tbuckley/cabot-search huggingface dataset:
BXQ-350, a novel sphingolipid metabolism modulator, in combination with mFOLFOX7 and bevacizumab in newly diagnosed metastatic colorectal cancer (mCRC) patients: A phase 1b/2 randomized study.
Authors: Daniel Blake Flora, Reema Anil Patel, Fa-Chyi Lee, Gilles Tapolsky, Ray Takigiku, Jim Beach, Michael Gazda, Tariq Arshad
Journal: Journal of Clinical Oncology (2025)

TPS320 Background: Ceramides and sphingosine-1-phosphate (S1P) are key bioactive signaling molecules. Ceramides are proapoptotic and mitigate chemoresistance. Conversely, S1P promotes cancer cell proliferation, activates multiple oncogenic pathways, and stimulates immuno-suppressor cell populations promoting a pro-tumoral microenvironment. Several studies in colorectal cancer patients have shown high levels of ceramides are associated with improved survival, while high S1P levels are associated with a poor prognosis. Hence, modulation of sphingolipid metabolism could be a promising therapeutic approach. BXQ-350 is a nanovesicle of Saposin C, an allosteric activator of sphingolipid metabolism, that lowers systemic S1P and increases C18 ceramide. BXQ-350 was investigated in a Phase 1 dose-escalation safety study in cancer patients with advanced solid malignancies (NCT02859857). BXQ-350 was safe and well-tolerated (no DLT, no MTD). Also, 13 patients (~17.8% of evaluable patients) had a clinical benefit up to cycle 6 and beyond (PR, SD). Among patients with PFS &gt; 6 months, there were 4 recurrent CRC patients: 1 patient had a PFS of ~12 months, 2 of ~18 months, and 1 is still on study after 7 years suggesting potential long-term benefit. Furthermore, there were signs that BXQ-350 may alleviate symptoms of CIPN as 4 out of 10 patients with chronic CIPN at time of enrollment experienced an improvement of their symptoms. Methods: BXQ-350 is being investigated in a Phase 1b/2 study in combination with mFOLFOX7 and Bevacizumab in newly diagnosed mCRC patients (NCT05322590) to assess the efficacy and safety of BXQ-350. Design of the Phase 1b (open label study): 1) A safety dose escalation part to establish the RP2D: patients will initially receive 1.8 mg/kg BXQ-350 in combination with mFOLFOX7 and Bevacizumab. If safe (no MTD), dose of BXQ-350 will be increased to 2.4 mg/kg and 9 additional patients will be entered at this dose level. If safe, then this dose will be the RP2D and 21 additional patients will be enrolled, completing a 30 patient expansion cohort 2) Efficacy will then be evaluated for all patients entered at the RP2D. Primary objectives of the Phase 1b are to assess safety, identify RP2D, and assess preliminary efficacy of BXQ-350 in this combination. A secondary objective is to determine if BXQ-350 decreases CIPN. Enrollment in the expansion cohort of 30 patients is nearly complete, with 26 patients enrolled as of September 2024. Clinical trial information: NCT05322590 .
Gender and ethnic disparities in hepatocellular carcinoma: Trends in incidence rates across U.S. populations from 2000 to 2021.
Authors: Lauren Guerrero Negrón, Michael Buckstein, Mhango Grace
Journal: Journal of Clinical Oncology (2025)

524 Background: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver strongly associated with liver cirrhosis and the etiologies producing cirrhosis. As such, racial and ethnic factors might affect incidence rates of HCC resulting in disparities. While disparities have been reported, the effect of gender within certain populations, particularly Hispanic and non-Hispanic White ancestry, have not been fully explored. This study looks at the changing incidence rates of HCC in the US amongst different populations with a particular focus on the impact of gender on incidence. Methods: Incidence rates of HCC between 2000 and 2021 among different sexes within racial and ethnic groups in the United States were analyzed utilizing delay-adjusted data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Annual percent change (APC) was calculated by using Joinpoint Regression software. Results: Overall, HCC incidence rates since 2014 to 2021 show a slight decrease (APC, -0.06). While Hispanic men HCC incidence rates declined from 2012 to 2021 (APC, -0.44), Hispanic women incidence have had a steady increase since 2000 (APC, +2.52). Non-Hispanic Black men (APC, -3.07) rates vastly declined from 2015 to 2021 while non-Hispanic black women interestingly experienced a slight decrease in incidence from 2013 to 2021 (APC, -0.34). Non-Hispanic White men experienced stagnant rates of HCC since 2014 (APC, -0.05) while non-hispanic white women (APC, +3.59) showed increasing trends in HCC incidence since 2003. For comparison, non-Hispanic Asian/Pacific Islander men (APC, -2.19) and women (APC, -2.36), which both experienced a decline since 2007. This analysis was repeated without significant change. Further corroborations are necessary to validate these findings. Conclusions: These findings show that while the incidence rates of HCC overall have decreased, this benefit appears to be largely driven in male populations. In contrast, in women, and particularly Hispanic and Non-Hispanic White women, incidence rates have been increasing. This phenomenon likely reflects the changes in etiologies of cirrhosis and HCC. Surveillance strategies and screening might need to be optimized to reflect these trends.
Trial in progress for a colorectal cancer detection blood test.
Authors: Sarah Sawyer, Sascha Ellers, Mary Shravanthi Kakumanu, Bhavana Bommireddy, Marjan Pasgar, Dione Susan-Kurian, Marianne T Santaguida, Shifra Krinshpun, Alexey Aleshin, Bree Mitchell, Adham A Jurdi
Journal: Journal of Clinical Oncology (2025)

TPS306 Background: Blood-based biomarkers for cancer screening have garnered much anticipation in recent years. Current colorectal cancer screening methodologies such as colonoscopy and stool-based tests are plagued with low compliance rates. While scientific advancement calls for clinical trial recruitment from diverse backgrounds to ensure health equity, traditional clinical trial design has led to the underrepresentation of such populations, resulting in a gap in our understanding of disease conditions, preventative measures, and appropriate treatment across populations. Here, we describe an ongoing, decentralized, prospective sample collection clinical study, PROCEED-CRC, to develop a blood-based CRC screening test in an average-risk population. Methods: The primary endpoint of the study is to achieve the successful enrollment of up to 1500 evaluable patients. Key eligibility criteria include participants aged ≥40 years, planning to undergo an asymptomatic screening colonoscopy, willing to provide a blood sample within 120 days prior to a colonoscopy procedure, and an informed consent prior to participation in the study. Exclusion criteria include individuals who have had a prior malignancy, have undergone diagnostic colonoscopy in the past 9 years, or any other recent CRC screening tests, precancerous findings on recent colonoscopy, or are at high risk for CRC based on germline carrier status. Primary analysis would include summarizing the number and percentage of participants classified to have CRC, advanced adenoma, or non-advanced neoplasia. In order to reach a diverse study cohort that is representative of this average-risk US population aged over 45 years, we implemented several non-traditional recruitment outreach efforts, such as engaging a pharmacy provider to whom individuals may have previously consented to receive messages/notifications. Additional outreach efforts include digital advertisements and referral letters from healthcare professionals and community advocacy groups. Through these efforts, interested participants will have access to a link, a web address, or QR code to be screened for the study. After informed consent and enrollment, participants may schedule a blood draw via a mobile phlebotomy center based on their availability. Participants are considered evaluable if they meet the inclusion criteria, provide informed consent, provide an adequate blood draw, complete the screening colonoscopy within 120 days of the blood draw, and have medical records and pathology reports provided. The data from this study is expected to be completed in May 2025.
A multicenter, phase 2 study of atezolizumab plus bevacizumab (atezo+bev) combination therapy in patients with unresectable hepatocellular carcinoma (HCC) and Child–Pugh class B cirrhosis: CHALLENGE trial final results.
Authors: Masafumi Ikeda, Takeshi Terashima, Tatsuya Yamashita, Takuji Okusaka, Hiroshi Imaoka, Tomokazu Kawaoka, Satoshi Kobayashi, Sadahisa Ogasawara, Atsushi Hiraoka, Masahito Nakano, Fumio Nagashima, Rie Sugimoto, Michihisa Moriguchi, Yoshitaka Inaba, Satoru Shinoda, Makoto Ueno, Naoya Kato, Masatoshi Kudo, Junji Furuse, Hiroaki Nagano
Journal: Journal of Clinical Oncology (2025)

587 Background: The Phase 2 CHALLENGE trial (jRCTs031210355) evaluated the safety and efficacy of atezo+bev combination therapy in patients with advanced HCC with Child–Pugh class B cirrhosis. Results of the trial’s main analysis demonstrated that atezo+bev was well-tolerated. Here, we present the trial’s final safety and efficacy outcomes. Methods: This multicenter, open-label, single-arm, Phase 2 study enrolled patients with advanced HCC and a Child–Pugh score of 7 or 8 who had not received prior systemic therapy. Patients were administered atezolizumab 1200 mg plus bevacizumab 15 mg/kg every 3 weeks. The primary endpoint was the frequency of severe adverse events (SAEs). Secondary endpoints included the objective response rate (ORR), progression-free survival (PFS), time to progression (TTP), overall survival (OS), and frequency of adverse events (AEs). Results: A total of 31 patients were enrolled between December 2021 and April 2023. Child–Pugh score was 7 points in 25 patients (80.6%) and 8 points in 6 patients (19.4%). Fourteen patients (45.2%) were classified as having Barcelona Clinic Liver Cancer stage C. We set 30 eligible patients as the population for analysis. The final analysis performed with a median follow-up duration of 517days showed that the frequency of SAEs was 30.0% (95% confidence interval [CI] 14.7–49.4%). ORRs according to RECIST 1.1 and modified RECIST were 40.0% and 46.7%, respectively. Median PFS, TTP, and OS were 240 days (95% CI: 176–526 days), 240 days (95% CI: 176–526 days), and 470 days (95% CI: 256–576 days), respectively. Frequent Grade ≥3 SAEs were blood bilirubin increased (n=3), proteinuria (n=3), hypoalbuminemia (n=2), and hypertension (n=2). Grade ≥3 severe liver-related AEs occurred in 7 patients (23.3%), including blood bilirubin increased (n=3) and esophageal varices hemorrhage (n=2). Grade ≥3 severe immune-related AEs occurred in 2 patients – these were mucositis oral (n=1) and malaise (n=1). The mean Child–Pugh score (±standard deviation) at the start of treatment was 7.2±0.4, and was 7.0±1.0, 7.2±0.9, and 7.6±1.7 at the third and fifth cycles and at the withdrawal study, respectively. Conclusions: Atezo+bev was well-tolerated with demonstrable anti-tumor effects in patients with unresectable HCC and Child–Pugh class B cirrhosis. Additional studies are warranted to confirm the efficacy results of atezo+bev in this patient group. Clinical trial information: jRCTs031210355.
Phase I study of autologous CD8+ and CD4+ transgenic T cells expressing high-affinity KRAS G12V mutation-specific T cell receptors (FH-A11KRASG12V-TCR) in patients with metastatic pancreatic, colorectal, and non-small cell lung cancers with KRAS G12V mutations.
Authors: Rachael A. Safyan, Mary Weber Redman, Andrew L. Coveler, Stacey A. Cohen, Sylvia Lee, Cecilia Yeung, Thomas Schmitt, Aude Chapuis, Philip D. Greenberg, E. Gabriela Chiorean
Journal: Journal of Clinical Oncology (2025)

TPS792 Background: KRAS, the most common driver oncogene in human malignancies, has predictable mutations. 85% of RAS mutations occur at the Glycine (G) 12 position with G12V being amongst the most common. Cancers driven by mutant KRAS include pancreatic (PDAC), colorectal (CRC), and non-small cell lung (NSCLC) malignancies. The prognosis of patients with activating KRAS mutations remains poor. Preliminary anti-tumor activity has been observed with T cell receptor (TCR) T cell therapies targeting KRAS mutations, but durable clinical benefit is lacking. FH-A11KRASG12V-TCR is an autologous CD8+ and CD4+ transgenic T cell product expressing (1) an HLA-A*11-restricted, high affinity KRASG12V mutation-specific T cell receptor (TCR) and (2) the wildtype CD8α/β coreceptor enabling CD4+ T cell recognition of KRAS G12V presented on an MHC class I allele mediating helper T cell activity and cytotoxicity. The TCR sequence is derived from the peripheral blood of a healthy HLA-A*11+ adult based on a strong pre-clinical dataset. Methods: This is an ongoing, investigator-initiated, phase 1, first-in-human, single-center, dose escalation study of FH-A11KRASG12V-TCR. The aims are to evaluate the safety, tolerability, maximum tolerated dose (MTD), and preliminary anti-tumor activity of FH-A11KRASG12V-TCR in patients with advanced PDAC, CRC, and NSCLC who express the HLA-A*11-restricted KRAS G12V mutation. Dose modification is guided by the Bayesian Optimal Interval design (BOIN). Patients are initially treated in cohorts of 3 at each dose level (DL). BOIN will be used to identify the recommended dose for subsequent patients. The planned target doses are 5 x 10 9 transgenic TCR T cells in DL 1 with dose escalation up to 15 x 10 9 transgenic TCR T cells in DL 3. This study enrolls patients who are 18 years or older, HLA-A*11:01-positive, with KRAS G12V mutated metastatic PDAC, CRC, or NSCLC. Patients must have progressed on or be intolerant of at least one line of prior therapies including any targeted therapies indicated for their current malignancy. Patients undergo leukapheresis prior to treatment and receive lymphodepleting chemotherapy with either cyclophosphamide intravenously (IV) and fludarabine IV on days -6, -5, and -4 or bendamustine IV on days -4 and -3. FHA11KRASG12V-TCR is administered IV on day 0. The dose-limiting toxicity observation period is 28 days. Patients may receive an additional FHA11KRASG12V-TCR IV infusion at the same or lower dose as soon as 28 days or up to 1 year after the first infusion. The study is actively recruiting. Clinical trial information: NCT06043713 .
A phase 2 study of amplitude-modulated radiofrequency electromagnetic fields (AM RF EMF) in metastatic pancreatic cancer.
Authors: Ravi Kumar Paluri, Michael Joseph McCormack, Emily Van Meter Dressler, George Yacoub, Austin Neal, Stacie Moore, Laura Mcilwain, Olivia Ogburn, Caio Max Sao Pedro Rocha Lima
Journal: Journal of Clinical Oncology (2025)

TPS790 Background: Patients with advanced pancreatic adenocarcinoma (PDC) that progresses after first-line therapy face limited treatment options. Despite advances in systemic therapy, the prognosis for PDC is dismal, with a five-year overall survival (OS) of about 5% . Due to the high morbidity of this disease, there is a critical need for innovative treatments to improve patient outcomes. TheraBionic P1, a hand-held device, delivers tumor specific radio frequencies via a spoon-shaped antenna placed on the patient's tongue. The FDA and EMA have confirmed the safety of the device for amplitude-modulated electromagnetic field (AM-EMF) therapy. Improved efficacy outcomes were reported with AM RF EMF in other solid organ tumors including pancreatic cancer in preliminary studies. Preclinical and clinical evidence suggests that AM-EMF can inhibit tumor growth and was recently approved for use in hepatocellular cancer. The safety and clinical activity observed with AM RF EMF, paired with the unmet medical need for additional effective therapies in pancreatic cancer, provided a strong rationale for further clinical investigation. This protocol evaluates the efficacy and tolerability of AM RF EMF in combination with standard of care frontline therapy, gemcitabine and nab-paclitaxel for metastatic PDC. Methods: This is an ongoing, single-center, Phase II, non-randomized study using a Simon two-stage minimax design to assess the efficacy of AM-EMF in combination with gemcitabine/nab-paclitaxel as a first-line treatment in metastatic pancreatic cancer. Gemcitabine and nab-paclitaxel are administered per standard care. AM RF EMF are delivered to patients with a spoon-shaped applicator placed on the tongue three daily 60-minute treatments. Patients will be assessed for response every 8 weeks. Treatment is continued until progression or toxicity. The primary objective of this study is to evaluate the efficacy of the combination of nab-paclitaxel, gemcitabine, and AM RF EMF in improving 6-month overall survival rates in patients with metastatic PDC. Secondary objectives evaluate the safety, tolerability, profession free survival, objective response rate and disease control rate. Exploratory objectives evaluate change in CA19-9 and quality of life using FACT-General (FACT-G) and determine any possible correlation with clinical outcomes. Key eligibility includes treatment-naïve, histologically confirmed metastatic PC, age eighteen years old or greater, ECOG 0-1, and optimal organ function. Clinical trial information: NCT05776524 .
Results of a multicenter retrospective cohort study evaluating the safety and efficacy of FTD/TPI plus ramucirumab in advanced gastric cancer (HGCSG2302).
Authors: Ayumu Yoshikawa, Takeaki Nakamura, Kentaro Sawada, Atsushi Ishiguro, Iori Motoo, Yuki Sonoda, Kazuhiro Suzuki, Hiroshi Nakatsumi, Ayumu Hosokawa, Takahiro Ishii, Ken Ito, Michio Nakamura, Kazuteru Hatanaka, Takashi Meguro, Susumu Sogabe, Yusuke Sasaki, Shintaro Nakano, Tetsuhito Muranaka, Satoshi Yuki, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2025)

351 Background: In advanced gastric cancer, trifluridine/tipiracil (FTD/TPI) is one of the standard treatments for later-line chemotherapy. Ramucirumab (RAM), an anti-VEGFR-2 monoclonal antibody, has shown promising efficacy in combination with FTD/TPI in phase II studies conducted in Japan, suggesting that this combination could improve treatment outcomes. However, there remains a paucity of real-world clinical data comparing the efficacy and safety of FTD/TPI monotherapy and FTD/TPI plus RAM combination therapy in general clinical practice. Methods: This retrospective analysis to evaluate safety and efficacy included patients with gastric cancer who were received FTD/TPI plus RAM combination therapy or FTD/TPI monotherapy between August 2019 and March 2023 at 21 institutions. Results: 164 patients were analyzed, 38 patients in the RAM combination group and 126 in the FTD/TPI monotherapy group. The distribution of treatment lines (third/fourth/fifth) was 10/13/15 in the RAM group and 26/54/46 in the monotherapy group, respectively. RAM had been previously administered to 34 patients (89.5%) in the RAM group. Objective response rate and disease control rate were 11.1% / 55.6% (OR 2.0, 95% C.I. 0.84-4.77, p=0.126) in the RAM group and 5.5% /38.5% (OR 2.0, 95% C.I. 0.84-4.77, p=0.126) in the monotherapy group, respectively. Median progression-free survival (PFS) was 3.5 months in the RAM group and 2.1 months in the monotherapy group (HR 0.69, 95% C.I. 0.49-1.02, p=0.06), respectively. Median overall survival (OS) was 8.4 months in the RAM group and 5.8 months in the monotherapy group (HR 0.82, 95% C.I. 0.54-1.25, p=0.350), respectively. Grade 3 neutropenia was reported in 48.6%/52.4% (p=0.707), and there were no significant differences in other adverse event profiles between the two groups. Additionally, in the RAM group, a comparison between patients receiving standard dosing (2 weeks on/2 weeks off; n=7) and those on biweekly dosing (1 week on/1 week off; n=24) showed no notable differences in efficacy or safety. Conclusions: FTD/TPI plus RAM combination therapy showed a trend toward prolonged PFS compared to FTD/TPI monotherapy, but no significant difference in OS.
Effect of homologous recombination deficiency on survival in patients with metastatic colorectal cancer with KRAS mutations.
Authors: Minsoo Kim, Jiwon Lee, Jwa Hoon Kim, Yoon Ji Choi, Soohyeon Lee
Journal: Journal of Clinical Oncology (2025)

252 Background: Metastatic colorectal cancer (mCRC) patients exhibit intertumoral genetic heterogeneity, making it difficult to apply precision medicine. In the molecular genetic profile of mCRC, there are relatively few other gene alterations that significantly impact treatment decisions beyond KRAS and MSI status. We aim to investigate the prognostic impact of Homologous recombination deficiency (HRD)-related genetic alterations in mCRC patients, focusing on how mutation status influences on patient outcomes. Methods: The analysis included 364 mCRC patients who underwent comprehensive genomic profiling at Korea University Anam Hospital from Sep. 2016 to Dec. 2020. HRD was defined by the presence of pathogenic variants in genes including ATM, ATR, BARD1, BRCA1/2, BRIP1, CDK12, CHEK2, FANCA, MRE11A, PALB2, RAD50/51. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. Multivariate Cox proportional hazards regression analyses were performed to assess the independent impact of HRD status. Results: Of the total cohort, 181 of patients (49.78%) harbored KRAS mutations. HRD gene mutations were identified in 38 of patients (10.4%) of patients, predominantly in ATM, BRCA 1/2, ARID1A genes. KRAS-HRD co-mutations were present in 18 of patients (4.7%). There is no significant difference in HRD status between the KRAS mutant and wild-type groups (p=0.73). While first-line treatment PFS was independent of KRAS mutational status (wt 10.8 vs. mut 9.6 months, p=0.31), it was significantly associated with HRD gene mutation status (16.2 vs. 10.6 months, p=0.001). OS was similar with KRAS mutations (34.7 vs. 32.9 months, p=0.72) and HRD mutations (34.7 vs. 39.1 months, p=0.73). However, patients with both KRAS and HRD mutations had significantly worse OS compared to those with either KRAS and HRD mutation (21.3 vs. 36.7 vs. 65.3 months, p=0.034, &lt;0.001). A multivariate analysis was performed to evaluate factors affecting OS in mCRC patients. Among the variables, metastasectomy, which 44% of patients underwent, had a significantly low HR (=0.28) and would contributed to more favorable outcomes when evaluating OS. Neither KRAS nor HRD mutation alone was a significant prognostic factor, but their co-mutation was significantly associated with poor survival (HR=2.39, p=0.048). Conclusions: Poor OS in patients with KRAS-HRD co-mutations, despite metastasectomy, highlights the need for additional treatment strategies beyond surgery. Future studies with larger sample sizes and analyses stratified by metastasectomy status are necessary to strengthen these findings. Variables HR (95% CI) p-value Metastasis site Liver 2.16 (1.60 – 2.92) &lt; 0.001 Peritoneum 1.52 (1.01 – 2.11) 0.013 Bone 1.69 (0.96 – 2.97) 0.067 Metastasectomy 0.28 (0.47 – 0.74) &lt; 0.001 KRAS 1.03 (0.77 – 1.37) 0.826 HRD 0.75 (0.40 – 1.41) 0.367 Co-mutation 2.39 (1.01 – 5.66) 0.048