tbuckley/cabot-search huggingface dataset:
Preliminary phase 1/1b dose expansion results of the bifunctional EGFR/TGFβ inhibitor ficerafusp alfa (BCA101) with pembrolizumab in patients with squamous cell carcinoma of the anal canal.
Authors: Van K. Morris, Brandon Huffman, Cathy Eng, Rita P. Dalal, Rachel Salazar, David Bohr, Kaitlin H. Morton, Philippe Bedard
Journal: Journal of Clinical Oncology (2025)

4 Background: Anti-PD-1 monotherapy has limited efficacy in patients (pts) with advanced squamous cell cancer of the anal canal (SCAC). In KN-158, pembrolizumab (P) was reported to have an ORR of 10%, DCR of 25%, and a 12-month PFS rate of 15% in patients with incurable SCAC. TGFβ promotes immunosuppression within the tumor microenvironment, and inhibition of this pathway may improve tumor susceptibility to immune checkpoint blockade.Ficerafusp alfa (F)is a bifunctional EGFR/TGFβ inhibitor with manageable safety and favorable preliminary anti-tumor efficacy in advanced solid tumors (ESMO 2022 731MO). We evaluated the combination of F+P in pts with chemotherapy-refractory locally advanced/unresectable or metastatic SCAC. Methods: This single-arm, multicenter dose expansion from an ongoing phase I/Ib trial enrolled pts with ICI-naïve SCAC that was locally advanced/unresectable or metastatic, who had received 1-2 prior lines of chemotherapy. Pts received ficerafusp alfa (1500 mg IV on days 1, 8, 15) and pembrolizumab (200 mg IV on day 1) every 21-day cycle. The primary endpoint was safety (CTCAE v5), and secondary endpoints were radiographic response (RECIST 1.1), duration of response, progression-free survival, and overall survival. Results: Among 26 pts treated, 21 (81%) were female, and median age was 61 (range: 43-82). As of 7/2024, 22 pts are evaluable for efficacy. ORR was 32% (95% CI 13.9-54.9%). Six of the seven responses were confirmed, including one pt with a radiographic PR with pathologic CR to F+P. Seven pts (32%) achieved SD as best response, resulting in DCR of 64%. Median PFS was 2.8 months (95% CI 1.4-14.8) and the PFS rate at 12 months was 36%. G3 treatment-related adverse events were observed in 10/26 pts (38%, most common: Anemia (19%) and acneiform rash (12%)). TRAEs led to permanent discontinuation of study treatment in 2 pts (8%). The most common TRAEs of any grade were acneiform rash (13/26, 50%), epistaxis (46%) and headache (38%). Conclusions: The addition of ficerafusp alfa demonstrated encouraging efficacy, with increased ORR, DCR, and 12-month PFS relative to historical precedent with pembrolizumab alone. Safety and tolerability were acceptable. Further investigation of this combination in pts with advanced SCAC is warranted. Updated data will be presented. Study funded by Bicara Therapeutics Inc. with access to pembrolizumab in collaboration with Merck Sharp &amp; Dohme LLC, a subsidiary of Merck &amp; Co., Inc., Rahway, NJ, USA (NCT04429542). Clinical trial information: NCT04429542 .
Outcomes of neoadjvuant chemotherapy versus chemoradiation for esophageal adenocarcinoma: A National Cancer Database analysis.
Authors: Ravi Shridhar, Kenneth Lee Meredith, Jamie Huston
Journal: Journal of Clinical Oncology (2025)

416 Background: While neoadjuvant chemoradiation (NCRT) has been the acceptable standard of care for esophageal adenocarcinoma (EAC), there has been a paradigm shift from recent trials have shown that neoadjuvant chemotherapy (NAC) is either equivalent or superior to NCRT. We sought to examine the outcomes of NAC versus NCRT in esophageal cancer from the National Cancer Database (NCDB). Methods: Utilizing the NCDB, we identified esophagectomy patients with EAC who underwent multiagent NCT versus multiagent NCRT. Overall Survival (OS) was analyzed with the Kaplan-Meier method and multivariate analysis (MVA) was performed to identify predictors of OS. Propensity score matching (PSM) was used to correct for baseline differences between groups. Results: After PSM, we identified 1007 patients in each group. Groups were equally balanced in age, gender, T/N stage, grade, and facility volume. There was improved lymphadenectomy and higher use of adjuvant therapy in NCT patients. There were significant improvements in R0 resection and pathologic response associated with NCRT patients. There was a significant improvement in OS in NCT versus NCRT. The median and 5-year OS was 42.7 months and 42% in NCT patients versus 34.2 months and 35% in NCRT patients (p = 0.001). For pathologic complete responders, median and 5-year OS was 101 months and 64% in NCT patients versus 71.2 months and 53% in NCRT patients (p = 0.04). On MVA, improved mortality was associated with female gender, pathologic N0, &gt;10 nodes removed, pathologic partial or complete response, R0, well/moderate grade, NCT, adjuvant chemotherapy, and higher facility volume. There was also no survival benefit to adjuvant chemoradiation. Conclusions: Despite higher R0 and pathologic response associated with NCRT, NCT was superior to NCRT for OS in EAC patients. NCRT needs to be re-examined in its role as a treatment recommendation for operable EAC patients. Multivariate analysis for overall survival. Variable HR 95% CI P value Age 1.01 1.00 – 1.02 0.004 SexMaleFemale Reference0.79 0.64 – 0.98 0.03 Charlson Deyo score01 Reference1.05 0.91 – 1.21 0.54 Pathologic N-stageN0N+ Reference1.82 1.58 – 2.10 &lt;0.001 LN removed&lt;10&gt;10 Reference0.81 0.68 – 0.97 0.02 ResponseNonePartialComplete Reference0.810.61 0.69 – 0.940.50 – 0.75 0.008&lt;0.001 Margin statusR0R1 Reference1.24 1.01 – 1.52 0.04 GradeWell/moderatePoor Reference1.35 1.18 – 1.54 &lt;0.001 Preop radiationYesNo Reference0.77 0.67 – 0.88 &lt;0.001 Adjuvant therapyNoneChemotherapyChemoradiation Reference0.770.83 0.65 – 0.920.64 – 1.08 0.0040.17 Facility volumeLow (≤10/year)Medium (11-19/year)High (≥20/year) Reference0.860.78 0.72 – 1.030.67 – 0.90 0.10&lt;0.001
Sex differences in the colorectal tumor immune microenvironment.
Authors: Elizabeth Seitz, Ya-Yu Tsai, Marilena Melas, Sidney S. Lindsey, Christopher P Walker, Joseph D. Bonner, Kevin McDonnell, Gregory Idos, Joel K Greenson, Gad Rennert, Victor Moreno, Stephen B. Gruber, Stephanie Schmit
Journal: Journal of Clinical Oncology (2025)

283 Background: Males have increased risk and mortality rates of colorectal cancer (CRC) compared to females, but the reasons for these disparities are not well understood. Immune responses differ by sex, and a robust T cell response is an important prognostic indicator in CRC. We hypothesized that females exhibit a stronger CRC-associated T cell response, contributing to reduced mortality in females compared to males. Methods: The study cohort included 2,751 incident CRC patients (1,337 female; 1,414 male) from a population-based case-control study. T cell receptor (TCR) abundance and clonality were quantified using immunoSEQ, and a gastrointestinal pathologist scored tumor-infiltrating lymphocyte counts per high-powered field (TILs/hpf). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between T cell metrics and sex, adjusting for age, anatomic site, and microsatellite instability (MSI) status. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals for the association between sex and 5-year all-cause and CRC-specific survival, adjusting for known prognostic indicators. We also conducted a formal test for interaction between sex and T cell features in relation to survival outcomes. Results: There were no associations between sex and TCR abundance (OR=1.05, 95% CI=0.98-1.13, p=0.14), TCR clonality (OR=0.99, 95% CI=0.91-1.06, p=0.72), or TILs/hpf (OR=1.05, 95% CI=0.88-1.25, p=0.60). We observed no differences in overall or disease-specific five-year survival between males and females. Further, the associations between T cell responses and survival did not significantly differ by sex. Conclusions: In a well-powered analysis, no robust sex differences were observed in the CRC immune microenvironment or in the relationship between T cell infiltration and CRC outcomes. The high burden of CRC and the emergence of immunotherapy as an important therapeutic approach suggest a need for further research investigating immunological sex differences in the setting of treatment response. Summary of associations between the colorectal tumor T cell response and sex. T cell Features Odds Ratio(Female vs. Male) Lower 95% CI Upper 95% CI P Value TCR Abundance 1.05 0.98 1.13 0.14 TCR Clonality 0.99 0.91 1.06 0.72 TILs/hpf* &lt;2 1.05 0.88 1.25 0.60 *A total of 99 patients (45 female; 54 male) with missing TILs/hpf data were excluded from the regression analysis.
Oncomine panel testing in the clinical management of colorectal cancer: An Irish experience.
Authors: Mary O Reilly, Bruce Moran, Kieran Sheahan, Des C Winter, Walter Kolch, Fergus Keane, Raymond S. McDermott, Aleksandar Krstic
Journal: Journal of Clinical Oncology (2025)

212 Background: Early onset colorectal cancer (EOCRC) is defined as colorectal cancer (CRC) in those under the age of 50. It has been hypothesized that the molecular signatures of EOCRC could differ from those of late onset CRC (LOCRC). Next Generation Sequencing (NGS) using the Oncomine Precision Assay is a useful tool to guide treatment decisions based on the presence or absence of oncogene drivers. While not all of these mutations currently influence the clinical management of CRC patients, ongoing research on the function of these genes and the development of new drugs could offer insights into patient prognosis, treatment choices and prediction of therapy resistance. Methods: Of &gt;1500 CRC identified between 2010 and 2024, we investigated the clinical and genetic characteristics of 38 EOCRC and 41 LOCRC cases. All cases were microsatellite stable and staged I-III. NGS was performed with the Ion Torrent Genexus integrated platform using the Oncomine 45-gene Precision Assay panel. DNA hotspot mutations and copy number variations (CNVs) were assessed, followed by the classification of clinically relevant mutations using the genetic variant OncoKB database. Results: There were 38 EOCRC and 41 LOCRC cases. The age range was 27 to 49 and 50 to 91, with median ages of 44 and 72, in the EOCRC and LOCRC groups, respectively. Based on the stratification of NGS mutation levels as per the OncoKB classification, all patients in both groups (100%) had level 1 actionable mutations. NRAS wild type (WT) status was present in 100% of patients in both groups. However, differences were observed in KRAS status: 84% (32/38) of EOCRC were KRAS WT, while only 65% (27/41) of LOCRC were KRAS WT. While 3 % (n=1) of the EOCRC cohort had an ERBB2 amplification, none were detected in the LOCRC group. BRAF V600E mutations were present in 11% (4/38) of EOCRC and 12% (5/41) of LOCRC. Level 4 mutations were detected in 18% (n=7) of EOCRC, all of which were PIK3CA mutations, while these were seen in 24% (n=10) of the LOCRC group, including 9 PIK3CA mutations and 1 FGFR1 mutation. Regarding concurrent mutations, 2 patients in the EOCRC group had two mutations each: one with concurrent KRAS and PIK3CA mutations, and another with concurrent JAK2 and KRAS mutations. The LOCRC group had a higher incidence of concurrent mutations, with 8 patients affected: 6 had concurrent KRAS and PIK3CA mutations, and 2 had concurrent BRAF and PIK3CA mutations. Conclusions: Our study demonstrates that EOCRC have higher KRAS WT status and fewer concurrent mutations compared to LOCRC, who exhibit more frequent KRAS non-G12C oncogenic mutations. It also underscores the importance of routine NGS mutation panel analysis in CRC management. Additionally, identifying specific mutations in patients that relapse can guide targeted therapies, potentially improving outcomes and offering personalized treatment options.
Long-term survival outcomes of atezolizumab plus bevacizumab treatment in patients with advanced hepatocellular carcinoma.
Authors: Ching-Tso Chen, Yin-Hsun Feng, Chia-Jui Yen, San-Chi Chen, Chih-Hung Hsu, Yu-Yun Shao
Journal: Journal of Clinical Oncology (2025)

600 Background: Immunotherapy combinations such as atezolizumab plus bevacizumab (Atezo-Bev) or STRIDE have been established as standard therapies for patients with advanced hepatocellular carcinoma (HCC). After dual immunotherapy treatment, durable responders and long-term survivors had been reported. However, the longevity of such outcomes following Atezo-Bev treatment remains to be evaluated. Methods: We analyzed medical records of four medical centers in Taiwan for patients with Child-Pugh class A liver reserve who received first-line Atezo-Bev treatment for advanced HCC from January 2018 to May 2021, to evaluate their survival outcomes after a long-term follow-up. Results: We enrolled 54 patients, predominantly male (90.7%) with the median age of 65 years. The main hepatitis etiology was viral hepatitis (92.6%), including 68.5% chronic hepatitis B. After a median follow-up of 61.9 months, the median overall survival (OS) was 21.0 months (95% confidence interval 10.4 – 31.6 months). The 3-year, 4-year and 5-year OS rate was 36.4%, 25.7% and 25.7%, respectively. For patients with tumor response (N = 19, 34.5%) or disease control (N = 44, 80.0%), the 3-year, 4-year, and 5-year OS rates are listed at Table 1. In univariate analysis, younger age (≤ 70 years), absence of intrahepatic tumor, lack of macrovascular invasion (MVI), and ALBI grade 1 were associated with an OS &gt; 3 years. In multivariate analysis, after adjusting sex, viral hepatitis, MVI, extrahepatic spread, and initial alpha-fetoprotein &gt; 400 ng/ml, the absence of intrahepatic tumor (Odds ratio [OR] = 5.36, p = 0.047) and ALBI grade 1 (vs grade 2, OR = 10.02, p = 0.037) remained independent predictors for OS &gt; 3 years. Conclusions: In patients with advanced HCC, Atezo-Bev treatment led to a notable proportion achieving long-term survival, especially in patients with good response to the treatment. Absence of intrahepatic tumors and preserved liver function are predictive of prolonged survival. 3-year, 4-year and 5-year OS rate of patients who receive Atezo-Bev treatment, stratified by treatment response. Landmark survival OS rate (%) by treatment response Disease control Responder 3 years 35.6 52.2 4 years 30.3 52.2 5 years 30.3 47.7 Responder: patients who achieved a best response of complete response or partial response after treatment with Atezo-Bev. Disease control: includes responders and patients who achieved a best response of stable disease following Atezo-Bev treatment.
Concordance between PD-L1 assays 28-8 and SP263 and their respective scoring algorithms in procured upper gastrointestinal adenocarcinoma samples.
Authors: Thinh Pham, Yihua Liu, Michael Sharpnack, Jenifer Lum, Daniel O. Koralek, Meghna Das Thakur
Journal: Journal of Clinical Oncology (2025)

479 Background: PD-L1 is being studied as a predictive immunohistochemical (IHC) biomarker for gastroesophageal junction (GEJ), gastric (GC), and esophageal (EAC) adenocarcinomas, and anti-PD-(L)1 therapies are used to treat them. Here, we compare the VENTANA PD-L1 (SP263) IHC assay and its tumor area positivity (TAP) algorithm with the clinically validated Agilent PD-L1 IHC 28-8 pharmDX combined positive score (CPS) algorithm in GEJ, GC, and EAC samples. The degree of concordance between SP263 TAP ≥ 5% and 28-8 CPS ≥ 5 is important for interpreting real-world settings and emerging clinical trial data. Methods: GEJ, GC, and EAC tumor samples procured from company-sponsored clinical trials (NCT02545504, NCT02862535, NCT02864381) and external vendors with informed consent were analyzed 4 ways: SP263 TAP, SP263 CPS, 28-8 TAP, and 28-8 CPS. Readouts were evaluated by a single pathologist and were analyzed with Pearson correlation coefficients. Results: 286 patient samples were analyzed (GEJ, n = 106; GC, n = 88; EAC, n = 92). The agreement among the SP263 TAP ≥ 5% and 28-8 CPS ≥ 5 prevalence is shown in the Table. The overall correlation coefficient between 28-8 CPS and SP263 TAP was high ( R = 0.95; P &lt; 2.2 × 10 −16 ). In addition, when applying the same scoring algorithm to both assays (SP263 TAP vs 28-8 TAP or SP263 CPS vs 28-8 CPS), the correlation coefficients remained high ( R = 0.97; P &lt; 2.2 × 10 −16 ). When both algorithms were applied to the same IHC assay (SP263 TAP vs SP263 CPS or 28-8 TAP vs 28-8 CPS), the correlation coefficients were also high ( R = 0.98; P &lt; 2.2 × 10 −16 ). Conclusions: In this controlled experiment the PD-L1 assays 28-8 and SP263 concordance was high. The scoring algorithms for GEJ, GC, and EAC samples were observed as highly correlated; minor differences were likely driven by the distinct PD-L1 monoclonal antibody clones utilized in the IHC assays. These data suggest that the 2 assays are comparable for evaluating PD-L1 expression at the TAP ≥ 5% and CPS ≥ 5 cutoffs. Clinical trial information: NCT02545504 , NCT02862535 , NCT02864381 . Concordance of SP263 TAP ≥ 5% with 28-8 CPS ≥ 5. Positive percentage agreement: 0.96Negative percentage agreement: 0.95Overall percentage agreement: 0.95 28-8 CPS ≥ 5: Positive 28-8 CPS ≥ 5: Negative SP263 TAP ≥ 5%: Positive 116 9 SP263 TAP ≥ 5%: Negative 5 156
AGX101: A TM4SF1-directed tubulin inhibitor conjugate in ongoing first-in-human trial including GI cancers.
Authors: Paul Jaminet, Ildefonso I Rodriguez Rivera, Shou-Ching Jaminet, Glen J. Weiss, Meredith Pelster
Journal: Journal of Clinical Oncology (2025)

829 Background: TM4SF1 (Transmembrane-4 L-Six-Family-Member-1) is an endothelial marker with critical roles in angiogenesis, as well as a tumor cell antigen that contributes significantly to invasion and metastasis. TM4SF1 is upregulated 20-fold in angiogenic tumor vascular endothelium compared to normal vasculature endothelium and exhibits a unique nuclear internalization pathway. AGX101 is a novel tubulin inhibitor conjugate specifically directed against TM4SF1, delivering a potent maytansinoid payload directly to the nucleus of cells within the tumor microenvironment. Delivery to both the vascular and tumor cell compartments of the tumor results in three mechanisms of action (MoAs): (1) activation of tumor immune surveillance, (2) tumor blood supply deprivation, and (3) direct tumor cell killing. Methods: TM4SF1 expression was assessed using immunohistochemistry. Safety and pharmacokinetics of AGX101 were evaluated in non-human primates (NHP), with escalating doses to determine the highest non-severely toxic dose (HNSTD). Efficacy studies were also conducted in mouse models, enabling assessment of the minimum effective dose (MED) needed to engage each of the three MoAs. The combination of HNSTD and MED enables calculation of a therapeutic index (TI). The potential for synergy with immune checkpoint inhibitors (ICIs) was also investigated. A first-in-human study of AGX101 in patients with advanced solid tumors with the primary objective of safety and dose-limiting toxicities (DLTs) has initiated. Results: Notable cancers with high TM4SF1 scoring intensity include pancreatic adenocarcinoma, hepatocellular carcinoma, cholangiocarcinoma, and gastric cancer. In esophageal cancer, 20% of patients have a TM4SF1 copy number amplification, and these have worse prognosis. In NHP, AGX101 exhibited a favorable safety profile. In preclinical efficacy studies, monotherapy demonstrated robust efficacy through each of the three MoAs in syngeneic models in mice including CT26 colon carcinoma, and human tumor xenograft models including MIA PaCa-2 pancreatic cancer. Measured by exposure, TI was large. In syngeneic mouse models including CT26, the effects of ICIs were potentiated, suggesting a potential synergistic approach in cancer therapy. The first two dose levels of AGX101 monotherapy in humans has cleared without DLTs. Three patients with pancreatic adenocarcinoma have been treated thus far. Conclusions: AGX101, targeting the TM4SF1 antigen, represents a promising new approach in cancer therapy. The preclinical data suggest that AGX101 could provide a significant therapeutic benefit by novel and differentiated mechanisms of action, namely selectively targeting the tumor vasculature and potentiating immune-based therapies. Further clinical development of AGX101 is ongoing and initial outcome data will become available by the conference. Clinical trial information: NCT06440005 .
Neoadjuvant chemotherapy with FOLFOXIRI for high-risk relapsed locally advanced colon cancer: A single-arm phase II trial.
Authors: Yuwen Zhou, Wenjian Meng, Meng Qiu
Journal: Journal of Clinical Oncology (2025)

201 Background: To evaluate the safety and efficacy of neoadjuvant chemotherapy (NAC) with three drug-intensity chemotherapy (oxaliplatin, irinotecan, and fluorouracil [FOLFOXIRI]) in patients with high-risk factors for recurrence and metastasis of locally advanced colon cancer (hr-LACC). Methods: A single-arm, open-label, phase II trial was conducted at West China Hospital of Sichuan University from July 2020 to Oct 2023. Patients with T4a/b or (and) N2/fused lymph nodes) and no distant metastases were considered as the hr-LACC patients. Eligible enrolled patients received four cycles of NAC with FOLFOXIRI followed by surgery and adjuvant chemotherapy with capecitabine and oxaliplatin (CAPOX) for two to five cycles or single-agent capecitabine for five cycles or observation. The primary endpoint was the rate of TRG grade 0-2 according to the criteria of NCCN guideline. Results: Of 72 patients enrolled (median age 53 [18-74] years,65 were T4a/b [90.2%], 66 were N2 [91.6%]), 58 patients (80.6%) completed four cycles of FOLFOXIRI. Three patients (4.2%) achieved clinical complete response. Twenty-eight patients (39.4%) obtained clinical partial response. The most common adverse event (AE) was nausea (86.1%, 62/72); grade 3-4 AEs occurred in 37 of 72 patients (51.4%).R0 resection was achieved in 64 of 64 patients, and the TRG (0-2) rate was 87.5% (56/64). The pathologic complete response rate was 7.8% (5/64). The proportions of pT0-2 and pN0 were 21.9% and 68.8%, respectively. Only three (4.7%) patients had prolonged hospital stay due to perioperative complications. No patient died within 30 days and 90 days after surgery. The 2-year tumor recurrence rate was 17.2%. Conclusions: For patients with hr-LACC, NAC with FOLFOXIRI regimen was safe and effective. Longer follow-up and larger clinical studies are needed to validate this innovative regimen. Clinical trial information: NCT05018182 .