tbuckley/cabot-search huggingface dataset:
Results of a phase 2 trial of ramucirumab plus docetaxel as second-line treatment for patients with advanced gastric cancer (HGCSG 1903).
Authors: Kentaro Sawada, Yasuyuki Kawamoto, Kazuaki Harada, Takayuki Ando, Susumu Sogabe, Yoshimitsu Kobayashi, Masayoshi Dazai, Michio Nakamura, Kazuteru Hatanaka, Atsushi Ishiguro, Atsushi Sato, Shintaro Nakano, Yoshiaki Shindo, Ayumu Hosokawa, Ken Ito, Ayumu Yoshikawa, Kayoko Iuchi, Isao Yokota, Satoshi Yuki, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2025)

447 Background: Ramucirumab (RAM) has shown efficacy in combination with paclitaxel (PTX) or irinotecan in the second-line treatment of advanced gastric cancer (AGC). However, the efficacy and safety regarding the combination therapy of RAM and docetaxel (DTX) have not been reported. We hypothesized that RAM plus DTX for patients with AGC could be as effective as RAM plus PTX and could reduce the incidence of neuropathy. Methods: HGCSG 1903 was a non-randomized, single arm, phase 2 trial carried out at 20 institutes in Japan. AGC patients with refractory or intolerance to primary chemotherapy were eligible. RAM (8 mg/kg on day1 and 15) plus DTX (60 mg/m 2 on day1) combination therapy administered in 28-day cycle were continued until disease progression or emergence of adverse events requiring discontinuation. The primary endpoint was response rate (RR) with threshold value of 10.7% and an expected value of 27.9%. A total of 35 cases are planned for registration. The secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. This trial was registered with Japan Registry of Clinical Trials, number jRCTs011200010. Results: Between Nov 2020 and Dec 2023, 36 patients were enrolled. Median age was 70 (range, 36–82); female/male were 7/29; ECOG PS 0/1, 16/20, respectively. One patient did not initiate study treatment at the onset of bowel obstruction after enrollment. In the efficacy and safety analysis set of 35 patients, RR was 25.7% (95%C.I., 12.5–43.3%) and disease control rate was 74.3% (95%C.I., 56.7–87.5%). Median OS and PFS were 11.9 months (95%C.I., 3.0–20.7) and 3.1 months (95%C.I., 2.1–4.2), respectively. Grade 3 or higher adverse events that occurred in more than 5% of patients were neutropenia (68.6%), leucopenia (57.1%), febrile neutropenia (17.1%), hypertension (14.3%), anorexia (11.4%), anemia (8.6%), and fatigue (5.7%). Grade 4 neutropenia occurred in 60.0% of patients. The protocol was amended to allow primary G-CSF prophylaxis during study period. The number of patients who received primary G-CSF prophylaxis after the amendment was 7/13 (53.8%). Neuropathy occurred in 65.7% of all grades, with no incidence of grade 3 or higher. No death and new safety signals with a causal relation to study treatment were observed. Conclusions: The primary endpoint of response rate was met in HGCSG 1903. Although neutropenia and febrile neutropenia may be more frequent, they were manageable. RAM plus DTX might be considered as an option for second-line treatment of patients with AGC. Clinical trial information: jRCTs011200010.
The efficacy of anamorelin in gastrointestinal cancer with cancer cachexia: Single center experience.
Authors: Yuka Suzuki, Atsuo Takashima, Toshiharu Hirose, Hirokazu Shoji, Hidekazu Hirano, Natsuko Tsuda Okita, Ken Kato
Journal: Journal of Clinical Oncology (2025)

815 Background: Cancer cachexia is a catabolic syndrome that causes weight loss and loss of appetite in cancer patients. Anamorelin (ANAM) is an oral drug approved in Japan to treat cancer cachexia by selectively activating ghrelin receptors. There is limited real-world data available on the efficacy of ANAM for patients with gastrointestinal cancer. We assessed its efficacy and identified associated clinical features. Methods: We retrospectively collected data from medical records and questionnaires on gastric and colorectal cancer patients who received ANAM between April 2021 and March 2023. We evaluated the change in body weight, appetite, and oral intake from the time of initiation of ANAM. We judged the responder who gained more than 0.5 kg in body weight, improved appetite, and increased oral intake, respectively. The association between clinical features and the responders was also assessed using multivariate logistic regression analysis. Results: 72 patients were included in this study. Characteristics of the patients: median age: 68 years old (range 38-85), male/female: 35/37, gastric/colorectal cancer: 39/33, PS 0-1/2 or more: 63/9, median body mass index (BMI): 18.0 kg/m 2 (range 12.3-27.9), number of prior chemotherapy regimens 1/2/3 or more: 17/22/33, ascites none/mild/moderate/severe: 42/19/7/4, median serum albumin levels (Alb): 3.2 g/dl (range 2.0-4.2). The median treatment duration of ANAM was 47.5 days (3-450 days). 57 patients (79.2%) continued ANAM for more than 3 weeks, and 9 patients for more than 12 weeks. The main reasons for discontinuation were progressive disease (39.7%), ineffective (12.7%), effective (11.1%) and adverse events of ANAM (11.1%). 33 patients (45.8%) gained weight, 41 patients (56.9%) improved appetite and 34 patients (47.2%) increased oral intake. There was a correlation found between BMI ＜ 18.0 kg/m 2 and the responders (OR 3.43, p = 0.041). Conclusions: In this study, 68.0% of patients who received ANAM for showed response, that is, gained body weight, or improved appetite, or increased oral intake. And these observations suggested that BMI was associated with effects of ANAM. Further studies involving more patients needed.
A phase 1/2 study evaluating the safety and efficacy of autologous TAC T cells in subjects with claudin 18.2+ advanced solid tumors.
Authors: Ecaterina Elena Dumbrava, Syma Iqbal, Simon Turcotte, Gregory P. Botta, Benjamin L. Schlechter, Geoffrey Yuyat Ku, Peter Joel Hosein, Samuel Saibil, Miriam Gavriliuc, Maria Apostolopoulou, Mobolaji Giwa, Kara M. Moss, Swaminathan Murugappan, Davendra Sohal
Journal: Journal of Clinical Oncology (2025)

828 Background: Claudin18.2 (CLDN18.2) is a tight junction protein found in gastric epithelial cells. It can become abnormally expressed in gastric cancer and other solid tumors, rendering it a candidate for targeted therapy. There are no approved therapeutic agents against CLDN18.2. The T cell antigen coupler (TAC) technology modifies T cells ex vivo , allowing cytotoxicity of tumor cells by co-opting the natural T cell receptor. TAC T cells demonstrate a safer profile than chimeric antigen receptor T cells. TAC01-CLDN18.2 is an autologous T-cell product comprising T cells expressing CLDN18.2 TAC. Methods: In this first-in-human study (NCT05862324), subjects will undergo leukapheresis and may receive bridging anticancer therapy during cell manufacturing. Prior to TAC01-CLDN18.2 infusion, subjects will undergo lymphodepletion chemotherapy. In Phase I, TAC01-CLDN18.2 will be administered at increasing doses (3 cohorts) in adult subjects with ≥2 lines of prior therapy (1 for subjects with pancreatic ductal adenocarcinoma (PDAC)) using the classic 3+3 dose escalation study design. CLDN18.2 expression levels will be determined centrally using a validated clinical trial assay. Dose-limiting toxicities (DLTs) will be assessed up to 28 days after the infusion. A second dose may be administered according to preidentified clinical and safety criteria. In Phase II, dose expansion groups will evaluate the efficacy, safety, and pharmacokinetics of the optimal TAC01-CLDN18.2 dose, with the option of redosing. Indications will include gastric and esophageal adenocarcinoma (group A), PDAC (group B) and ovarian and non-small cell lung cancer (group C) in subjects with &lt;4 lines of prior therapy. Results: The first two dose cohorts of Phase I have been completed, with no reported dose-limiting toxicities (DLT). All of the TAC-related adverse events were low-grade. No cytokine release syndrome was reported. One subject in cohort 2 experienced a grade 1 neurotoxicity, which resolved the same day without intervention. Six subjects reported a total of 6 serious adverse events, none related to TAC01-CLDN18.2. An 83.3% disease control rate was observed at first tumor assessment (Day 29). One subject in cohort 1 with heavily pre-treated PDAC (3 prior lines) with high CLDN18.2 expression has an ongoing, confirmed partial response. The subject received a second dose and is still on treatment (6 months). Conclusions: Treatment with the lower doses of TAC01-CLDN18.2 is safe and shows promising clinical activity in a heavily pre-treated cancer population. Treatment of cohort 3 has begun. Clinical trial information: NCT05862324 .
Impact of baseline alterations in HER2-pathway oncogenic drivers on response to anti-HER2 therapy in patients (pts) with HER2-amplified advanced colorectal cancer (aCRC).
Authors: Celine Hoyek, Angelo Pirozzi, Binbin Zheng-Lin, Oluseyi Abidoye, Cody Eslinger, Yoshiaki Nakamura, Ryne Ramaker, Mohamad Bassam Sonbol, Christina Wu, Mitesh J. Borad, Daniel H. Ahn, Masafumi Ikeda, Taro Shibuki, Takayuki Yoshino, John H Strickler, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2025)

243 Background: HER2-amplified aCRC is associated with poor prognosis despite new anti-HER2 regimens. Insight on biomarkers that predict response to these therapies is limited. This study aims to evaluate whether baseline alterations in oncogenic drivers along the HER2 pathway predict response to anti-HER2 therapy in HER2-amplified aCRC. Methods: In this international multi-center study involving Mayo Clinic, Duke Cancer Institute and National Cancer Center Hospital East (Japan), we collected baseline genomic alterations from tissue or blood samples using next-generation sequencing (NGS) prior to anti-HER2 therapy initiation. We defined PIK3CA, RAS, RAF, MAP2K, and MET as oncogenic drivers of resistance within the HER2 pathway. Overall survival (OS) was evaluated with the Kaplan-Meier method and a log-rank test was used to compare median OS (mOS) between pts with and without alterations in the above genes. A chi-square test (significance level 0.05) was performed to compare overall response rate (ORR) and disease control rate (DCR). Results: We identified 39 pts with HER2-amplified aCRC and baseline NGS. Median age was 57 (range 30-77), 54% were male. Baseline alterations in HER2 pathway oncogenic drivers were identified in 17 pts (43.5%). 18 (46%) received monoclonal antibodies (mAbs) plus tyrosine kinase inhibitors, 12 (30%) received dual mAbs and 7 (18%) received trastuzumab deruxtecan. The mOS was 41.9 months (mos) (95%CI 23.7-60.1) for other alterations vs 24.2 mos (95%CI 14.1-34.3) in pts with HER2 pathway alterations (p = 0.1). ORR was 47% vs 41% (p = 0.7) and DCR 82% vs 73% (p = 0.4), for pts with HER2 pathway alterations and without HER2 pathway alterations, respectively. 4 pts receiving trastuzumab/tucatinib had complete response, none of which had HER2 pathway alterations. Conclusions: Pts with baseline alterations in oncogenic drivers of the HER2 pathway had clinically worse outcomes compared to pts without such alterations despite receiving HER2-targeted therapy, though results lacked statistical significance. Larger studies are needed to confirm the lack of benefit from anti-HER2 therapy in this subgroup.
Preliminary results of benmelstobart plus anlotinib combined with SOX in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma with low PD-L1 expression: A single-arm, multicenter phase II clinical trial.
Authors: Yong-Xu Jia, Zhiwei Chang, Ya-Li Zhong, Donghai Cui, Hui-Qiong Han, Ya-Ping Gao, Jian He, Xiao-Lei Liu, Jie Yan, Yanru Qin
Journal: Journal of Clinical Oncology (2025)

444 Background: First-line chemotherapy for advanced HER2-negative gastric/gastroesophageal (G/GEJ) adenocarcinoma has limited efficacy. PD-1 inhibitors plus chemotherapy show promise but need improvement, especially for patients (pts) with low PD-L1 expression. Anlotinib, a multi-targeted TKI for tumor angiogenesis/proliferation, is approved in China. This study aims to evaluate the efficacy and safety of benmelstobart a PD-L1 blockade) in combination with anlotinib and SOX (S-1 plus oxaliplatin) as a first-line regimen for advanced G/GEJ adenocarcinoma in patients with low PD-L1 expression, Preliminary findings will be reported promptly. Methods: Pts with HER2-negative, unresectable, locally advanced, or metastatic G/GEJ adenocarcinomas and a PD-L1 Combined Positive Score (CPS) &lt; 5, who had not received prior systemic therapy were included. They received benmelstobart (1200mg, iv, d1, q3w) combined with anlotinib (10mg, po, d1~14, q3w), oxaliplatin (130mg/m 2 , d1, iv, q3w) and S-1 (40mg, po, bid, d1~14, q3w) for 6 cycles as initial therapy. Maintenance therapy with benmelstobart (1200mg, iv, d1, q3w) plus anlotinib (10mg, po, d1~14, q3w) followed for non-progressive diseaseuntil PD or unacceptable toxicity occurred. Tumor responses were evaluated by RECIST 1.1 criteria. The target sample size was 37, with ORR as the primary endpoint, and safety, DCR, DoR, PFS, and 1-year OS rate as secondary endpoints. Results: From Jun 2023 to Sep 2024, 28 pts were enrolled and 27 were available for efficacy and safety evaluation. The patients’ characteristics were as follows; median age (range): 59 (38-77) years, Male/Female: 19 (70%)/8 (30%), ECOG PS 0/1: 2 (7%)/25 (93%), Surgical history yes/no: 6 (22%)/21 (78%), CPS: ＜1/ ≥1: 4 (15%)/23 (85%), respectively. In the response assessment, 19 PR (70.4%), 6 SD (22.2%), and 2 NE (7.4%) were observed, yielding an ORR of 70.4% (95% CI: 49.8-86.2) and DCR of 92.6% (95% CI: 75.7-99.1). As of September 17, 2024, 6 of 27 patients discontinued (3 due to PD, 3 voluntary), leaving 21 ongoing. The longest DoT was 15.08 months, and the median PFS was not reached. Common TEAEs ≥10% included thrombocytopenia (37%), anemia (33%), leukopenia (22%), HFS (19%), fatigue (15%), liver function abnormalities (15%), and appetite loss (11%). Grade ≥3 TEAEs were thrombocytopenia (4%) and anemia (4%). Conclusions: Preliminary findings indicate that the combination of benmelstobart and anlotinib with the SOX regimen as a first-line treatment for advanced G/GEJ adenocarcinoma with low PD-L1 expression demonstrates promising therapeutic efficacy and tolerable adverse events. Further validation of these results in a larger, consecutive patient population is warranted. Clinical trial information: ChiCTR2400085396.
Clinical results of a phase 1 trial evaluating a HER2 directed CAR-T product selective for the tumor microenvironment (TME) in patients with GI and other solid tumor malignancies.
Authors: Yuhong Zhou, Qian Li, Wei Li, Lili Lu, Shuxiu Xiao, Yijun Cai, Lintao Liu, Gregory Ian Frost, Wendy Li
Journal: Journal of Clinical Oncology (2025)

449 Background: A major limitation of CAR-T in solid tumors has been the inability to safely target antigens shared between healthy and malignant tissue. One approach to improving selectivity is to regulate CAR affinity through the unique metabolism of the tumor microenvironment (TME). This first in human trial evaluated an autologous (41BB) CAR-T product encoding a tumor metabolism regulated HER2 CAR. Methods: This Phase 1, dose escalation, basket trial evaluated the safety, tolerability, pharmacokinetics and efficacy in 12 patients (pts) with HER2 IHC 3+ / FISH + Stage IV r/r solid tumor malignancies (gastric, esophageal, colorectal, breast). They had failed multiple lines of therapy (66.7% patients had failed 4~10 lines of therapies previously). Dose cohorts of 3E5 (n=3), 1E6 (n=3), or 1E7 (n=6) CAR-T cells/kg were evaluated with a 28-day in-patient DLT observation period. Cell product was manufactured from whole blood, with a 12-day closed process and release on day 17. Lymphodepletion regimen was 500 mg/m 2 Cy and 30 mg/kg 2 Flu X 3 prior to infusion of CAR-T. Results: Data cutoff 09/16/24. All 12 patients were evaluable for safety and efficacy. No DLTs, ICANS or SAEs were observed. For HER2 positive normal tissues of special concern (e.g. cardiomyocytes), longitudinal functional, biochemical and clinical cardiovascular tests showed no signs of OTOT. One patient experienced Grade 2 CRS and recovered. No AE’s lead to study discontinuation. In one patient, there were two Grade 3 AEs attributed to product (neutropenia and hypoxia); both which resolved. With a median follow-up of 302 days for cohort 3, 12-month survival rate in this cohort is 83.3%, compared to the 12-month survival rate of 33.3% for cohorts 1 and 2 combined. Encouraging signals of efficacy were observed with an ongoing (at 24 wks) deep PR (100% reduction SLD) in a GC patient. The median peak copy number of CAR-T cells in peripheral blood (n=12) was 1,818 copies/µg DNA (range 403 – 10,466). Conclusions: The tumor metabolism regulated HER2 CAR-T product was generally well tolerated, with no DLTs, and evidence of radiologic objective response in patients with gastroesophageal cancer. Combined, the safety and activity observed in this study suggests that a previously challenging solid tumor antigen may be safely targeted by a CAR with affinity regulated by the metabolism of the TME. Enrollment for the study was complete as of 28-Feb-2024 (NCT04511871). Clinical trial information: NCT04511871 .
Optimizing clinical trial design to mitigate racial disparities in pancreatic cancer clinical trial enrollment.
Authors: Tracey Pu, Alexandra M. Gustafson, Kendra N Coleman, Nicole Russell, Oliver Eng, Rebecca A Snyder
Journal: Journal of Clinical Oncology (2025)

682 Background: Participation in pancreatic ductal adenocarcinoma (PDAC) clinical trials remains dismal among patients from minoritized groups. This study aimed to investigate if clinical trial design, including eligibility criteria, affects representation of minoritized populations. Methods: United States Phase I-IV PDAC clinical trials between 2000-2020 were extracted from the ClinicalTrials.gov database. The Surveillance, Epidemiology, and End Results (SEER) database was used to determine cancer incidence linked with years of trial enrollment. Enrollment fraction (EF) was defined as the number of trial participants divided by the incidence of PDAC in each racial and ethnic group. Representation Quotient (RQ) was defined as the proportion of trial participants divided by proportion of PDAC incidence for each subgroup, where underrepresentation was RQ &lt;1.0. Results: 8451 patients from 228 unique PDAC clinical trials were analyzed. 55.7% (n=128) and 44.3% (n=102) trials reported racial and ethnic demographic data, respectively. Non-Hispanic Black (NHB), Non-Hispanic Asian/Pacific Islander (NHAPI), Non-Hispanic American Indian/Alaskan Native (NHAIAN), and Hispanic patients were underrepresented (Table). NHB patients were more likely to be underrepresented in trials for metastatic PDAC disease (89.4% vs. 73.8% of trials, p=0.035). NHB patients demonstrated an increase in median RQ (0.28 vs. 0.48) in trials from 2000-2010 vs. 2011-2020, while Hispanic patients had a decreased median RQ (0.36 vs. 0.25). Trials with renal insufficiency exclusion criteria without cutoffs or explicit methodology were more likely to accrue NHB patients (RQ 0.88 vs. 0.46, p=0.02), whereas trials that used a creatinine cutoff or the modified Cockcroft-Gault (CG) formula did not significantly affect RQ. Other eligibility criteria including cardiac history, HIV, Hepatitis B/C, and receipt of neoadjuvant therapy did not significantly affect RQ for any racial or ethnic group. Trial location and funding source did not affect RQ for any group. Conclusions: Systemic barriers persist in minority enrollment in PDAC clinical trials. Clinical trial design optimizing inclusive eligibility requirements is a first feasible step in increasing minority clinical trial enrollment. Racial and ethnic representation in pancreatic ductal adenocarcinoma clinical trials. Enrollment Fraction (Median, IQR) Representation Quotient (Median, IQR) NHW 0.28 (0.12-0.62) 1.17 (1.09-1.24) NHB 0.15 (0-0.33) 0.47 (0-0.87) NHAPI 0 (0-0.23) 0 (0-0.45) NHAIAN 0 (0-0) 0 (0-0) Hispanic 0.07 (0-0.21) 0.26 (0-0.68) *Abbreviations: Interquartile Range (IQR), Non-Hispanic Black (NHB), Non-Hispanic Asian/Pacific Islander (NHAPI), Non-Hispanic American Indian/Alaskan Native (NHAIAN).
Disparities in outcomes of pancreatic cancer hospitalizations: A ten-year trend study.
Authors: Ayobami Gbenga Olafimihan, Inimfon Nsikak Jackson, Ferdinand Ugwuja, Chiamaka Elsie Nwachukwu, Michael Russell Mullane
Journal: Journal of Clinical Oncology (2025)

683 Background: Pancreatic cancer is the third leading cause of cancer mortality in the United States with 51,750 estimated deaths from Pancreatic cancer in 2024. Demographic variations have been reported with Pancreatic cancer. Our aim was to identify trends in demographic-specific disparities in inpatient pancreatic cancer outcomes. Methods: This is a retrospective longitudinal trends study using the Nationwide Inpatient Sample (NIS) database (2010-2019). We identified hospitalizations with pancreatic cancer using ICD-9 and ICD-10 codes. We highlight disparities in mortality outcomes stratified by age, gender and race. Results: There were 992,550 hospitalizations of pancreatic cancer patients between 2010 and 2019. Over the period, the mean age at hospitalization was similar at 68 years (P = 0.006). A majority of the admissions were elderly patients (≥65 years) identifying as males and Caucasians (P &lt; 0.01). Most patients had Medicare and were in large and urban teaching hospitals (P &lt; 0.001). Over the decade, there was an overall decline in inpatient mortality, from 8.2% in 2010 to 7.1% in 2019 (P trend = 0.004). Amidst the age subgroups, only the elderly patient group experienced a significant decline in mortality rate (8.8% to 7.3%; P trend = 0.004). The young adult population (&lt;45 years) had a trend towards increasing mortality rate, but it was not significant (P trend= 0.139). On gender subgroup analysis, only males had a significant decline in mortality rate (P trend= 0.003). On racial subgroup analysis, only Caucasians had a significant decline in mortality trend (P trend= 0.004) during the study period. Conclusions: There was an overall improvement in the mortality outcome of pancreatic cancer hospitalizations. On sub-group analysis, significant decline in mortality over the decade were seen only in elderly, male and Caucasian patient groups. Targeted research is needed in understanding the root causes of these disparities in pancreatic cancer outcomes and develop effective intervention to bridge this gap. Trends in mortality outcomes of pancreatic cancer hospitalizations by demographic subgroups. Mortality rate, % 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 P- Trend value Overall 8.21 7.94 7.85 7.70 7.73 7.68 7.46 7.87 7.47 7.14 0.004 Young (&lt;45 years) 4.45 5.55 5.23 6.08 6.27 5.32 3.63 6.84 6.95 6.35 0.14 Middle-aged (45- 64 years) 7.55 7.24 7.74 7.32 7.03 6.99 7.62 6.80 6.74 6.91 0.06 Elderly (&gt;65 years) 8.81 8.44 8.04 8.00 8.22 8.19 7.54 8.48 7.87 7.29 0.004 Females 7.72 7.32 7.23 7.15 6.99 7.31 6.72 7.38 7.01 6.87 0.08 Males 8.67 8.57 8.44 8.22 8.44 8.04 8.13 8.32 7.90 7.38 0.003 Whites 7.94 7.49 7.48 7.39 7.81 7.29 6.81 7.39 7.19 6.80 0.004 Blacks 9.87 9.40 9.38 9.15 8.35 8.13 9.40 9.01 8.55 8.41 0.07 Hispanics 7.10 8.99 8.02 6.85 6.66 8.80 7.54 7.43 7.10 6.14 0.05