bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of XmAb20717 (vudalimab) in patients with advanced biliary tract cancers.
Authors: Chapin William Joseph , Agarwal Parul , DiCicco Lisa , Palmer Rayleigh , Cenou Nadia , Huang Alexander Chan Chi , Karasic Thomas Benjamin 
Published: June 2023

TPS4184 Background: For patients with advanced biliary tract cancers (BTCs), gemcitabine and cisplatin has been the standard-of-care first-line therapy, with a median overall survival (OS) of 11.7 months. More recently, TOPAZ-1 demonstrated a modest, but significant overall survival benefit (HR 0.80; 95% CI 0.66 – 0.97) to the addition of durvalumab to gemcitabine and cisplatin with a median OS of 12.8 months. However, for patients without targetable molecular variants, second-line and beyond options are limited, with FOLFOX demonstrating an overall response rate (ORR) of 5% and increase in median overall survival by 0.9 months compared to active symptom control. In patients with advanced BTCs, combination immunotherapy approaches with PD-1 or PD-L1 plus CTLA-4 inhibitors have been associated with improved ORRs of 10.8% - 23% compared to ORRs of 3 – 7% observed with single agent PD-1 or PD-L1 inhibitors. XmAb20717 (vudalimab) is a novel, bispecific antibody targeting PD-1 and CTLA-4 which demonstrated an ORR of 14.1% in a phase I dose expansion cohort of patients with advanced malignancies, including patients that had experienced disease progression on prior immune checkpoint inhibitors. Methods: We initiated a single-arm, phase II clinical trial with a Simon two-stage mini-max design to evaluate the efficacy of XmAb20717, in terms of ORR, in patients with advanced biliary tract cancers previously treated with gemcitabine-based chemotherapy. In the first stage, 13 patients evaluable for efficacy will be accrued. If no responses are observed in these 13 patients, the study will be stopped for futility. Otherwise, 14 additional patients evaluable for efficacy will be accrued to total 27 evaluable patients. If 4 or more responses are observed in these 27 patients, then the null hypothesis will be rejected. XmAb20717 (10 mg/kg) is administered intravenously on days 1 and 15 of a 28-day cycle. Important inclusion criteria include that patients with FGFR2 fusions, NTRK fusions, or IDH1 mutations must have received molecularly targeted therapy unless contraindicated or refused. Patients are not eligible if they have received prior immune checkpoint inhibitor therapy. Correlative studies will include longitudinal peripheral blood collection for circulating immune cell profiling. As of January, 2023, 8 patients have been enrolled with enrollment ongoing. Clinical trial information: NCT05297903 .
NeoTACE: A multicenter, randomized study evaluating the efficacy and safety of neoadjuvant HAIC for TACE plus donafenib in BCLC B stage hepatocellular carcinoma outside of up-to-seven.
Authors: Wang Xiaodong 
Published: June 2023

TPS4186 Background: Transarterial chemoembolization (TACE) is standard treatment for hepatocellular carcinoma (HCC) patients in BCLC B stage, while a number of studies demonstrated compromised effect of TACE for patients with large HCC or tumor burden outside of up-to-7. Recently, two phase 3 studies showed the survival benefit of Hepatic arterial infusion chemotherapy (HAIC) for large HCC and as neoadjuvant treatment for HCC outside of Milan criteria. A Phase 3 study also showed the survival benefit of donafenib for unresectable HCC compared with sorafenib. Here, we propose a prospective randomized study to investigate the benefit of HAIC as a neoadjuvant therapy for TACE plus donafenib in unresectable BCLC B stage HCC outside of up-to seven. Methods: This is a multicenter, open-label, randomized study designed to evaluate the efficacy and safety of neoadjuvant HAIC for TACE plus donafenib compared with TACE plus donafenib in BCLC B stage unresectable HCC outside of up-to-seven. Participants are randomized in 1:1 ratio to either Arm A, receiving 2-4 cycles neoadjuvant HAIC treatment plus donafenib initially, then TACE plus donafenib sequentially, or Arm B, just receiving TACE treatment plus donafenib. HAIC consisted of infusions of oxaliplatin (35 mg/m2 for 2 hours), followed by 5-fluorouracil (600 mg/m2 for 22 hours) on day1-3 every 4 weeks. The primary endpoint is PFS, and the secondary endpoints are OS, ORR, DCR, and adverse events. We hypothesize that neoadjuvant HAIC for TACE plus donafenib will improve PFS from 6 months to 11 months, with the hazard ratio of 0.55. With one-sided significance level of 0.05 and power of 0.8, the sample size for randomization will be 156. The study, registered with clinical trial ID of NCT05171166, started enrolment in Feb 2022. As of Oct 2022, 65 patients have been enrolled and 11 patients have been randomized. Clinical trial information: NCT05171166 .
ADJUBIL: A phase II study of immunotherapy with durvalumab and tremelimumab in combination with capecitabine or without capecitabine in adjuvant situation for biliary tract cancer.
Authors: Goetze Thorsten Oliver , Kochen Lisa , Vortmeyer Doerthe , Al-Batran Salah-Eddin , Habibzada Timorshah , Brunner Marius , Ettrich Thomas Jens , Gonzalez-Carmona Maria A , Kohne Claus-Henning , Modest Dominik Paul 
Published: June 2023

TPS4187 Background: Despite improvements in multidisciplinary management, patients with biliary tract cancer (BTC) have a poor outcome. Only 20% of patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. Data regarding pure adjuvant chemotherapy in BTC’s are conflicting and the SOC of the western world is currently capecitabine according to the British BILCAP- trial, even though BILCAP was formally negative. Based on the positive data for durvalumab in the TOPAZ- 1 – trial in BTC and for STRIDE- regimen in HCC according to the Himalaya- data, evaluation of IO- combination in the adjuvant setting seems to be promising. Preclinical studies indicate that the antibody combination results in stronger and more durable anti-tumor effects than single therapies by synergistically modulating the immunosuppressive tumor microenvironment which is particularly rich in cholangiocarcinoma. The aim of this study is the assessment of the clinical activity of the anti-PD-L1 (programmed- death 1-ligand) antibody durvalumab and the anti-CTLA-4 (cytotoxic T- lymphocyte-associated antigen 4) antibody tremelimumab in combination with or without capecitabine in patients with respectable BTC in the adjuvant situation. This is a randomized phase II study as a proof-of-concept for a potentially larger research program. Methods: The ADJUBIL trial is an open-label, multicenter phase II study, including patients with BTC after curative surgery with no previous systemic treatment. Patients are randomly assigned to receive tremelimumab (300mg, one dose) plus durvalumab (1500mg every 4 weeks; STRIDE, for a maximum of 12 months), with or without capecitabine (for 8 cycles). Forty evaluable patients will be enrolled in the study (1:1) to receive anticancer treatment until disease recurrence or intolerable toxicities. Primary objective is to assess the anti-tumor activity of the treatment in both arms by the recurrence-free survival rate after 12 months (RFS@12). Secondary endpoints are recurrence-free survival, overall survival, toxicity, and quality of life. Exploratory endpoints: Explore predictive biomarkers for recurrence-free survival and overall survival. Study start of the ADJUBIL trial was in June 2021. By January 2023, 12 centers across Germany have been initiated and a total of 8 out of 40 planned patients (1:1) have been enrolled. The study is currently ongoing. Clinical trial information: EUCTR2021-002389-41 .
Durvalumab and tremelimumab for hepatocellular carcinoma in patients listed for a liver transplant.
Authors: Sohal Davendra , Abouelezz Khaled Fahmy , Moreland Katie , Quillin Ralph , Lemon Kristina , Rojan Adam , Olowokure Olugbenga Olanrele , Kord Ali , Shah Shimul 
Published: June 2023

TPS4188 Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy, developing most often in the setting of liver cirrhosis (Sohal et al Current Oncol Rep 2011; Gordan et al JCO 2020). For advanced disease, immunotherapy has now become standard of care – a combination of atezolizumab and bevacizumab has shown the best overall survival outcome so far (Finn et al NEJM 2020). For earlier stage disease, however, there is no systemic therapy standard. The best treatment for HCC in the setting of cirrhosis is a liver transplant allowing potential cure for both the cancer and cirrhosis. Nonetheless, 25-35% of patients fail to reach liver transplant because of disease progression while waiting for a transplant (Sinha et al, Hepatology 2019) and approximately 15% experience HCC recurrence after transplant (Mehta et al, Transplantation 2020). Taken together, this constitutes a large subset of this patient population who cannot achieve a cure. Given the success of immunotherapy in the advanced setting, it is imperative to study this in the pre-transplant setting, to improve the outcomes cited above. However, there is a theoretical risk of graft rejection with immunostimulatory treatment. Methods: This is a single-arm, open-label, Phase II, multicenter study designed to evaluate the safety and efficacy of durvalumab and tremelimumab for the treatment of HCC patients who have cirrhosis or portal hypertension and are eligible for listing for a liver transplant. Eligibility requirements include adult patients with HCC within UCSF criteria, a Child-Pugh score of up to 7, and ECOG PS of 0 or 1. Treatment includes an immunotherapy combination of 1 dose of tremelimumab and 5 doses of durvalumab for up to 4 months. After a minimum 28-day gap following the final durvalumab dose, patients undergo locoregional therapy per institutional standards. After a minimum 72-day gap from the end of immunotherapy, patients undergo liver transplant. Primary outcome is a binary endpoint, and it will be assessed in patients undergoing liver transplant. Historically, 10-20% of patients are expected to experience acute cellular rejection within 30 days of transplant. We propose that an observed proportion of 20% treatment failure will be a clear indicator of safety in this pilot study, whereas an observed proportion of 50% failure will be a clear indicator of failure. Using these guardrails, with at least 20 patients going to transplant, we will have 80.6% power to demonstrate a failure proportion of 20% (4 patients experiencing failure) versus a null of 50% (10 patients experiencing failure), with a one-sided alpha of 0.05. With 25 patients going to transplant, the power will increase to 86% (other parameters being the same). Clinical trial information: NCT05027425 .
An open-label window of opportunity trial to evaluate the activity of durvalumab and tremelimumab with platinum-based chemotherapy (gemcitabine and cisplatin) in intrahepatic cholangiocarcinoma.
Authors: Gbolahan Olumide B. , Akce Mehmet , Outlaw Darryl Alan , Williams Grant Richard , Reddy Sushanth , Denbo Jason , Kim Richard D. , El-Rayes Bassel F. , Rose J. Bart 
Published: June 2023

TPS4189 Background: Following surgical resection, the rate of recurrence of intrahepatic cholangiocarcinoma (ICC) is high. Expert groups recommend preoperative systemic therapy, particularly for resectable ICC with features that portend a high risk of recurrence. Based on data from ABC-02 the combination of gemcitabine and cisplatin (GC) is often used. This provides an objective response rate (ORR) of only 20% in ICC. The addition of durvalumab, an anti-PDL1 inhibitor to GC improves overall survival (OS) in the metastatic setting and is associated with an ORR of about 30%. On the other hand, while the addition of nab-Paclitaxel to GC provides an ORR of 34%, it was not associated with an improvement in OS in biliary tract cancer. It is therefore rationale to continue to explore and optimize immune checkpoint inhibitor development in ICC. We designed this study to determine the activity of durvalumab (D) and tremelimumab (T) (anti-CTLA4 ICPI) in combination with GC in resectable ICC with high-risk features. We plan to explore tumor intrinsic and tumor microenvironment related factors that will be associated with response (or lack thereof) to ICPI. Methods: This is a multicenter open-label, window of opportunity trial of the combination durvalumab and tremelimumab in combination with GC in resectable ICC with high-risk features. Inclusion criteria includes patients ≥18years with radiologically measurable and biopsy proven ICC that is surgically resectable but with high risk features (based on multidisciplinary tumor board discussion). Prespecified high-risk features include tumor size >5cm, T1b-T4 lesion, multifocal tumors/tumor with satellite lesions, suspicious or involved lymph nodes (N1) and vascular involvement all thought to be technically resectable. Patients with extrahepatic metastasis will be excluded. D will be administered at 1500mg IV on Day 1 every 3 weeks for up to a maximum of 4 cycles. T, 300mg will be administered on Day 1 of cycle 1 only. G (1000mg/m2) and C (25mg/m2) will be administered by IV infusion on Days 1 and 8 every 3 weeks for a maximum of 4 cycles. The primary outcome measure is to demonstrate an ORR of 52%. Secondary objectives are to assess the feasibility and safety of the combination in ICC. Given the historical objective response rate of 25% and using one-sided exact test for single proportion, we will have 80% power to reject 25% ORR at α=0.05 when we observe ORR of 52% (Ho: Po=0.25 vs. Ha: Pa=0.52) from the study sample. The study is open at the O’Neal Comprehensive Cancer Center at the University of Alabama and will be open at other centers in the next few months. Clinical trial information: NCT04989218 .
A phase II, open-label pilot study evaluating the safety and activity of liposomal irinotecan (Nal-IRI) in combination with 5-FU and oxaliplatin (NALIRIFOX) in preoperative treatment of pancreatic adenocarcinoma: NEO-Nal-IRI study.
Authors: Rogers Sherise C. , Sahin Ilyas , Fabregas Jesus C. , Nassour Ibrahim , Ramnaraign Brian Hemendra , Hitchcock Kathryn , Hughes Steven J. , Lee Ji-Hyun , Kayaleh Omar Roger , Turk Anita Ahmed , Fan Z. Hugh , Russell Karen Bullock , DeRemer David L. , Allegra Carmen Joseph , George Thomas J. 
Published: June 2023

TPS4190 Background: Neoadjuvant treatment for potentially curable pancreatic cancer (PDAC) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Liposomal irinotecan injection (Nal-IRI) is FDA approved with a well-tolerated safety profile in relapsed, refractory metastatic PDAC. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen (NALIRIFOX) and to demonstrate safe and effective neoadjuvant delivery. Methods: This phase 2, open-label, multicenter single-arm study focuses on patients (pts) with operable PDAC without metastatic disease. Other key eligibility criteria include age ≥18 years, resectability confirmed by multidisciplinary GI tumor board (resectable vs. borderline), adequate cardiac, renal, hepatic function and ECOG performance status of 0 to 1. Pts receive NEO-N-IRI regimen as per Table every 2 weeks for four months followed by disease reassessment. Pts who remain surgical candidates will undergo surgical resection within 4 to 8 weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life during treatment as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable pts to demonstrate a reduction in historical 30-day postoperative complication rate. Microbiota specimens will be collected for exploratory analysis. Clinical trial information: NCT03483038 . [Table: see text]
Phase II trial of BXCL701 and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (EXPEL-PANC).
Authors: Weinberg Benjamin Adam , Gutierrez Martin , Tesfaye Anteneh A. , Tan Ming Tony , Noel Marcus Smith , He Aiwu Ruth , Mukherji Reetu , Marshall John , Gleim Jennifer , Bouker Kerrie , Weiner Louis M. 
Published: June 2023

TPS4194 Background: Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options and is thought to be a “cold” tumor that does not respond to immunotherapy, due to a tumor microenvironment (TME) consisting of a desmoplastic stroma and poor T cell infiltrate. BXCL701 is an oral synthetic dipeptide that competitively inhibits dipeptidyl peptidases DPP4, DPP8, DPP9 and fibroblast activation protein (FAP). BXCL701 exerts antitumor activity via inhibition of DPP8/9, which is associated with induction of proinflammatory cytokines, as well as inhibition of FAP, which disrupts tumor-stromal interactions. Preclinical xenograft models demonstrate synergy between BXCL701 and an anti-PD-1 monoclonal antibody, reducing tumor growth and promoting an increase in intratumoral CD4+ and CD8+ T cells and NK cells. The combination of BXCL701 and pembrolizumab is already being studied in a phase II trial in patients with prostate cancer (NCT03910660) and a multi-cohort basket study (NCT04171219). Methods: This is a phase II trial of BXCL701 administered at 0.2 mg PO BID days 1-7 and 0.3 mg BID days 8-14 during cycle 1 (21 days) followed by 0.3 mg BID days 1-14 every 21 days in all subsequent cycles, given with pembrolizumab 200 mg IV every 21 days (all cycles). The primary objective is to determine the 18-week progression-free survival rate (PFS18weeks) in patients with metastatic PDAC treated in the second-line setting. We estimate that historical 2nd-line PFS18weeks is 30% or less; using a Simon’s two-stage (minimax) design, a type I error rate of 0.05 and power of 80% when the true response rate of 50%, we will need 19 patients in stage 1 and 20 in stage 2 (a total of 39). We plan to enroll 43 patients to account for a predicted 10% drop out of unevaluable patients. Eligible patients must have metastatic PDAC and disease progression or intolerance to only 1 line of therapy for metastatic disease, without exposure to prior immunotherapy. Patients must have measurable disease amenable to serial biopsies. Correlative pharmacodynamic studies include imaging mass cytometry to examine 34 markers of the PDAC TME in tissue biopsies, as well as blood-based analyses of KRAS circulating tumor DNA, circulating markers of fibrosis, and IL-6. Enrollment began in Q1 2023. Clinical trial information: NCT05558982 .
ASCEND: A randomised, double-blinded, phase II study of gemcitabine and nab‐paclitaxel with CEND‐1/LSTA1 or placebo in patients with untreated metastatic pancreatic ductal adenocarcinoma.
Authors: Dean Andrew Peter , Price Timothy Jay , Sjoquist Katrin Marie , Gebski Val , Mumford Jan , Day Fiona , Yip Sonia , Bradshaw Nathan , Jackson Christopher G. C. A. , Padinharakam Shamsudheen , Lee Belinda , Burge Matthew E. , Tebbutt Niall C. , Steer Christopher B. , Lomma Chris , Lam Lyn , Lee Joanna , Chantrill Lorraine A. , Harris Marion 
Published: June 2023

TPS4197 Background: LSTA1 is a novel cyclic peptide with high tumor vascular endothelium specificity that activates an endocytotic/exocytotic transport pathway on stroma and tumor. LSTA1 potentiates greater intratumoral access for co-administered or tethered anti-cancer agents, including small molecules, antibodies, and nanoparticles, leading to increased anti-neoplastic activity. Preclinical studies in solid tumor models have shown co-administrating LSTA1 is effective in augmenting the delivery and activity of multiple anti-cancer agents. LSTA1 has been evaluated in 31 patients in a Phase I study in metastatic pancreatic ductal adenocarcinoma (mPDAC) demonstrating an objective response in 59% of patients, a 79% disease control rate at 16 weeks with a median progression free survival (PFS) of ~9.9 months. No dose limiting toxicities were observed. The ASCEND study will determine whether LSTA1 when added to SOC chemotherapy is active and safe as first-line treatment of mPDAC, and whether an additional dose of LSTA1 administered approximately 4 hours after chemotherapy further improves anti-cancer activity. Methods: ASCEND is a randomized, double-blind, placebo-controlled phase II trial evaluating the safety and efficacy of LSTA1 3.2 mg/kg in combination with standard of care chemotherapy (nab-paclitaxel 125mg/m2 and gemcitabine 1000mg/m2 on days 1, 8, and 15, every 28 days) in patients with histologically proven, previously untreated mPDAC. A total of 155 subjects will be randomized 2:1 in favor of study intervention in two cohorts and stratified by age, ECOG status, presence of liver metastasis, and study site. Patients in cohort A receive single doses of LSTA1 or placebo, and for cohort B, two doses of LSTA1 or placebo spaced 4 hours apart. Tumour assessment occurs every 8-weeks from randomization until disease progression or commencement of a new anti-cancer therapy. The primary endpoint is PFS. Secondary endpoints include objective tumour response safety, overall survival, and patient reported outcomes. At 14 Feb 2023, 70 participants have been enrolled from Australian sites. Sites in Ireland and New Zealand are anticipated to open this year. Clinical trial information: NCT05042128 .