tbuckley/cabot-search huggingface dataset:
Clinical outcomes of camrelizumab + rivoceranib vs sorafenib (CARES-310) as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC) of non-viral and viral etiology.
Authors: Rachna T. Shroff, Wei Shi, Xiuzhi Wu, Xianzhang Meng, Melissa Maj, Kristin Ryan, Chris Galloway, Laura Alexander
Journal: Journal of Clinical Oncology (2025)

578 Background: CARES-310 (NCT03764293) evaluated the combination of PD-1 inhibitor, camrelizumab (cam), and VEGFR-1-3 inhibitor, rivoceranib (rivo), compared to sorafenib (sor) for the treatment of uHCC. Cam + rivo significantly improved median overall survival (mOS) and median progression-free survival (mPFS) compared to sor (mOS, 23.8 months [mo] [95% CI 20.6, 27.2] vs 15.2 mo [95% CI 13.2, 18.5] hazard ratio [HR] 0.64 [95% CI 0.52, 0.79]; one-sided p&lt;0.0001; mPFS, 5.6 mo [95% CI 5.5, 7.4] vs 3.7 mo [95% CI 3.1, 3.7]; HR 0.54 [95% CI 0.44, 0.67]; one-sided p&lt;0.0001). The most common (≥10%) grade ≥3 treatment-related adverse events in the cam + rivo arm were hypertension (38.6%) and AST increased (20.2%). Methods: A post-hoc analysis of CARES-310 was performed, where mOS and mPFS were estimated using the Kaplan-Meier method and compared between the 3 etiology groups of non-viral, hepatitis C virus (HCV), and hepatitis B virus (HBV) using the log-rank test. Results: mOS was longer with camrelizumab plus rivoceranib compared with sorafenib in patients with non-viral (HR 0.68 [95% CI 0.39, 1.19]), HCV (HR 0.37 [95% CI 0.162, 0.84]), and HBV etiologies (HR 0.70 [95% CI 0.55, 0.89]) (Table). Similarly, mPFS was longer with camrelizumab plus rivoceranib compared with sorafenib in patients with non-viral (HR 0.55 [95% CI 0.34, 0.91]), HCV (HR 0.50 [95% CI 0.23, 1.06]), and HBV etiologies (HR 0.57 [95% CI 0.45, 0.72]) (Table). Conclusions: Cam + rivo in CARES-310 suggested clinically meaningful mOS benefit in non-viral and viral HCC vs sor and provides assurance of clinical benefit for first line treatment to patients with uHCC independent of etiology. Clinical trial information: NCT03764293 . Etiology Group Camrelizumab + Rivoceranib (n=272) Sorafenib(n=271) Non-viral, n (%) 42 (15.4%) 45 (16.6) mOS, mo (95% CI) 26.8 (10.3, NR) 15.2 (9.6, 23.2) mPFS, mo (95% CI) 6.1 (4.1, 13.8) 3.7 (2.4, 5.5) HCV, n (%) 22 (8.1) 29 (10.7) mOS, mo (95% CI) 31.7 (10.8, NR) 13.3 (8.0, 21.5) mPFS, mo (95% CI) 12.7 (3.7, NR) 3.7 (1.8, 9.1) HBV, n (%) 208 (76.5) 197 (72.7) mOS, mo (95% CI) 23.0 (18.9, 26.0) 15.6 (13.3, 19.2) mPFS, mo (95% CI) 5.6 (5.5, 7.3) 3.7 (2.7, 3.7) HCC, hepatocellular carcinoma; mOS, median overall survival; mPFS, median progression-free survival; mo, months; HR, hazard ratio; HCV, hepatitis C virus; HBV, hepatitis B virus, NR, not reached. Results used Cox proportional hazard model. Confidence Intervals (CI) used the Brookmeyer and Crowley method.
Phase I/II study of cabozantinib alone or in combination with panitumumab in patients with <i>MET</i> -amplified metastatic colorectal cancer.
Authors: Saori Mishima, Akihito Kawazoe, Takashi Ohta, Taito Esaki, Takeshi Kato, Eiji Shinozaki, Hiroya Taniguchi, Yoshito Komatsu, Nozomu Fuse, Masashi Wakabayashi, Maiko Takakusa, Seiko Matsuda, Hitomi Tamura, Shogo Nomura, Akihiro Sato, Satoshi Fujii, Yoshiaki Nakamura, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2025)

146 Background: Despite the introduction of anti-EGFR therapies, resistance remains a significant challenge in metastatic colorectal cancer (mCRC). MET amplification is a recognized resistance mechanism. Cabozantinib, a multi-kinase inhibitor targeting MET, has shown promise in overcoming resistance to anti-EGFR therapy. This study aimed to evaluate the efficacy and safety of cabozantinib alone (Cabo) or in combination with panitumumab (Cabo+Pmab) in patients with MET-amplified mCRC. Patients and Methods: The study population included patients with RAS and BRAF wild-type mCRC who had progressed on anti-EGFR therapy and subsequently confirmed MET amplification by circulating tumor DNA. The phase I part aimed to establish the recommended cabozantinib dose in combination with panitumumab by assessing dose-limiting toxicity (DLT) within the first four weeks. The primary endpoint of phase II part was objective response rate (ORR) in patients receiving the study treatment as third-line therapy or later. In phase II part, patients were randomized to Cabo or Cabo+Pmab group. Based on a threshold ORR of 1.6% response rate and an expected efficacy of 30%, the planned sample size was 14 patients with one-sided alpha of 1.25% and power of 80% in each arm, Cabo and Cabo+Pmab. A tumor response of at least 3 out of 14 patients would warrant further investigation of these treatments. Results: A total of 35 patients were enrolled (6 in phase I and 29 in phase II, 28 for the primary analysis; 13 in Cabo and 15 in Cabo+Pmab). In phase I, no DLTs were observed. This allowed researchers to set the maximum tolerated dose and recommend a dosage of 60 mg/day of cabozantinib in combination with panitumumab for phase II. Of 28 pts for the primary analysis, ORR was 7.7% (1/13; 95%CI 0.2-36%) in Cabo group and 0% (0/15; 95%CI 0-21.8%) in Cabo+Pmab group, median progression-free survival was 3.1 months in both groups, and cumulative proportion of pts with grade ≥3 treatment-related adverse events was 38.5% (including hypertension [23.1%]) in Cabo and 60% (including hypomagnesaemia [20%]) in Cabo+Pmab group. Conclusions: The combination of cabozantinib 60 mg plus panitumumab had manageable safety profile. However, this treatment did not demonstrate significant clinical benefit in patients with MET-amplified mCRC. Further investigation is warranted to explore alternative therapeutic strategies for this patient population. Clinical trial information: jRCT1080224637 .
A phase II study of neratinib (Nera) in combination with chemotherapy/trastuzumab/pembrolizumab (C/T/P) in HER2 overexpressing gastroesophageal cancers (GECs).
Authors: Dae Won Kim, Lauren Ponto, Allan Andresson Lima Pereira, Richard D. Kim, Chandler Kracht, Gregory Lauwers, Jose Mario Pimiento, Tiago Biachi de Castria, Jonathan R. Strosberg, Mintallah Haider, Iman Imanirad, Trenton A Avriett, James Costello, Sarah E. Hoffe, Dung-Tsa Chen, Sarbajit Mukherjee, Rutika Mehta
Journal: Journal of Clinical Oncology (2025)

TPS514 Background: Human epidermal growth factor receptor 2 (HER2) is overexpressed in about 15-20% of GECs and is tested using immunohistochemistry and/or in-situ hybridization. Per 3 rd interim analysis of KN-811 study, addition of P to C/T improved overall response rate (ORR) and overall survival (OS) in patients with HER2 positive tumors. HER2 heterogeneity and activation of other signaling pathways ultimately leading to T resistance limits its potential to have a durable response. Nera is an anilinoqiunoline derivative intracellular oral kinase inhibitor that irreversibly binds to epidermal growth factor receptor (EGFR), HER2 and HER4. In this study, we hypothesize that targeting other oncogenic pathways with Nera may help derive additional therapeutic benefit in HER2 positive GECs when combined with C/T/P. Methods: This is an open-label, single arm, multi-institutional Phase II study of Nera in combination with C/T/P in HER2 overexpressing GECs as 1 st line treatment. The first 6 pts as a lead-in phase will be evaluated for toxicity. If no dose limiting toxicity (DLT), a total of 30 patients (include the first 6pts in the lead-in phase) will be used to evaluate efficacy in the phase II portion. All pts will receive standard dose mFOLFOX/trastuzumab q2w along with pembrolizumab 400 mg q6w. Nera will be dosed at 240 mg daily. In case of DLTs observed with this dose, a dose of 160 mg/day for Nera will be considered. Estimated sample size is 30-36 pts using Simon 2 stage design. Primary endpoint in ORR. The null hypothesis will be rejected if 26 or more responses are observed in 30 patients. Key inclusion criteria include: HER2 positive GECs (as determined by local testing), treatment naïve for stage IV disease, measurable disease, ECOG 0-1, preserved cardiac function. Uncontrolled brain metastases or impaired organ function that poses risk with treatment are key exclusion criteria. Primary endpoint is ORR and secondary endpoints include safety, duration of response, clinical benefit rate and OS. The trial is registered on clinicaltrials.gov under NCT06109467. Clinical trial information: NCT06109467 .
Incidence trends of early-onset colorectal cancer (EOCRC) in the United States, by age, sex, race and ethnicity, and urbanicity (2000-2021).
Authors: Erin Van Blarigan, Meg A. McKinley, Laurel J. Finster, Iona Cheng, Scarlett L. Gomez, Robert Haile
Journal: Journal of Clinical Oncology (2025)

26 Background: Research is needed to understand the extent to which the incidence of early onset colorectal cancer (EOCRC)is rising across population sub-groups, including by age, sex, race/ethnicity, and urbanicity, to inform hypotheses regarding its causes and strategies for screening and prevention. Methods: We used data on colorectal cancer cases diagnosed among adults 20-49 years (yr) between 2000-2021 in the delay-adjusted Surveillance, Epidemiology, and End Results (SEER) database (April 2024). We calculated delay- and age-adjusted annual incidence rates (IR) per 100,000, overall and by age, sex, race/ethnicity, and urbanicity. Urbanicity was defined using USDA Rural-Urban Continuum Codes for county; 1-3 were classified as urban and 4-9, 98, and 99 were classified as non-urban. We used NCI’s Joinpoint regression models (Joinpoint version 5.2.0.0) to estimate annual percent change (APC) and 95% confidence intervals (CI). We also calculated IRs for the most recent 5-year period (2017-2021) and used incidence rate ratios (IRR) to compare across groups; IRs and IRRs were calculated using SEER*Stat version 8.4.3. Results: Analyses included 155,500 cases of EOCRC. Most cases (72%) occurred among adults 40-49 yr; 22% occurred among those 30–39 yr and 6% in people 20-29 yr. Among adults 40-49 yr, the incidence of EOCRC increased 4.4% / yr on average between 2018-2021 (95%CI: 2.5, 5.6). Among adults 30-39 yr, incidence of EOCRC increased 3.0% / yr, on average, starting in 2010 (95%CI: 2.4, 4.5). For adults ages 20-29 yr, there were large increases in incidence from 2000-2016 (2000-2013, APC: 3.5; 95%CI: 2.4, 4.1; 2013-2016, APC: 11.2; 95%CI: 6.8, 13.5) but no change from 2016-2021. For the most recent 5-yr period (2017-2021), females had lower IR compared to males (IRR: 0.90; 95%CI: 0.88, 0.91), but trends over time were similar by sex. The incidence of EOCRC increased across races and ethnicities between 2000-2021, albeit at different rates. In the most recent period (2017-2021), the IR per 100,000 was 22.0 for Non-Hispanic American Indian and Alaskan Native (AIAN), 15.0 for Non-Hispanic White, 14.9 for Non-Hispanic Black, 12.4 for Hispanic or Latino, and 11.2 for Non-Hispanic Asian American or Pacific Islander adults. People in non-urban areas had a higher incidence of EOCRC compared to those in urban areas (IRR: 1.18; 95%CI: 1.14, 1.22), with similar trends over time. Conclusions: The incidence of EOCRC is highest among adults 40-49 yr, males, Non-Hispanic AIAN adults, and in non-urban areas. Trend analyses generally showed similar increases in incidence (3-5%/yr) in recent periods across sex, race/ethnicity, and urbanicity.
Adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations and overall mortality among adults with colorectal cancer in a multiethnic cohort study.
Authors: Edgar Asiimwe, Irina Tolstykh, June M. Chan, Stacey A Kenfield, Lynne Wilkens, Loic Le Marchand, Christopher Haiman, Iona Cheng, Erin Van Blarigan
Journal: Journal of Clinical Oncology (2025)

29 Background: High adherence to AICR recommendations on diet, adiposity, and physical activity is associated with improved survival among adults with colorectal cancer (CRC). However, over 80% of participants in existing studies self-reported as non-Hispanic White (NHW). We studied the association between adherence to AICR recommendations and overall mortality among adults with CRC in a multiethnic cohort. Methods: This prospective analysis used data from the Multiethnic Cohort (MEC) study. The MEC is a racially/ ethnically diverse cohort of over 200,000 participants residing in Hawaii and Los Angeles. Lifestyle behaviors in the MEC were assessed by questionnaire at enrolment/Q1 (1993-1996) and periodically over follow-up. We included those with incident CRC before completing Q3 (2003-2008). Follow-up was from Q3 survey completion to December 2019. The main exposure was the standardized AICR score [0-7 points] at Q3. The primary outcome was overall mortality; CRC-specific mortality was secondary. We used multivariable Cox proportional hazards regression to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CIs). Results: There were 1127 adults diagnosed with CRC prior to Q3. Of these, 1079 (95.7%) had non-missing data on the AICR score and comprised our study population. Median (IQR) age at diagnosis was 69 (62-75); median (IQR) follow-up was 12.2 (0.1-16.4) years. There were 489 (45.3%) women. By self-reported race/ethnicity, there were: 153 (14.2%) Black/African Americans, 453 (42.0%) Japanese Americans, 79 (7.3%) Latinos, 165 (15.3%) Native Hawaiians, and 229 (21.2%) NHWs. Only 48 (4.4%) adults had high adherence (AICR≥5 points). Those in the highest category of AICR scores (AICR≥4.5) had statistically significant lower risk of overall mortality relative to those in the lowest category (AICR≤2.5) (HR: 0.64, 95% CI, 0.47-0.89). A similar (but non-statistically significant) association was observed with CRC-specific mortality [HR (high vs low): 0.70, 95% CI, 0.31-1.60]. Those who increased their score between Q1&amp;Q3 had lower overall mortality (HR: 0.87, 95% CI,0.79 - 0.96). Similar trends were observed in stratified analysis by race/ethnicity; however, statistical power was limited. Conclusions: High adherence to AICR recommendations was associated with lower risk of overall mortality in this multiethnic population of adults with CRC. Efforts to increase adherence to AICR recommendations in this population are needed.
A phase II study of agenT-797 (invariant natural killer T-cells), botensilimab (Fc-enhanced CTLA-4 inhibitor) and balstilimab (anti-PD-1) in patients with advanced, refractory gastroesophageal adenocarcinoma.
Authors: Samuel Louis Cytryn, Steven Brad Maron, Yelena Y. Janjigian
Journal: Journal of Clinical Oncology (2025)

TPS515 Background: Esophagogastric (EG) cancer, the fifth most common cancer worldwide and second leading cause of cancer-related mortality, results in 1.3 million deaths annually. Despite recent advances in frontline management, nearly all patients with metastatic disease experience progression, highlighting the urgent need for novel therapies. Botensilimab (BOT), an Fc-enhanced, multifunctional anti-CTLA-4 antibody, has shown promise in combination with balstilimab (BAL, anti-PD-1) across multiple treatment-refractory cancers. Additionally, agenT-797, an allogeneic off-the-shelf invariant Natural Killer T (iNKT) cell therapy, enhances immune responses, including in settings refractory to immune checkpoint inhibitors (ICI), without requiring HLA matching or lymphodepletion. In a cohort of 82 previously treated patients, agenT-797 demonstrated a favorable safety profile with no severe Cytokine Release Syndrome, Graft-versus-Host Disease, or immune effector cell-associated neurotoxicity syndrome. Notably, in patients with relapsed/refractory gastric cancer, agenT-797 plus anti-PD-1 showed important clinical activity that warrants further exploration. Given their complementary mechanisms of action in modulating anti-tumor immunity, we aimed to evaluate the safety and efficacy of combining BOT, BAL, and agenT-797 with standard ramucirumab (anti-vascular endothelial growth factor receptor-2 antibody) and paclitaxel chemotherapy in patients with advanced EG cancer who have progressed on frontline therapy. Methods: This is an investigator-initiated, single-arm phase II trial in adult patients (≥18 years) with esophageal, gastric, or gastro-esophageal junction (GEJ) adenocarcinoma who have received one prior line of therapy, performed at Memorial Sloan Kettering Cancer Center. Eligible patients receive a single infusion of agenT-797 on cycle 1 day 1, BOT 75 mg on day 1 of cycles 1 through 3, BAL 240 mg on days 1 and 15, ramucirumab 8 mg/kg on days 1 and 15, and paclitaxel chemotherapy 80 mg/m 2 on days 1, 8, and 15 of a 28-day cycle. Treatment is continued until disease progression (defined by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), unacceptable toxicity, or withdrawal of consent. The primary endpoint is overall response rate. The secondary endpoints are safety and tolerability, disease control rate, duration of response, progression-free survival, and overall survival. The regimen will be considered worthy of further investigation if at least 15 out of 37 patients achieve an objective response. To date, 12 patients have been enrolled and started on treatment. This trial is registered with ClinicalTrials.gov, NCT06251793. Clinical trial information: NCT06251793 .
Shifting the paradigm: Early identification of colorectal cancer with C the Signs clinical decision support.
Authors: Seema Dadhania, Brian Herrick, Bea Bakshi, Sana Raoof, Tufia C. Haddad, Tushar Patel, Irbaz Bin Riaz, Miles Payling
Journal: Journal of Clinical Oncology (2025)

54 Background: The incidence of colorectal cancer is increasing rapidly, particularly amongst younger people. Despite a screening program being widely available, most patients are diagnosed with cancer through symptomatic presentation. Leveraging electronic medical records (EMRs) through clinical decision support platforms offers potential for identifying high-risk individuals before clinical suspicion develops. This study aims to explore the challenges associated with early colorectal cancer diagnosis and evaluate the effectiveness of the cancer case finding feature of a cancer management platform called C the Signs. Methods: A retrospective analysis was conducted using data from the Mayo Data Platform, comprising records of 894,275 patients, including 7,348 diagnosed with colorectal cancer. C the Signs was employed to identify patients at risk of colorectal cancer based on EMR data. Sensitivity and specificity analyses were performed to assess the platform's performance in identifying high-risk patients. Additionally, the study evaluated the temporal discrepancy in colorectal cancer diagnoses between those flagged by C the Signs and those detected by primary care physicians. Results: The C the Signs screening platform had a sensitivity of 93.8% and a specificity of 19.7% in identifying patients at risk of colorectal cancer. Notably, 29.4% of patients with colorectal cancer were identified as being at risk up to 5 years earlier by C the Signs compared to diagnoses made by primary care physicians, highlighting the platform's potential for early detection. Conclusions: Early identification of high-risk individuals holds promise for improving patient outcomes and reducing the burden of colorectal cancer. Whilst the specificity of the C the Signs platform for colorectal cancer is relatively low, the sensitivity is comparable to the most favorable rates reported for colonoscopy. In addition, if C the Signs was used in conjunction with a relatively cheap screening test such as Faecal Immunochemical Testing, this would significantly drive up the specificity whilst maintaining the sensitivity. Further studies are needed to assess its efficacy in conjunction with tests available in primary care.
Assessment of clinical value and barriers to use of new investigational targeted agents in the community setting: A study of claudin 18.2 and zolbetuximab.
Authors: Griffin M Wright, Gerald Stanvitch, Maryam Salehi, Isabella Manigault, Eugene Vissers
Journal: Journal of Clinical Oncology (2025)

500 Background: Rapid integration of novel agents in clinical practice can be lifesaving. However, community-based practices may experience extended adoption times, due to practical barriers. REFLECT was developed to assess new drug implementation in the community setting. Methods: REFLECT consists of a 20-minute prerecorded presentation, followed by a data-collection event for community oncologists. It was developed to evaluate and assess challenges of implementing novel targeted agents in the community practice setting. In this pilot study, awareness of zolbetuximab (zolbe), a potential first-in-class claudin 18.2 (CLDN18.2) monoclonal antibody and companion diagnostic, was assessed. Between April and August 2024, 53 data-collection events were held representing 26 states across the US. Data from 492 oncologists were recorded and analyzed. Results: Nearly half the community oncologists (47%) were not familiar with CLDN18.2 as a therapeutic target in gastric/gastroesophageal junction (G/GEJ) cancer. Awareness of zolbe data was low among community oncologists; 79% indicated they had not seen the results from the phase 3 studies. However, 96% of oncologists reported the data will at least moderately impact their treatment of CLDN18.2+ patients with metastatic (m)G/GEJ cancer. Only 40% of oncologists reported having access to CLDN18.2 testing. Uncertainty regarding availability of CLDN18.2 testing was high among oncologists in the Central US (52%), representing a significant awareness gap for CLDN18.2 testing. Opinions were divided regarding the treatment approach for CLDN18.2+, immunosensitive patients (Table). In a HER2–, CLDN18.2+ patient with mG/GEJ cancer and a combined positive score (CPS) of 10; 58.1% would recommend first-line chemotherapy (chemo) plus immunotherapy (IO) and 40.4% would recommend chemo plus zolbe. Conclusions: First-in-class targeted agents often encounter additional challenges and knowledge gaps regarding adoption in the community practice setting, particularly associated with molecular testing. Timely education on patient identification and correct utilization may accelerate adoption of new regimens, and potentially save lives. Data-sharing and -collection platforms including REFLECT can be instrumental in the identification of challenges associated with widespread and rapid implementation of novel agents in the community oncology setting. What treatment approach would you recommend in a patient with the following characteristics, if all treatments were available? mGEJ adenocarcinoma, HER2– disease, CLDN18.2+ staining in &gt;75% of tumor cells, CPS 10. Treatment Total: N = 492% (n) Chemo mFOLFOX6 1.0 (5) CAPOX 0 (0) Chemo + IO mFOLFOX6 + IO 52.8 (260) CAPOX + IO 5.3 (26) Chemo + zolbe mFOLFOX6 + zolbe 33.9 (167) CAPOX + zolbe 6.5 (32) Other 0.4 (2)