tbuckley/cabot-search huggingface dataset:
A phase 3, randomized study of adjuvant rilvegostomig plus chemotherapy in resected biliary tract cancer: ARTEMIDE-Biliary01.
Authors: Jia Fan, Tanios S. Bekaii-Saab, Luca A. Aldrighetti, John A Bridgewater, Cristina R. Ferrone, James J. Harding, Masafumi Ikeda, Jennifer J. Knox, Julie Wang, Hamzeh Kayhanian, Xin Chen, Sally Yan Bai, Moritz Wolfgang Drachsler, Do-Youn Oh
Journal: Journal of Clinical Oncology (2024)

TPS4199 Background: Biliary tract cancer (BTC) is a rare but aggressive heterogenous group of gastrointestinal cancers that arise from the intra- or extrahepatic bile ducts (cholangiocarcinoma [CCA]) or the gallbladder (GBC). In early-stage disease following curative resection, adjuvant chemotherapy with a fluoropyrimidine- or gemcitabine-based regimen is usually recommended, however, recurrence rates remain high (e.g. in the BILCAP study, 5-year recurrence-free survival with adjuvant capecitabine was 34%). Immunotherapy is efficacious as adjuvant therapy in other cancer types. Results from the TOPAZ-1 and KEYNOTE-966 studies support combining immunotherapy and chemotherapy in advanced BTC, including in locally advanced non-metastatic disease. Furthermore, dual inhibition of programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) and the novel immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), has shown promising results across multiple tumor types without major increases in high-grade toxicity compared with PD-1 or PD-L1 inhibition alone. Rilvegostomig is an anti-PD-1/-TIGIT bi-specific monoclonal antibody that appears active and well tolerated in non-small-cell lung cancer. ARTEMIDE-Biliary01 will investigate the efficacy of rilvegostomig plus standard of care adjuvant chemotherapy in patients with BTC after curative intent resection. Methods: ARTEMIDE-Biliary01 (NCT06109779) is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, global study to assess the efficacy and tolerability of rilvegostomig IV every three weeks versus placebo in combination with investigator's choice of chemotherapy (capecitabine, S-1 [tegafur/gimeracil/oteracil] or gemcitabine/cisplatin) as adjuvant treatment in patients with BTC after curative intent resection. This study will enroll approximately 750 adults with histologically confirmed adenocarcinoma of the biliary tract (intrahepatic or extrahepatic CCA or muscle-invasive GBC) after macroscopically complete resection (R0 or R1) and an ECOG PS of 0–1. Key exclusion criteria include locally advanced, unresectable, or metastatic disease at initial diagnosis and any anti-cancer therapy for BTC prior to surgery. The primary endpoint is recurrence-free survival, and the key secondary endpoint is overall survival. Additional endpoints include progression-free survival following recurrence, patient-reported tolerability, and safety. Enrollment has begun, and approximately 200 sites will be recruiting globally across Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT06109779 .
Meta-analysis comparing the incidence of serious adverse events, overall survival, and progression-free survival in patients with pancreatic adenocarcinoma harboring unresectable tumors treated with modified FOLFIRINOX or FOLFIRINOX regimen.
Authors: Vuong N. Trieu, Sanjive Qazi, Seymour H. Fein, Anthony Ernest Maida, Tenshang Joh
Journal: Journal of Clinical Oncology (2024)

e16318 Background: The evolution of first-line treatment for advanced pancreatic adenocarcinoma (PDAC) from Gemcitabine-based therapies to FOLFIRINOX-based regimens (fluorouracil, leucovorin, irinotecan, oxaliplatin) have demonstrated significant improvements in survival outcomes, however, this was associated with increased side effects such as neuropathy, fatigue, and diarrhea due to its heightened potency. Modified versions of FOLFIRINOX (mFOLFIRINOX) have since been developed with lower doses and longer breaks between cycles to manage side effects. Methods: To systematically test the efficacy and side effects of mFOLIFINOX treatment, we conducted a meta-analysis relating FOLFIRINOX treatment with modified FOLFIROX on the frequency of Grade 3 or 4 adverse events reported in published literature (9 studies), and Serious Adverse Events (SAE) recorded from clinical trials (17 arms accessed from clinicaltrials.gov) in PDAC patients with unresectable tumors. Results: For adverse events occurring in greater than 10% of patients, significant reductions in the frequency of patients experiencing the following events were observed in PDAC patients treated with mFOLFIRINOX: Neutropenia (29.31 % (226/771 patients across 8 arms) versus 18.8% (144/766 across 8 arms; Fisher Exact test, 2-tailed, P &lt; 0.001)), Anorexia (18.57 % (44/237 across 3 arms) versus 5.39% (18/334 across 3 arms); P &lt; 0.001), Peripheral sensory neuropathy (10.63 % (27/254 across 2 arms) versus 3.45% (4/116 across 2 arms); P = 0.025)), and Fatigue (10.57 % (83/785 across 9 arms) versus 6.77% (55/812 across 8 arms); P = 0.007)). Examination of 8 studies (N = 635) for PDAC patients treated with FOLFIRINOX exhibited a median OS time of 11.37 (Range = 10.07 - 13.9) months. Patients treated with mFOLFIRINOX (N = 475) exhibited a median OS time of 12.8 (10.2 - 14.4) months (Two-sample Wilcoxon test, P = 0.372). Conclusions: In conclusion, modified FOLFIRINOX has maintained similar efficacy while reducing severe adverse events, making it more tolerable for adjuvant treatment after surgery.
Phase 1 study to evaluate safety and preliminary efficacy of padeliporfin vascular targeted photodynamic therapy (VTP) in patients with locally advanced (LA) unresectable pancreatic ductal adenocarcinoma (PDAC).
Authors: Nadine Abi-Jaoudeh, Jennifer Brooke Valerin, David K Imagawa, Dina Preise, Zachary Sacks, Yaniv Cohen, Julia Rothman, Keren Brook, Eyal Morag, Avigdor Joshua Scherz, Inna Krasnopolskaya, Genia Alpert, Vincent Chung, Laleh Golkar Melstrom, Jonathan Kessler
Journal: Journal of Clinical Oncology (2024)

TPS4204 Background: Pancreatic cancer is the third most common cause of cancer death. Surgery offers the best survival rates however only a minority of patients are eligible. Approximately 15-20% of patients are deemed unresectable due to vascular involvement LA. Conversion of unresectable tumors, due to vascular involvement to resectable, is an unmet clinical need. Methods: A novel approach was developed to destroy the tumor encasing the artery combining padeliporfin, a photosensitive drug, locally activated by laser light illumination. The effectiveness of the strategy was confirmed in an orthotopic mouse model. A proof-of-concept study using 12 non-tumor pigs demonstrated an acceptable safety profile. A phase I dose escalation trial (NCT5918783) will be performed to evaluate the safety and maximal tolerated dose (MTD) of laser light dose of padeliporfin VTP. VTP will be delivered through an endovascular fiber integrated in a standard angioplasty balloon. The balloon will be advanced under fluoroscopy to the encased vascular segment of the superior mesenteric artery (SMA) and inflated. Following IV administration of padeliporfin, it will be activated by the laser light. Part A will be a classic 3+3 dose-escalation design to determine the MTD of laser light. The identified MTD will be applied in the Part B for preliminary efficacy evaluation. The primary objectives are to determine safety and MTD and/or recommended phase 2 laser light dose of VTP treatment. Secondary objectives are: rate of surgical conversion; evaluation of the pattern of disease progression (local regional and/or metastatic disease) after VTP based on CT. Standard of care surgery can be performed after 14 days post VTP. Key inclusion criteria: patients with histologically/cytologically confirmed stage III unresectable LA-PDAC in the head/uncinate process of the pancreas, with SMA solid tumor contact ˃180° with measurable disease per RECIST 1.1 and ECOG 0-1. Key exclusion criteria: metastatic disease, other malignancy, photosensitive skin diseases or porphyria, concurrent investigational therapy within past 30 days, medically uncontrolled moderate or severe ascites, previous radiation to pancreas, SMA variants. Recruitment begins in April 2024. Conversion of unresectable locally advanced pancreatic cancer to surgery is a critical unmet need. This phase I trial explores a novel approach to treat the tumor encasement enabling surgery. Clinical trial information: NCT5918783 .
CheMo4METPANC: A randomized phase 2 study with combination chemotherapy (gemcitabine and nab-paclitaxel), chemokine (C-X-C) motif receptor 4 inhibitor (motixafortide), and immune checkpoint blockade (cemiplimab) compared to chemotherapy alone in metastatic treatment-naïve pancreatic adenocarcinoma.
Authors: Gulam Abbas Manji, Michael S. May, Morteza Chalabi, Ilenia Pellicciotta, Sarah Sta Ana, Naomi Sender, Samuel M Pan, Isabelle Ross, Shikun Wang, Benjamin Izar, Linda Wu, Brian William Labadie, Susan Elaine Bates, Qian Shi, Alexander G Raufi
Journal: Journal of Clinical Oncology (2024)

TPS4208 Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) carries a 5-year relative survival of 3%. Immune checkpoint inhibitors have thus far failed to improve outcomes due to an immunosuppressive tumor microenvironment (TME). Signaling through the C-X-C motif chemokine receptor 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12) axis results in exclusion of anti-tumor immune cells in mouse PDAC models. Longitudinal survival studies testing combinations of CXCR4i, aPD-1, and gemcitabine in the KPC mouse model of PDAC demonstrated a survival benefit with the combination of all three agents. Results from a multicenter, investigator-initiated, single arm pilot study evaluating the preliminary safety and efficacy ofMotixafortide (CXCR4i), Cemiplimab (aPD1), Gemcitabine, and Nab-paclitaxel (MCGN) in 11 patients with treatment-naïve mPDAC were recently presented. Seven patients (64%) achieved a partial response, including 6 confirmed partial responses, and 10 patients (91%) had disease control, compared to historic partial response and disease control rates of 23% and 48%, respectively, with gemcitabine and nab-paclitaxel (GN). Preliminary median progression-free survival (PFS) was 9.6 months compared to historic median PFS of 5.5 months with GN. Analysis of paired pre- and on-treatment biopsy samples from demonstrated an increase in CD8+ T-cell density in tumors from all 11 patients treated with MCGN (p=0.007). Based on these promising results, the protocol was amended from a single arm expansion totaling 40 patients to a randomized phase 2 study. Methods: This is an open-label, multicenter, investigator-initiated phase 2 clinical trial. Patients are randomized 2:1 to receive MCGN or GNalone (N=108). The primary endpoint is progression free survival. The study has 80% power to detect an improvement in PFS from 6 to 9.2 months (HR 0.65) with a one-sided alpha of 0.20. One interim analysis for futility is planned when 50% of the PFS events are observed. Secondary objectives include response rate, disease control rate, duration of clinical benefit and overall survival. Patients will undergo optional paired biopsies which will be analyzed in conjunction with samples collected from the phase I pilot study. Exploratory studies include interrogation of the TME using quantitative multiplex immunofluorescence and single-cell RNA sequencing. The randomized phase 2 trial is open to enrollment and one patient has been randomized as of 1/29/2024. Clinical trial information: NCT04543071 .
Effects of Attractive Pickering emulsion gels loaded with oxaliplatin and lactate dehydrogenase inhibitors in hepatocellular carcinoma.
Authors: Chanqi Ye, Ruyin Chen, Qiong Li, Shuaishuai Xu, Jian Ruan
Journal: Journal of Clinical Oncology (2024)

e16235 Background: Oxaliplatin (OXA) can be used as a palliative treatment for advanced hepatocellular carcinoma (HCC). While most patients still have rapid disease progression after OXA due to the drug resistance. The lactate dehydrogenase A (LDHA) inhibitors can reduce the inflammation-induced effects, metastasis, and proliferation potential of cancer cells. The combination of OXA and LDHA inhibitor may be an effective treatment for HCC. Methods: We adopt the water-in-oil attractive Pickering emulsion gel (APEG) to deliver OXA and LDHA inhibitor, GSK2837808A (GSK). OXA is dissolved in water and GSK is dissolved in iodized oil. We injected OXA+GSK@gel into the peritumoral tissues of subcutaneously tumorigenic HCC model mice, then observe the tumor size. Next, we apply immunohistochemical staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay on the dissected tumors to explore the cell proliferation and apoptosis. Meanwhile, flow analysis on the dissected tumors is applied to investigate the tumor immune microenvironment in HCC. Results: This drugs-loaded APEG has good biocompatibility and can release OXA and GSK slowly. OXA+GSK@gel has significant anti-tumor effect on HCC model, which can effectively inhibit tumor cell proliferation and promote tumor cell apoptosis. Meanwhile, flow analysis confirm that it could activate the tumor immune microenvironment in HCC. The infiltration of CD8 + T cells was increased, thereby providing better anti-tumor effect. Conclusions: The results suggest that the APEGs loaded with OXA and GSK can effectively improve the delivery efficiency and enhance the anti-tumor therapy.
Efficacy of platinum chemotherapy agents in adenosquamous carcinoma of the pancreas.
Authors: Vasiliki Michalaki, Antonios Vezakis, George Frangoulidis, Konstantinos Bramis, Thedosios Theodosopoulos, Dina Tiniakos, Manousos Konstandoulakis, Christos Papadimitriou
Journal: Journal of Clinical Oncology (2024)

e16317 Background: Adenosquamous carcinoma of the pancreas (ASCP) is an aggressive, infrequent subtype of pancreatic cancer that combines a glandular and squamous component and is associated with poor survival. Data regarding adjuvant therapy remain controversial. Methods: Patients with advanced PASC from 2005 to 2021 were consecutively included in this retrospective study. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Results: Eighteen PASC patients treated surgically were included (median age, 69.3 years; males, 58.2%). All patients received adjuvant chemotherapy. Ten patients (55%) received newer platinum based regimen combination (FOLFIRINOX) and eight patients (45%) received gemcitabine-based regimens. Platinum based regimen as compared to gemcitabine regimen showed an improvement of overall response rate (42.5% and 12.3 %, p=0.001), PFS (median,10.4 versus 3.1 months, p=0.03) and OS (median, 15.8 vs 6.9 months, p=0.21).Multivariate analysis revealed that, among all patients (n=18), the following factors were independently predictive of poor survival: margin-positive resection (HR =3,15; 95% CI, 1.5-5.9; P&lt;0.001), lymph node involvement (HR =2.9; 95% CI, 1.7 -7.5; P=0.003), and lack of inclusion of a platinum agent in the adjuvant regimen (HR =2.6; 95% CI, 1.5 -4.9; P=0.035). Conclusions: Given the rarity of ASC, optimal management remains poorly defined, particularly in the postoperative period. Therapies based on platinum chemotherapeutics may be preferable to all other chemotherapy regimens.
PBP1510, a novel monoclonal antibody targeting pancreatic adenocarcinoma upregulated factor (PAUF): Phase 1/2a monotherapy and combination with gemcitabine in patients with advanced/metastatic pancreatic cancer.
Authors: Jaime Feliu, Ismael Ghanem, Daniel King, Yun-Yong Park, Jamie Kim, Sumita Pradhan, Jessica Ho, Wei Qi Loh, Kedar Diwakar Mandakhalikar
Journal: Journal of Clinical Oncology (2024)

e16296 Background: PAUF, a protein overexpressed in pancreatic cancer but not in non-cancerous tissues, plays a key role in cancer progression and metastasis. PBP1510 is a novel first-in-class humanized IgG1 monoclonal antibody that binds to and neutralizes PAUF with high specificity and affinity. PAUF-I (NCT05141149) is a first-in-human, multicenter, open-label study in patients with advanced/metastatic pancreatic cancer. Early Phase 1 results are presented here. Methods: Key eligibility criteria for Phase 1 include: locally advanced/metastatic pancreatic cancer; at least 1 previous line of chemotherapy; ECOG 0-1; and measurable disease by RECIST v1.1. A 3+3 dose escalation design is planned for 5 dose levels of intravenous PBP1510 (doses of 1, 3, 6, 10, and 15 mg/kg), either alone (monotherapy cohorts) or in combination with gemcitabine at a dose of 1000 mg/m 2 (combination cohorts), in 28-day cycles. Tumor assessments are performed every 8 weeks from the first dose of PBP1510. Dose is escalated following a safety review committee meeting, if all patients in a cohort complete the dose-limiting toxicity (DLT) observation period (28 days from first dose) without any DLTs. Primary endpoints are safety parameters including treatment emergent adverse events (TEAEs) and laboratory findings. Results: As of January 2024, 6 patients (4 males, 2 females), aged 54-71 years, were enrolled. All patients had stage IV ductal adenocarcinoma and had received at least 2 prior lines of chemotherapy. Five patients received 2 cycles of PBP1510 each at 1 mg/kg or 3 mg/kg based on their cohort. One patient received 1 cycle of PBP1510 at 3 mg/kg. Seventeen TEAEs were assessed to be related to study treatment. The most frequently reported treatment-related TEAE was asthenia (n = 7). Most treatment-related TEAEs were NCI-CTCAE Grade 1 in severity (n = 14). Five serious TEAEs not related to study treatment were reported in 2 patients. There was 1 death reported due to disease progression. No patient discontinued treatment due to TEAEs. No clinically significant abnormalities in ECG, LVEF, and clinical laboratory assessments were reported during the DLT observation period. All patients in the first 2 monotherapy cohorts completed the DLT observation period without any DLTs. Conclusions: PBP1510 was well tolerated by all patients at 1 mg/kg or 3 mg/kg in the first 2 monotherapy cohorts. The next monotherapy (PBP1510, 6 mg/kg) and combination (PBP1510, 1 mg/kg; gemcitabine 1000 mg/m 2 ) cohorts are open for recruitment. Clinical trial information: NCT05141149 .
Neoadjuvant immune-checkpoint blockade therapy combined with TACE for resectable hepatocellular carcinoma with high recurrence risk: A phase II, single-arm clinical trial (MORNING).
Authors: Li Tan, Lixia Xu, Shun-Li Shen, Dongming Li, Yunpeng Hua, Shaoqiang Li, Lijian Liang, Qiang He, Qi Zhou, Wenxuan Xie, Zebin Chen, Jian Wu, Jiaping Li, Wenzhe Fan, Wenquan Zhuang, Lili Chen, Shiting Feng, Sui Peng, Jiping Wang, Ming Kuang
Journal: Journal of Clinical Oncology (2024)

e16267 Background: Prognoses of patients with hepatocellular carcinoma (HCC) remain unsatisfactory due to the high recurrence rate after curative hepatectomy. In this study, we investigated the safety and efficacy of neoadjuvant Cadonilimab (PD-1/CTLA-4, a bi-specific antibody) in combination with transarterial chemoembolization(TACE) for patients with high recurrence risk. Methods: For this phase II, single-centre, single-arm trial, resectable HCC (BCLC stage A/B) participants were enrolled, who should meet at least one of the following high-risk criteria: a) Multiple tumors or satellite lesions (≥2); b) tumor diameter&gt;5cm (single tumor); c) AFP ≥ 400 ug/L; d) Predicted to be positive by the Microvascular invasion prediction model of our center according to preoperative imaging. All of the patients received two cycles of Cadonilimab(10mg/kg, Q3W) after TACE treatment. After resection, patients received additional 12 months of Cadonilimab(10mg/kg, Q3W) in the adjuvant setting. The primary end-point was the major pathologic response (MPR, defined as &gt;90% necrosis of the resected tumour), the secondary endpoints are objective response rate (ORR), one-year recurrence rate and safety. Results: Between Apr 26th, 2023, and Jan 5th, 2024, 19 patients were enrolled, 84.2% of whom were male, with the mean age of 55. 9(47.4%) patients had more than one tumor and 13(68.4%) patients had tumors larger than 5cm. All patients received neoadjuvant TACE and at least one cycle of Cadonilimab. Of the 15 patients underwent successful resection, 7(46.7%) had MPR, while 12(80%) of them had 70% or greater tumour necrosis. 11 patients had partial response and the ORR was 73.3% per mRECIST. Additionally, only one patient received a partial response, while twelve patients maintained stable decease as assessed by RECIST1.1. 19(100%) patients had treatment-related adverse events of any grade during the neoadjuvant treatment period. The most common adverse events of any grade were ALT/AST increase (94.7%), abdominal pain (73.7%) and bilirubin increase (57.9%). 4 patients had grade 3 adverse events, including infusion reaction (2 patients), white blood cell decreased (2 patients) and fever (1 patients). The abdominal pain and fever were more relevant to TACE. No grade 4 or 5 events were observed. Conclusions: Cadonilimab combined with TACE as a neoadjuvant therapy seems to demonstrate safety and promising efficacy. Clinical trial information: NCT05578430 . [Table: see text]
A randomized, open-label phase II/III efficacy and safety study of atezolizumab in combination with FLOT versus FLOT alone in patients with gastric cancer and adenocarcinoma of the oesophagogastric junction and high immune responsiveness: The IKF633/DANTE trial, a trial of AIO in collaboration with SAKK.
Authors: Salah-Eddin Al-Batran, Sylvie Lorenzen, Vera Heuer, Stefan Angermeier, Thomas Jens Ettrich, Nils Homann, Georg Martin Haag, Annika Kurreck, Alexander Stein, Volker Heinemann, Ulrich Ronellenfitsch, Thomas Zander, Stefan Kubicka, Alexander Rheinhard Siebenhuener, Christina Kopp, Claudia Pauligk, Thorsten Goetze
Journal: Journal of Clinical Oncology (2024)

TPS4184 Background: Despite recent advances, long-term survival of patients with locally advanced, operable esophagogastric adenocarcinoma (EGA) is below 50%. Immune checkpoint inhibitors in the neoadjuvant setting of this tumor type have lately been shown to increase pathological responses in all comers (IKF633/DANTE pII, KEYNOTE-585, Matterhorn), but the effect on survival is still unknown. The IKF633/DANTE pIII trial evaluates the efficacy and clinical activity of atezolizumab (ATZ) with perioperative FLOT in patients (pts) with locally advanced, resectable EGA considered having an immune-responsive profile. Methods: IKF633/DANTE is conducted as a randomized, multinational, multicenter, prospective, investigator-initiated, open label phase II/III trial. For the phase III portion, pts with histologically confirmed EGA of a clinical stage ≥cT2 and/or cN+ without evidence of distant metastases and with at least one immune response criterium (MSI, PD-L1 CPS≥1, TMB ≥10/MB or EBV+) are eligible. Pts are stratified acc. to nodal stage (cN- vs. cN+), tumor site (GEJ type I vs. GEJ type II/III vs. gastric) and PD-L1 expression levels (CPS≥5 vs. CPS&lt;5). Pts are randomized 1:1 to receive 4 pre- and post-operative cycles FLOT/ATZ, followed by 8 cycles ATZ maintenance (Arm A) or 2x4 perioperative cycles FLOT alone (Arm B). In total, 556 pts will be enrolled, thereof 379 pts in phase III. This estimates to a recruitment time of 30 months plus 18 months follow-up for 80% statistical power and a significance level of p&lt;0.05 (two-sided log rank test). The primary endpoint is event-free survival (EFS) with a target hazard ratio of 0.72, reflecting a clinically relevant improvement to 41.65 months in arm A. Main secondary endpoints are pCR, overall survival (OS) also in high immune-responsive subgroups (CPS ≥5/ CPS≥ 10/ MSI), R0 resection rate and safety/tolerability. In addition, a prospective biomarker study with serial circulating tumor DNA (ctDNA) analysis accompanying therapy is performed to explore the prognostic impact of ctDNA on efficacy and survival parameters, as well as on relapse incidence. Recruitment of phase III started in Aug 2023 and is still ongoing. Clinical trial information: NCT03421288 .