bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) versus endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for tissue sampling of solid pancreatic and non-pancreatic lesions without ROSE: a prospective multicenter study
Authors: Okasha Hussein Hassan , Ahmed Mohammed Yousri , Ahmed Marwa A. , Elenin Sameh Abou , Abdel-latif Abeer , Farouk Mahmoud , Ameen Mahmoud Gamal , El-Habashi Ahmed Hussein , Elshaer Mahasen Akram , Alzamzamy Ahmed Elsayed 
Published: June 2024

Abstract
Background and aims
Endoscopic ultrasound-guided tissue acquisition, including both fine-needle aspiration (EUS-FNA) and fine-needle biopsy (EUS-FNB), has been frequently performed to acquire samples from both pancreatic and non-pancreatic lesions. Still, the impact of the diagnostic yield between FNA and FNB is uncertain. We conducted this study to compare the diagnostic performance and accuracy of the 22-gauge FNA needles with the 22-gauge FNB needles in sampling solid pancreatic and non-pancreatic lesions.

Methods
This is a prospective multicenter study conducted on 465 cases presented with solid pancreatic or non-pancreatic lesions.

Results
Patients were 275 male and 190 females with a mean age of 59 years. Three-hundred twenty-seven patients had solid pancreatic lesions, while 138 had non-pancreatic lesions; 245 cases underwent EUS-FNA, and the remaining 211 cases underwent EUS-FNB. The presence of intact tissue core and sample adequacy was significantly higher in the FNB cases in solid pancreatic and non-pancreatic lesions. Blood contamination was significantly more in cell blocks and smears of EUS-FNA compared to that of EUS-FNB in solid pancreatic and non-pancreatic lesions. Based on histologic assessment of cell block only, EUS-FNB had more diagnostic accuracy (99%) than FNA (61%) (P-value < 0.005). However, cytological diagnosis by smears only showed no significant difference. The combined cytological and histological evaluation had 100% sensitivity, specificity, and accuracy.

Conclusion
EUS-FNA and EUS-FNB have comparable accuracy in diagnosing solid pancreatic and non-pancreatic lesions without ROSE. EUS-FNB is superior to EUS-FNA in acquiring intact tissue core and adequate samples with little blood contamination. Based on histological assessment (cell block/tissue core) only, EUS-FNA has less accuracy than EUS-FNB in diagnosing solid pancreatic lesions.
Safety and preliminary efficacy results of IBI389, an anti-CLDN18.2/CD3 bispecific antibody, in patients with solid tumors and gastric or gastro-esophageal tumors: A phase 1 dose escalation and expansion study.
Authors: Zheng Li , Ruihong Dai , Jieer Ying , Xu Qi , Guo Zengqing , Hu Changlu , Sun Yuping , Niu Zuoxing , Hao Jihui , Zhang Mingjun , Guanghai Dai , Hua Dong , Pan Yueyin , Wang Xin , Wei Shuqing , Chen Xiaobing , Yu Xinhe , Zhang Yulong , Zhou Hui , Bi Feng 
Published: June 2024

2519 Background: CLDN18.2 expression has been observed in various solid tumors especially in gastric cancer, indicating its potential as a novel target for anti-tumor therapy. IBI389 is an anti-CLDN18.2/CD3 bispecific antibody that induces immune synapse formations by linking CD3 molecules in T-cell receptor complexes and CLDN18.2 antigens on the membrane of tumor cells. Herein, we report preliminary results from a phase I study to evaluate safety and efficacy of IBI389 in patients (pts) with advanced solid tumors. Methods: Eligible pts with advanced solid tumors who failed or were intolerant to standard treatments were enrolled. The dose escalation of IBI389 monotherapy used intra-patient dose escalation with accelerated titration and the classic 3+3 design (0.003 µg/kg to 600 µg/kg). Selected dose levels were expanded in pts with advanced gastric/gastroesophageal junction cancer (G/GEJ C) and pancreatic ductal adenocarcinoma (PDAC). The primary objective was safety. Secondary objective was efficacy assessed by investigator per RECIST v1.1 including objective response rate (ORR) and disease control rate (DCR). Results: As of January 9, 2024, a total of 114 pts were enrolled (males: 67.5%, median age: 60.0 years, G/GEJ C: 32.5%, PDAC: 57.9%, stage IV: 81.6%). No dose-limiting toxicity (DLT) was observed during dose escalation. The MTD was not reached. In all pts, treatment-emergent adverse events (TEAEs) occurred in 112 (98.2%) pts including 76 (66.7%) pts with grade ≥3 TEAEs. Treatment-related adverse events (TRAEs) occurred in 111 (97.4%) pts including 63 (55.3%) pts with grade ≥3 TRAEs. The most common grade ≥3 TRAEs (≥ 4%) were gamma-glutamyl transferase increased (21.9%), lymphocyte count decreased (13.2%) and nausea (4.4%). Cytokine release syndrome (CRS) related adverse events occurred in 65 (57.0%) pts including 1 (0.9%) pts with grade 3 CRS and no grade 4 or 5 CRS. TEAEs leading to dose interruption and treatment discontinuation occurred in 44 (38.6%) and 8 (7.0%) pts. Preliminary efficacy of IBI389 was observed in pts with CLDN18.2 expression ≥10% (immunohistochemistry 2+/3+). In G/GEJ C pts with previous treatments ≥2 lines receiving IBI389 at various dose levels ranging from 10µg/kg to 600 µg/kg (n=26), 8 pts had partial response (PR) and 11 pts had stable disease (SD). The ORR was 30.8% (95%CI: 14.3-51.8) and DCR was 73.1% (95%CI: 52.2-88.4). Conclusions: IBI389 showed manageable safety profiles in pts with advanced solid tumors and preliminary efficacy in CLDN18.2-positive pts with G/GEJ C. Clinical trial information: NCT05164458 .
Safety and preliminary efficacy of EIK1001 in combination with pembrolizumab in participants with advanced solid tumors.
Authors: Tolcher Anthony W. , Rasco Drew W. , Johnson Melissa Lynne , Patel Manish R. , Alistar Angela Tatiana , Cohen Julia Wanda , Cho Carolyn , Wang Meihua , Kurland Etah 
Published: June 2024

2521 Background: Immune checkpoint inhibitors (ICIs) relieve immunosuppression of tumor-reactive T cells and enhance antitumor immune response; however, not all patients benefit and some become refractory. EIK1001 is a Toll-like receptor (TLR)7/8 agonist that stimulates myeloid and plasmacytoid dendritic cells, activating immune and inflammatory responses. This dual activity provides another pathway, distinct from effects on checkpoint proteins, to enhance antitumor T-cell activity alone or in combination with ICIs. Methods: Study BDB001-101 was a Phase 1, open-label, dose-escalation/expansion study of EIK1001 as either monotherapy (mono Rx; previously reported) or combined with pembrolizumab (comb Rx). Enrollment criteria included participants (pts) ≥ age 18 with confirmed, RECIST-measurable advanced solid tumors. Primary study objectives included safety and tolerability, and secondary objectives included evaluation of dose-limiting toxicities, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy by RECIST 1.1. During comb Rx dose escalation, pts received a range of doses of EIK1001 (QW IV) in combination with pembrolizumab (200 mg Q3W). Results: Fifty-one pts (median age 67 [range 33 to 86]) with multiple, distinct histological tumor types and with a median of 3 prior Rx regimens were enrolled. Overall, a total of 42/51 (82.4%) comb Rx pts experienced a treatment-related adverse event (TRAE). A total of 9/51 (17.7%) experienced a ≥ Grade 3 TRAE, including fatigue, cytokine release syndrome (CRS), hemiparesis, hypertension, joint range of motion reduced, muscular weakness, pancreatitis, rash (maculopapular), skin plaque, and stomatitis. Overall, 5/51 (9.8%) experienced manageable CRS, with only 1 discontinuation due to CRS. There were no deaths due to TRAEs. Of the efficacy-evaluable pts (n = 50), complete response (CR) or partial response (PR) was observed for 7/50 (14.0%), including 3 CR and 4 PR. Disease control (including CR, PR, or stable disease) was observed in 24/50 (48.0%). The median duration of response was 10 months (range = 4 to 32 months). Responses were observed in pts with prior anti-PD-1 exposure as well as in those with low or negative PD-L1 tumor expression. EIK1001 PK was linear and dose-proportional, and combination with pembrolizumab did not affect EIK1001 PK. Conclusions: Overall, EIK1001 was well-tolerated with a manageable safety profile and showed encouraging preliminary efficacy across several tumor types in combination with pembrolizumab. Responses were observed even in heavily pretreated patients not anticipated to respond to pembrolizumab monotherapy. Further development of EIK1001 is underway. Clinical trial information: NCT03486301 .
The gut microbial characteristics and underlying mechanisms of patients with different clinical prognoses from immunotherapy by landmark analysis.
Authors: Liu Xinyu , Lu Bo , Jia Xinmiao , Tang Hao , Zhou Qingyang , Zeng Yanlin , Gao Xiaoxing , Chen Minjiang , Xu Yan , Wang Mengzhao , Qian Jiaming , Tan Bei 
Published: June 2024

2606 Background: A subset of cancer patients could benefit long-termly from immune checkpoints inhibitors (ICIs), which was called smearing effect. Gut microbiota was widely found to be associated with the initial ICIs efficacy and immune-related adverse event (irAE). This study aimed to identify the baseline gut microbiota characteristics of long-benefit patients and explore the possible underlying mechanisms. Methods: Lung cancer patients initially treated with anti-PD-1/PD-L1 therapy were consecutively enrolled from May 2020 to September 2022. All patients were classified into Benefit group, Resistance group and Severe irAE group based on the long-term prognosis. The baseline gut microbiota characteristics were identified by metagenome sequencing. MelonnPan was used to predict the abundances of 79 metabolites. The sequences of autoantigen, lung cancer antigen and anticancer peptides (ACPs) from IEDB and CancerPPD databases were aligned against the scaftigs of fecal samples. Results: 54 patients were enrolled with 24 in Benefit group, 13 in Severe irAE group and 17 in Resistance group. The microorganism composition was significantly different between Benefit group and Resistance group ( P=0.03), while no difference between Benefit group and Severe irAE group ( P=0.93). The co-occurrence network showed the Benefit group patients had the most compact microbiota network. Metabolites prediction analyses showed the short chain fatty acids propionate ( P=0.005) and butyrate/isobutyrate ( P=0.03) were significantly enriched in Benefit group than Resistance group, wherein the acetyl-CoA pathway ( P=0.04) accounted for the largest proportion of butyrate-production ability difference. The beneficial species had more positive correlations with butyrate-producing enzymes ( P<0.001). The microbiota of irAE patients had abundant aligned sequences with antigen epitopes of multiple autoimmune diseases. The total counts of systemic lupus erythematosus-related epitopes were significantly more enriched in patients with immune-related colitis ( P=0.04), especially FDNGRRGRPVTGP ( P=0.02) and IDNGRRGRPITGP ( P=0.02). Likewise, the microbiota of patients with good ICIs efficacy tended to have more abundant cancer-related antigen counts ( P=0.07) and ACPs counts ( P=0.06). Strain-level analysis revealed Escherichia coli and Faecalibacterium prausnitziishowed a centralized trend of genomic variations based on different clinical phenotypes. Conclusions: Long-term benefit patients had converging characteristics of gut microbiota, which coevoluted a compact microbial community with high butyrate-producing ability. The microbiota molecular mimicry of autoimmune and tumor antigen might contribute to irAE and ICIs efficacy. The strain-level genomic variations of specific species may also play a role in clinical phenotypes.
Phase Ia/Ib trial on the safety and efficacy of mobocertinib in combination with T-DM1 for patients with HER2-mutant solid tumors (WJOG16022M).
Authors: Kanemura Hiroaki , TANIZAKI JUNKO , Matsumoto Koji , Masuishi Toshiki , Isobe Taichi , Kodama Hiroaki , Shimizu Toshio , Sunakawa Yu , Chiba Yasutaka , Yamamoto Nobuyuki , Nakagawa Kazuhiko , Hayashi Hidetoshi 
Published: June 2024

3025 Background: Safety and efficacy of HER2 tyrosine kinase inhibitor (TKI) and anti-HER2 antibody-drug conjugate (ADC) in HER2-mutant solid tumors have not been investigated. Methods: Mobocertinib, a potent HER2 TKI plus T-DM1, an anti-HER2 ADC was evaluated in this phase I study. In a dose-finding cohort (phase Ia, pIa), the maximum tolerated dose was estimated in patients (pts) irrespective of HER2 mutational status. To further establish safety and evaluate preliminary efficacy, additional pts with HER2 mutations were enrolled in a dose-expansion cohort (phase Ib, pIb). Mobocertinib of 80, 120 to 160 mg was orally administered with intravenous T-DM1 3.6 mg/kg every 3 weeks. The primary endpoint was to determine the recommended dose (RD) (pIa), and to evaluate the confirmed objective response rate (ORR) (pIb). Results: Between Nov 2022 and Jun 2023, a total of 28 pts, 6 in the pIa and 22 in the pIb were enrolled to this study (14 NSCLC; 4 cervical; 2 duodenal papilla; 2 pancreatic, median follow-up, 6.4 mo [range, 1.9 to 12.9 mo]). The median age was 54 (range, 40-84) years, 17 pts were female. Among 27 pts with HER2-mutant tumors, mutations in kinase domain were most common (66.7%). In the pIa cohort, 3 DLTs were observed with mobocertinib 120 mg, including grade 3 thrombocytopenia, grade 4 acute kidney injury, and drug withdrawal due to nausea and anorexia, while there was no DLT with 80 mg. The RD was therefore determined to be mobocertinib 80 mg plus T-DM1 3.6 mg/kg. Among 22 pts in the pIb, grade ≥ 3 AE occurred in 72.7% of pts; the common events (>5%) being thrombocytopenia (50.0%), diarrhea (13.6%), and anorexia (13.6%). No interstitial lung disease/pneumonitis was observed. The ORR was 28.6%, the disease control rate (DCR) was 71.4%, and median progression-free survival (mPFS) was 3.2 mo (95% CI 1.6, 6.1) in the pIb. In 27 pts with HER2 mutations across all cohorts, the ORR was 42.3%, the DCR was 76.9%, and mPFS was 4.3 mo (95% CI 2.7, 6.7). Additionally, in 13 pts with HER2-mutant NSCLC including those who had developed resistance to trastuzumab deruxtecan, the ORR was 53.8%, the DCR was 84.6%, and mPFS was 6.1 mo (95% CI 2.9, 6.3). Conclusions: The RD of this study treatment is mobocertinib 80 mg plus T-DM1 3.6 mg. Combination therapy of HER2 TKI and HER2 ADC demonstrated feasibility and potential efficacy for HER2-mutant solid tumors. Clinical trial information: 2051220070 .
The anti-CD20 antibody-drug conjugates TRS005 in relapse/refractory CD20-positive B-cell non-Hodgkin lymphoma: A multicenter, open-label, single-arm, phase I study.
Authors: Shi Yuankai , Li Zhiming , Qin Yan , Li Yufu , Zhou Keshu , Zhang Huilai , Li Ling , Jia Youchao , Tong Xiangmin , Liang Xinquan , Zhang Yongdong , Li Kunyan , Zhou Hui , Hou Shuling , Li Zengjun , Shuang Yuerong , Liu Peng , Gui Lin 
Published: June 2024

3026 Background: TRS005 is a novel anti-CD20 antibody-drug conjugate targeting CD20 positive tumor cells to deliver MMAE into the cells via receptor-mediated endocytosis. The aim of this study was to evaluate the safety, pharmacokinetics, and anti-tumor activity of TRS005 in relapse/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). Methods: This first-in-human, single arm, multicenter, phase I, dose-escalation and expansion study conducted at 28 hospitals in China. The eligible patient had histologically confirmed CD20 positive B-cell lymphoma and had failed ≥2 prior lines of standard treatment. The dose-escalation phase involved 6 dose cohorts (from 0.1mg/kg to 2.1mg/kg) following a 3+3 design. Patients received TRS005 intravenously on day 1 of each 21-day cycle for 6 cycles. The dose cohort in which partial response (PR) or complete response (CR) was observed entered the dose-expansion phase. The safety, tolerability and efficacy of TRS005 were evaluated every two cycles. The primary endpoints were safety and pharmacokinetics. Secondary endpoints were objective response rate (ORR), disease control rate (DCR) and progression free survival (PFS) assisted by investigators. Results: From Aug 24th,2020 to Oct 23th,2023, 130 R/R B-cell NHL patients received treatment. The dose limiting toxicity was observed in the first patient in the 2.1mg/kg dose group during the dose-escalation phase. 70 patients had R/R diffuse large B cell lymphoma (DLBCL). Of the 70 R/R DLBCL patients, the median age was 59 (25-83) years, 82.9% of patients were in stage III-IV and 98.6% of patients received at least 2 lines of treatment (except one patient who only received 1 line of previous treatment). Overall, 88.6% of patients experienced all grades adverse events (AEs). Treatment-emergent adverse events (TEAEs) of ≥grade 3 occurred in 65.7% of patients, hematologic TEAEs were the most common. Two patients withdraw the treatment due to TEAEs and no TEAE related death were observed. At the data cutoff date of Nov 17th, 2023, the median treatment duration was 4 (1-27) cycles. 58 patients were evaluated for efficacy and confirmed ORR was 46.6%, with a DCR of 75.9%. The highest ORR was seen in 1.8mg/kg dose cohort, with an ORR and DCR of 56.7% and 86.7%, respectively. The PFS was 5.6 (95% CI: 4.2-17.4) months and 12-month PFS was 35.1%. Conclusions: TRS005 is well-tolerated and exhibits encouraging anti-tumor efficacy in the treatment of R/R DLBCL. Clinical trial information: NCT05395533 . [Table: see text]
A phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation.
Authors: Stockton Shannon , Shyr Cathy , Cecchini Michael , Aljumaily Raid , Halfdanarson Thorvardur Ragnar , Sonbol Mohamad B. , Whisenant Jennifer , Ivy S. Percy , LoRusso Patricia , Das Satya , Gore Steven , Berlin Jordan , Beumer Jan Hendrik , Heumann Thatcher Ross 
Published: June 2024

3076 Background: Ataxia telangiectasia and Rad3-related (ATR) protein kinase is activated by replication stress and recruited to stalled forks or single strand DNA abnormalities in various cancers. The topoisomerase-I (Top1) inhibitor topotecan induces DNA damage. The ATR inhibitor BAY 1895344 (elimusertib) has demonstrated cytotoxic potential in small cell lung cancer and gastrointestinal cancer xenografts when combined with Top1 inhibitors . Methods: This is phase Ia study of elimusertib combined with topotecan in adult patients with refractory advanced solid tumors for whom topotecan can be considered as part of standard care. Patients with previous topotecan exposure were excluded. The study combination was assessed starting at Topotecan 1 mg/m2 IV (D1-D5) plus elimusertib 20 mg BID (D2, D5) (Cycle=21 days). Dose escalation utilized a 3+3 design. Primary objectives were to assess safety and tolerability and estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination. Secondary objectives included estimating pharmacokinetic (PK) profiles and assessing anti-tumor activity of the combinations. Results: Eight patients were treated in dose escalation. Participants were a median of 63 years old and had received 2 median lines of previous therapy. The initial two patients enrolled into dose level (DL) 1 had dose-limiting toxicities with one of patient experiencing respiratory failure and cardiac arrest in setting of pancytopenia related to study drug. Six patients were subsequently enrolled in and received DL-1 (elimusertib decreased from 20 mg BID to 20 mg Daily) and no DLTs were observed. Notable grade 3+ treatment-related adverse events and summary best response are summarized in Table. Disease control rate was 43% among evaluation patient including one unconfirmed partial response. Median progression-free survival in the RP2D cohort was 3.45 months. PK studies are in process and results will be presented at time of meeting. Conclusions: RP2D and MTD was established for elimusertib in combination with Topotecan: Topotecan 1 mg/m2 IV [D1-D5] plus elimusertib 20 mg Daily [D2, D5] every 3 weeks. Dose escalation was notably limited by myelotoxicity. Due to sponsor decision, the study was halted prior to planned expansions cohorts but the concept of ATR + topo I inhibition remains relevant. Clinical trial information: NCT04514497 . [Table: see text]
Biomarker discordance after neoadjuvant systemic therapy and associated patterns of recurrence.
Authors: Chong Esther G , Joung Bowon , Guo Mengni , Jeon Won Jin , Bera Kevin , Lee Jae , Moon Jin Hyun Floyd , Nagaraj Gayathri 
Published: June 2024

3149 Background: Understanding and addressing intratumor heterogeneity in breast cancer (BC) is crucial for advancing research and improving patient outcomes. The identification of biomarkers for targeted therapies is complex when dealing with heterogeneous tumors, and this heterogeneity complicates cancer outcomes since it affects treatment response, and the development of resistance. Methods: A single institution retrospective review of patients with BC who received neoadjuvant systemic therapy (NAST) followed by definitive surgical resection from 2008 to 2022 was performed. Initial tumor biopsies were tested for hormone receptors (HR) [estrogen receptor (ER) and progesterone receptor (PR)], and HER2 status and repeated on the residual tumor tissue after NAST. HER2 status was categorized into HER2-negative, HER2-low, and HER2-positive and HR status was categorized into ER and/or PR positive or negative based on the 2023 ASCO-CAP guidelines. HER2 and HR concordance and discordance rates were obtained and patients who had disease recurrence were identified and analyzed using descriptive statistics and Fisher’s exact test. Results: 480 patients with BC received NAST, and 143 patients with residual disease had pre and post treatment biomarker data available for analysis with a median post-surgery follow up of 15.2 months. Discordance in either HER2 or HR status was identified in 50% (72/143) of samples. Out of 143 patients, 44 patients had disease recurrence in which 50% (22/44) of tumors exhibited biomarker discordance. Among the changes in biomarker status, a shift in PR expression occurred most frequently in 27% of tumors (12/44). A change from HER2-low to HER2-negative status, as well as changes in ER expression occurred in 11% of tumors (5/44). 14% (6/44) of tumors had changes in both HER2 and HR. In patients who did not have recurrence, 51% (50/99) of tumors exhibited biomarker discordance. A HER2-low to HER2-negative status occurred most frequently in 18% (18/99). A change in ER expression occurred second most frequently, in 14% (14/99) of tumors. There was no statistical significance of discordance rates in the recurrence group and non-recurrence group (p-value=0.96). Conclusions: Tumor heterogeneity plays a role in shaping the distinct tumor biology of each patient. While the rates of biomarker discordance were comparable between samples with and without recurrence, the importance of HR discordance in this group requires extensive long-term monitoring. Our research highlights the importance of biomarker changes in a curative setting. Considering the implications for treatment, further investigation into additional biological and tumor-related factors associated with recurrence is warranted. [Table: see text]