370 (2.1%) had liver cirrhosis and 250,229 (97.9%) did not. Hospitalizations with CRC and concomitant cirrhosis had higher comorbidities as per the Charlson Comorbidity Index (10.5 vs 8.1, p-value<0.001) and higher mortality rates (8.5% vs 4.2%, p-value<0.001). Higher rates of liver metastasis (26.5 vs 23.4, p <0.001) and portal hypertension (26.1% vs 0.3%, p<0.001) were observed in the cirrhosis subgroup. This subgroup also has a significantly higher risk of SBP (2.8% vs 0.2%, p <0.001). Conclusions: This is a large retrospective study analyzing the impact of cirrhosis on liver metastasis in patients with colorectal cancer. Patients with concomitant cirrhosis consistently have increased liver metastasis and worse outcomes. The results of this study imply that diligent CRC screening is of utmost importance in patients with cirrhosis. Patients with CRC and coexisting cirrhosis would benefit from routine surveillance such as carcinoembryonic antigen (CEA) screening or CT scans to allow early detection of liver metastases which could potentially improve outcomes. Colorectal Cancer Patients No Cirrhosis (N=250,229) Cirrhosis (N=5,370) p-value Age (in years) 65.79 ± 13.8 65.04 ± 10.9 <.001 Sex (Female) 47.3% 36.8% <.001 Charlson Comorbidity Index 8.1 ± 3.6 10.5 ± 3.7 <.001 Mortality 4.2% 8.5% <.001 Length of Stay 6.6 ± 7.2 7.4 ± 7.2 <.001 Liver Metastasis 23.4% 26.5% <.001 Hepatic Encephalopathy 0.0% 0.2% <.001 Portal hypertension 0.3% 26.1% <.001 Spontaneous Bacterial Peritonitis (SBP) 0.2% 2.8% <.001

Precise Cell Type Electrical Stimulation Therapy Via Force‐electric Hydrogel Microspheres for Cartilage Healing (Adv. Mater. 7/2025)

Extending Exciton Diffusion Length via an Organic‐Metal Platinum Complex Additive for High‐Performance Thick‐Film Organic Solar Cells

AbstractThe long exciton diffusion length (LD) plays an important role in promoting exciton dissociation, suppressing charge recombination, and improving the charge transport process, thereby improving the performance of organic solar cells (OSCs), especially in thick‐film OSCs. However, the limited LD hinders further improvement in device performance as the film thickness increases. Here, an organic‐metal platinum complex, namely TTz‐Pt, is synthesized and served as a solid additive into the D18‐Cl:L8‐BO system. The addition of TTz‐Pt enhanced the crystallinity of blends, reduced energy disorder, and trap density, and decreased non‐radiative recombination and exciton binding energy, which is conducive to prolonging the LD in the TTz‐Pt‐treated film, thereby facilitating the exciton dissociation and charge transport process along with inhibiting the charge recombination. Consequently, the TTz‐Pt‐treated D18:L8‐BO:IDIC device (100 nm) exhibits a champion power conversion efficiency (PCE) of 20.12% (certified as 19.54%), one of the highest PCEs reported for OSCs to date. Remarkably, a record‐breaking PCE of 18.84% is yielded for the active layer thickness of 300 nm. Furthermore, the TTz‐Pt exhibits superior universality in improving the performance of OSCs. This work provides a simple and universal approach to extending LD by introducing an organic‐metal platinum complex as a solid additive to achieve highly efficient thick‐film OSCs.

Transarterial infusion chemotherapy and embolization (TAICE) as a pre-operative therapy for patients with locally advanced gastric cancer (LAGC): A prospective, single-arm, pilot study.

436 Background: Interventional therapy is a local intensive therapy for tumor control, often utilized in palliative treatment for solid organ tumors. Yet, its application in tumors of hollow viscera still lacks evidence. Our previous retrospective study revealed transarterial infusion chemotherapy and embolization (TAICE) not only effectively managed tumor-related hemorrhage but also exhibited a notable anti-tumor efficacy in gastric cancer. This prospective study aims to further explore the feasibility and safety of TAICE as a pre-operative therapy for locally advanced gastric cancer (LAGC). Methods: Patients diagnosed with locally advanced adenocarcinoma of stomach and gastrointestinal junction (GEJ) with no distant metastasis (cT3-4N+M0) were enrolled. They were given 4 cycles of pre-operative treatments: 2 cycles of TAICE-SOX (Oxaliplatin [85mg/m 2 transarterial infusion on Day 1] and S-1 [40/50/60mg po bid on Day 1-14]) and 2 cycles of SOX (Oxaliplatin [130mg/m 2 IV on Day 1] and S-1 [same as above]), alternately. Then, they received D2 radical gastrectomy, and 4 cycles of SOX post-operatively. In brief, the TAICE procedure was summarized into 4 steps: 1) Celiac arteriography, 2) Super-selection of tumor feeding artery (TFA), 3) Infusion chemotherapy and embolization of TFA, 4) Celiac re-arteriography to ensure the success of embolization. The primary endpoint was pathological complete response (pCR) rate. Other endpoints included major pathological response (MPR) rate, overall survival (OS), progression-free survival (PFS), treatment-related adverse events (TRAEs). Results: Between December 2020 and June 2023, twenty patients were enrolled and all of them received TAICE. Among them, 18 (90.0%) patients received 2 cycles of TAICE. The pCR and MPR rate were 55.0% and 70.0%, respectively. The 1-year and 3-year OS rate were 100.0% and 82.6%. The 1-year and 3-year PFS rate were 90.0% and 67.3%. There was no difference in OS between the groups of high and low tumor residual rate with the threshold of 50%. Patients achieving low tumor residual rate had significantly longer PFS (NR vs. 12.17 months, p=0.018) than those with high rate after TAICE. Moreover, we divided TFA into two subtypes: dispersive and branching, depending on the vascular pattern presented in the angiography at the first cycle TAICE. Patients with dispersive TFA had higher risk of recurrence after TAICE (NR vs. 15.17 months, p=0.0264). All patients had TRAEs (vomiting, nausea, abdominal pain and fever) of grade 1 or 2 after the first cycle of TAICE. Only one patient experienced nausea of grade 3 after the second cycle of TAICE. The most common TRAEs were vomiting and nausea. Conclusions: TAICE is a promising pre-operative therapy for patients with LAGC for it displaying the satisfactory oncological effectiveness and safety profile. Clinical trial information: NCT05396326 .

Niraparib in patients with <i>BRCA</i> -mutated unresectable or recurrent biliary tract, pancreatic and other gastrointestinal cancers: An investigator-initiated phase 2 trial (NIR-B trial).

589 Background: It has been reported that there are BRCA1/2 -mutated patients in biliary tract, pancreatic, and other gastrointestinal cancers. Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor, and PARP inhibitors exert their cytotoxicity against cancer cells in the context of homologous recombination deficiency, such as BRCA mutations. Methods: Main eligibility criteria are unresectable, advanced or recurrent biliary tract cancers (BTC; cohort A), pancreatic cancers (PC; cohort B), and other gastrointestinal cancers (cohort C) with BRCA1/2 gene mutations identified by germline test or genomic profiling test with either circulating tumor DNA (ctDNA) or tumor tissue, refractory or intolerant to previous treatments, and adequate organ function. Patients with body weight of 77 kg or more and a platelet count of 150,000 /µL or more receive 300 mg of niraparib, and less than 77 kg or having a platelet count less than 150,000 /µL received 200 mg of niraparib, orally once daily, until disease progression or intolerable adverse events occurred. Primary endpoint was the investigator-assessed objective response rate (ORR) in each cohort with a threshold response rate of 10% and an expected response rate of 35%. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Furthermore, pre-treatment ctDNA was collected and analyzed by Guardant360. Results: A total of 62 pts, 26 in cohort A, 26 in cohort B, and 10 in cohort C were enrolled between March 2021 and April 2023. Because one patient in cohort C did not receive protocol treatment, 61 pts were identified for primary efficacy and safety analysis. Median number of prior regimens was 1/2/2 (range, 1–2/1–2/1-6). In cohort A/B/C, the confirmed ORR was 15.4/15.4/0% [95% highest posterior density credible interval, 8.4–27.9/8.4–27.9/0.0–25.9]. The DCR, median (m) PFS, mOS were 57.7/53.8/22.2% [95% confidence interval (CI), 36.9–76.6/33.4–73.4/2.8–60.0], 2.7/1.8/1.4 months (95% CI, 1.5–4.1/1.4–9.3/1.0–2.8), 7.8/9.5/7.4 months (95% CI, 5.9–9.8/3.5–NE/2.9–8.6), respectively. In the pts with BRCA mutations by Guardant360 (cohort A/B/C were 18/21/8), ORR was 11.1/19.0/0% (95% CI, 2.0-30.2/6.5–38.3/0.0–28.3). The most common treatment-emergent adverse events were thrombocytopenia (31.1%), anemia (27.9%), neutropenia (14.8%), nausea (36.1%), fatigue (29.5%), anorexia (24.6%). Conclusions: Although niraparib had signs of clinical activity in pts with BRCA -mutated BTC and PC, the primary endpoint was not achieved statistically. No new safety signal was observed. Alternative approaches, such as evaluation in biomarker-selected patients or in combination with other agents, may demonstrate greater clinical activity of niraparib in this setting. Clinical trial information: jRCT2011200023.

Safety, tolerability, and preliminary efficacy of tinodasertib as a monotherapy or in combination with pembrolizumab or irinotecan in metastatic colorectal cancer: Interim results from a phase II open-label, dose-finding, run-in and cohort expansion study.

183 Background: MNK inhibition has been shown to downregulate phosphorylation at serine 209 of eIF4E, a potent regulatory point of CAP-mediated translation of 5’ polyadenylated mRNA associated with growth factor and pro-oncogenic signals in cells. Elevated levels of eIF4E phosphorylation are observed in a broad range of tumors. MNK1/2 knock out mice are healthy and viable, as cellular house-keeping mRNA translation occurs readily using the IRES mechanism, whereas mRNA with more complex and longer 5’ untranslated ends such as those involved in growth factor and pro-oncogenic signaling, are MNK activated. Cells from MNK knockout animals become relatively resistant to subsequent oncogenic transformation. In a program of SAD and MAD Phase I studies conducted in normal healthy volunteers, Tinodasertib was found to be safe and well tolerated with no dose-limiting toxicity (DLT). The objectives of this ongoing Phase 2 study are to evaluate safety, and preliminary efficacy of Tinodasertib as monotherapy and in combination with either pembrolizumab or irinotecan in patients with advanced colorectal cancer (CRC). Methods: Patients had to have advanced CRC and previously received ≥2 lines of therapy. The dose escalation phase of the study was open to all patients with CRC. As of 23 July 2024, 22 patients were dosed in a modified 3X3 dose escalation design with Tinodasertib from 20 to 80 mg on alternate days. Out of 22 patients, 12 received monotherapy, 4 were treated with Tinodasertib and Irinotecan and 6 were treated with Tinodasertib and pembrolizumab. Majority (19) had MSS CRC and 3 had unknown status. Nine patients had KRAS-mut CRC. Results: No DLTs were observed and MTD was not reached. Grade 3 treatment-related adverse events (TRAEs) were observed in 2 (9%) patients and were related to irinotecan while no Grade 3 AEs were attributed to Tinodasertib by either the investigator or the sponsor. Most common TRAEs were related to gastrointestinal system organ class. There were no Grade 4-5 TRAEs. Of the 22 patients, 18 were evaluable for RECIST 1.1 response. No patient had an objective response to treatment, 12 had stable disease with disease control rate of 67% and a progression free survival of 2.99 months. Patients remained on therapy for up to 28 weeks. Overall survival (OS) at 52 weeks was 52% (CI 29 to 93). Conclusions: Tinodasertib either as monotherapy or combined with irinotecan or pembrolizumab, was well tolerated with no DLTs at the dose levels evaluated. Prolonged median time to progression and OS compared to historical controls were observed even during the dose escalation phase for the study population as a whole and for each of the monotherapy and combination arms. Enrolment in the dose escalation phase continues. Clinical trial information: NCT05462236 .

Piezoelectric‐Enhanced Nanocatalysts Trigger Neutrophil N1 Polarization against Bacterial Biofilm by Disrupting Redox Homeostasis (Adv. Mater. 6/2025)

Linear Enhanced 3D Nanofluid Force‐Electric Conversion Device

AbstractThe inherent trade‐off between permeability and selectivity has constrained further improvement of passive linear force‐electric conversion performance in nanofluidic pressure sensors. To overcome this limitation, a 3D nanofluidic membrane with high mechanical strength utilizing aramid nanofibers/carbon nanofiber (ANF/CNF) dual crosslinking is developed. Due to the abundant surface functional groups of CNF and the high mechanical strength of ANF, this large‐scale integrated 3D nanofluidic membrane exhibits advantages of high flux, high porosity, and short ion transport path, demonstrating superior force‐electric response compared to conventional 1D and 2D configurations. The enhancement mechanism of the ANF/CNF membrane is systematically investigated through experimental results and theoretical calculations. The optimized device has a sensitivity of 111 nA cm−2 kPa−1, a response/recovery time of 63/68 ms, and a stability of 45 000 cycles. This study successfully overcomes the inherent performance limitations of traditional nanofluidic membranes, offering promising potential for applications across artificial intelligence, the Internet of Things, and smart wearable devices.

A randomized phase II trial of systemic chemotherapy with or without trastuzumab followed by surgery in HER2 positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: 3-year follow-up data of the Japan Clinical Oncology Group study JCOG1301C (Trigger study).

393 Background: We previously reported better objective and pathological response with the addition of trastuzumab to preoperative chemotherapy in the randomized phase II trial comparing the efficacy of systemic chemotherapy with or without trastuzumab followed by surgery in HER2 positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis. Here, we report 3-year follow-up data. Methods: Eligible patients with HER2-positive gastric cancer having extensive lymph node metastasis were randomized to receive preoperative chemotherapy with S-1/cisplatin (SP: S-1 80–120 mg/body on days 1–14, and cisplatin 60 mg/m2 on day 1, q21 days, 3-4 courses) in arm A or SP plus trastuzumab (first course 8 mg/kg followed by 6 mg/kg, day 1 on each course) in arm B. After gastrectomy, adjuvant chemotherapy with S-1 was added for 1 year in both arms. The primary endpoint was overall survival (OS), and the sample size was planned to be 130 patients in total, expecting a 10% increase in the 3-year OS (70% vs 80%) with a 1-sided alpha of 0.2, a power of 0.75. Results: The study was terminated in March 2021 due to slow patient accrual. In total, 46 patients were randomized to either arm A (22 patients) or arm B (24 patients). Patient characteristics were well balanced between the arms. Planned preoperative chemotherapy was completed in 20 patients (90.9%) in arm A and in 23 patients (95.8%) in arm B. Objective response rate tended to be higher in arm B (66.7% [16/24]) than in arm A (36.4% [8/22], p=0.08), and R0 resection was achieved in 20 patients (90.9%) in arm A and 22 patients (91.7%) in arm B. The adjuvant chemotherapy was completed in 54.6% (12/22) in arm A and in 54.2% (13/24) in arm B. With the median observation period of 4.1 years, the 3-year OS was 68.2% in arm A and was 78.9% in arm B with a hazard ratio of 0.698 (95% confidence interval (CI), 0.221-2.209). The 3-year progression-free survival of arm A and arm B was 39.3% and 62.3%, respectively, with a hazard ration of 0.562 (95% CI, 0.229-1.377). Conclusions: Preoperative chemotherapy with SP plus trastuzumab was feasible, and tended to improve the objective response rate, OS and progression-free survival. An integrated analysis with other clinical trials evaluating perioperative trastuzumab is being planned. Clinical trial information: s031180006.

Adjuvant Docetaxel and Cyclophosphamide With or Without Epirubicin for Early Breast Cancer: Final Analysis of the Randomized DBCG 07-READ Trial

The primary analysis of the DBCG 07-READ trial reported in 2017 provided evidence of no overall benefit from adjuvant anthracyclines in patients with early TOP2A normal breast cancer in disease-free survival (DFS), distant disease-free survival (DDFS), or overall survival (OS). We performed a protocol-scheduled analysis of DDFS, DFS, and OS on the basis of 10-year follow-up. Full details on incident heart failure (HF) and second cancers were presented. Patients in the intention-to-treat population assigned to epirubicin and cyclophosphamide followed by docetaxel (EC-D) had longer DDFS (adjusted hazard ratio [HR], 0.79 [95% CI, 0.64 to 0.98]; P = .03) and DFS (HR Adjusted , 0.83 [95% CI, 0.69 to 0.99]; P = .04) than patients assigned to docetaxel and cyclophosphamide (DC). There was no statistically significant difference in mortality rates. The 10-year cumulative risk of HF was 2.1% (95% CI, 1.4 to 3.3) with EC-D and 1.1% (95% CI, 0.6 to 2.0) with DC (HR Unadjusted , 2.12 [95% CI, 1.03 to 4.35]; P = .04). In conclusion, anthracycline followed by docetaxel improved outcome compared with DC in patients with TOP2A normal early breast cancer, and no clinical value of TOP2A testing was shown. The risk of HF was doubled in patients receiving anthracycline; however, overall, the risk of HF was low.