bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perioperative MVT-5873, a fully human monoclonal antibody against a CA 19-9 epitope, for operable CA 19-9 producing pancreatic cancers, cholangiocarcinomas, and metastatic colorectal cancers.
Authors: Gupta Shreya , McDonald James D , Ayabe Reed I , Khan Tahsin M , Gamble Lauren A , Rossi Alexander J , Sinha Surajit , Hannah Cathleen , Mabry-Hrones Donna , Monge B. M. Cecilia , Blakely Andrew M. , Greten Tim F. , Davis Jeremy L. , Hernandez Jonathan M 
Published: May 2020

TPS4655 Background: Operable hepatopancreatobiliary (HPB) cancers continue to pose significant challenges. Radical resections are rarely curative, and chemotherapy is able to reduce tumor recurrence for only a fraction of patients. Despite the obvious advantages of extirpation of the identifiable tumor(s), the inflammatory milieu that accompanies surgery and the obligate time off cytotoxic agents allows for activation of remote quiescent disseminated tumor cells, leading to metastatic recurrence. We are conducting a study to determine the safety and efficacy of immediate peri-operative MVT-5873, a cytotoxic monoclonal antibody targeting Carbohydrate Antigen 19-9 (CA 19-9), in patients undergoing resections pancreatic cancer, cholangiocarcinoma or metastatic colorectal cancer to the liver. MVT-5873 is a human IgG1 antibody isolated from a patient following immunization with a sLea-KLH vaccine. MVT-5873 has demonstrated cell surface binding in sLea positive human tumor lines and has been shown to be potent in complement-dependent cytotoxicity assays and antibody-dependent cell mediated cytotoxicity assays. In patients with CA 19-9-producing cancers, MVT-5873 treatment has been shown to decrease serum CA 19-9 levels and prevent tumor progression. This trial may open the door for investigation of additional and/or synergistic agents in the immediate peri-operative period and usher in a new paradigm in the management of surgically treated cancers. Methods: This is a prospective, Phase II trial designed to determine the efficacy (increase in 1-yr DFS) and safety of peri-operative MVT-5873 for subjects with operable pancreatic, liver and bile duct cancers with elevated CA 19-9 levels. Patients may receive any standard neoadjuvant regimen prior to enrollment at the NIH Clinical Center in Bethesda, Maryland. Eligible patients will receive a pre-operative dose of MVT-5873 three days prior to the planned operation to remove all demonstrable disease. Following the operation, patients will receive a total of four doses of MVT-5873; the first two doses on postoperative days four and ten. The third dose will be administered on the normally scheduled postoperative clinic visit, followed by a final dose one month after discharge from the hospital and prior to the start of adjuvant treatment. Clinical trial information: NCT03801915 .
TRYbeCA-1: A randomized, phase III study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441).
Authors: Hammel Pascal , Berardi Rossana , Creemers Geert-Yan , Cubillo Antonio , Van Cutsem Eric , Greil Richard , Macarulla Teresa , Metges Jean-Philippe , Noel Marcus Smith , Nygren Peter , Osterlund Pia J. , Seufferlein Thomas , Wasan Harpreet Singh , Gupta Anu , Grummer Linda Marie , Biswas-Baldwin Nigel , Kay Richard , Youssoufian Hagop , El-Hariry Iman , Hidalgo Manuel 
Published: May 2020

TPS4666 Background: Second-line treatment options for advanced pancreatic adenocarcinoma are currently limited. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs) is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. We have recently reported the outcome of a randomized Phase 2b study inpatients with advanced pancreatic cancer whose disease progressed following first-line treatment(NCT02195180). Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression free survival (PFS). The safety profile of eryaspase was acceptable. The results of this Phase 2b study provided a rationale for initiating this confirmatory Phase 3 pivotal trial (TRYbeCA-1). Methods: TRYbeCA-1 is a randomized, open-label Phase 3 trial (N = ~500) of eryaspase combined with chemotherapy in patients with adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria include performance status 0 or 1; stage III-IV disease; documented evidence of disease progression; available tumor tissue; and adequate organ function. The primary endpoint is OS. Key secondary endpoints include PFS and objective response rate, safety, quality of life, pharmacokinetics and pharmacodynamics, and biomarker research. A hazard ratio in OS of 0.725 is being targeted which represents a conservative estimate based on the Phase 2b data and is viewed as being highly clinically relevant. An IDMC is established to review safety at regular intervals andto review efficacy data at the planned interim and final analyses. IDMC last reviewed the trial in October 2019 and suggested the trial continue as planned. Clinical trial information: NCT03665441 .
Phase II, open-label, randomized study of first-line zolbetuximab plus gemcitabine and nab-paclitaxel (GN) in Claudin 18.2–positive metastatic pancreatic cancer (mPC).
Authors: Park Wungki , O'Reilly Eileen Mary , Furuse Junji , Kunieda Futoshi , Jie Fei , Kindler Hedy L. 
Published: May 2020

TPS4667 Background: Combinations of folinic acid, fluorouracil (5-FU), irinotecan, and oxaliplatin (FOLFIRINOX) along with GN are standard first-line treatment options for mPC. Despite treatment advances, mPC has a poor prognosis with a 5-year survival rate of < 5%, emphasizing an urgent need for new targeted therapeutics. Claudin 18.2 (CLDN18.2) is a tight junction protein restricted to normal gastric mucosa cells; however, in the context of malignant transformation, CLDN18.2 is frequently expressed in carcinomas derived from organs that do not normally express it, such as pancreatic adenocarcinoma (50-70% express CLDN18.2). Zolbetuximab is a chimeric IgG1 monoclonal antibody that specifically binds to CLDN18.2, designed to mediate cancer cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Methods: This phase 2 study (NCT03816163) with a safety lead-in phase will assess safety and antitumor activity of zolbetuximab plus GN in patients (pts) with histologically confirmed mPC with high CLDN18.2 expression (≥75% of tumor cells demonstrate moderate-to-strong IHC staining). The safety lead-in will assess safety/tolerability of zolbetuximab (n = 3 at 1,000 mg/m2 on Cycle 1 Day 1 then 600 mg/m2 Q2W then expand/de-escalate using a 3+3 design) plus GN and confirm the recommended phase 2 dose (RP2D). Dose-limiting toxicities (DLTs), defined as a specified toxicity that occurs during the DLT assessment period and is related to zolbetuximab, will be assessed after Cycle 1 (28 days). After determining the RP2D, approximately 129 pts will be randomly assigned 2:1 to receive either zolbetuximab RP2D Q2W on Days 1 and 15 plus GN on Days 1, 8, and 15 of each cycle ( Arm 1), or GN alone on Days 1, 8, and 15 of each cycle ( Arm 2). Randomization will be stratified by ECOG performance status (0 or 1) and liver metastasis (yes or no). Imaging (CT/MRI) will be performed at baseline and every 8 weeks until investigator-assessed disease progression (per RECIST v1.1 criteria) or the start of other systemic anticancer treatment, whichever comes earlier. Primary objectives are to confirm RP2D (safety lead-in), to assess antitumor activity measured by overall survival (randomization phase), and to establish the safety/tolerability profile of zolbetuximab plus GN across the study. Key secondary endpoints in the randomization phase are progression-free survival and objective response rate. As of January 2020, this study is recruiting pts at 74 centers. Clinical trial information: NCT03816163 .
A phase II, randomized study of nivolumab (NIVO), NIVO plus linrodostat mesylate, or NIVO plus intravesical bacillus Calmette-Guerin (BCG) in BCG-unresponsive, high-risk, nonmuscle invasive bladder cancer (NMIBC): CheckMate 9UT.
Authors: Hahn Noah M. , Chang Sam , Meng Maxwell , Shore Neal D. , Konety Badrinath R. , Steinberg Gary D. , Gschwend Juergen , Nishiyama Hiroyuki , Palou Joan , Taylor John A , Lambert Alexandre , Zhu Li , Maeda Toshiki , Raybold Bradley , Fischer Bruce S. , Jeyamohan Chandrika , Zardavas Dimitrios , Witjes Fred 
Published: May 2020

TPS5090 Background: Immune checkpoint inhibitors, including NIVO (anti–PD-1), have demonstrated favorable tolerability and efficacy profiles, ushering in a new treatment (tx) paradigm for advanced bladder cancer (advBC). However, an unmet need exists for new effective tx options in earlier stages of disease, specifically for patients (pts) with BCG-unresponsive, high-risk NMIBC. Increased IDO and PD-L1 expression in NMIBC tumors (Inman, et al. Cancer 2007; Hudolin, et al. Anticancer Res 2017), support the combination of anti–PD-1 and IDO1 inhibition in NMIBC. Linrodostat mesylate, a selective, potent, once-daily IDO1 inhibitor, has demonstrated clinical activity in combination with NIVO in pts with immunotherapy-naive advBC who received ≥ 1 prior line of therapy (objective response rate, 37%; Tabernero, et al. J Clin Oncol 2018;36(suppl) [abstr 4512]). Furthermore, high levels of PD-L1 expression have been reported in patients not responding to BCG tx. These findings provide a rationale for investigation of NIVO ± linrodostat ± intravesical BCG therapy in BCG-unresponsive high-risk NMIBC. Here we describe a phase 2, randomized, open-label study assessing the safety and efficacy of NIVO ± linrodostat ± intravesical BCG in pts with BCG-unresponsive, high-risk NMIBC (NCT03519256). Methods: Pts aged ≥ 18 years with BCG-unresponsive (per February 2018 FDA guidance), high-risk NMIBC, defined as carcinoma-in-situ (CIS) with or without papillary component, any T1, or Ta high-grade lesions, will be enrolled. Pts must have urothelial carcinoma as the predominant histological component ( > 50%). Key exclusion criteria include locally advanced or metastatic BC, upper urinary tract disease within 2 years, prostatic urethral disease within 1 year, and prior immunotherapy. Using a novel adaptive-type design, pts will be randomized to 1 of 4 tx arms with NIVO ± linrodostat ± BCG. Primary endpoints include proportion of pts with CIS with complete response (CR) and duration of CR in pts with CIS. Secondary endpoints are progression-free survival and safety. This global study in 14 countries is underway, with a target enrollment of 436 pts. Clinical trial information: NCT03519256 .
A phase III randomized, placebo-controlled, double-blind study of niraparib plus abiraterone acetate and prednisone versus abiraterone acetate and prednisone in patients with metastatic prostate cancer (MAGNITUDE).
Authors: Chi Kim N. , Rathkopf Dana E. , Attard Gerhardt , Smith Matthew Raymond , Efstathiou Eleni , Olmos David , Small Eric Jay , Lee Ji Youl , Ricci Deborah S. , Simon Jason S. , Zhao Xin , Kothari Nishi , Cheng Shinta , Sandhu Shahneen Kaur 
Published: May 2020

TPS5588 Background: Preclinical data suggest synergistic antitumor activity when the PARP inhibitor (PARPi) niraparib is combined with the androgen pathway inhibitor abiraterone acetate1. The addition of a PARPi to abiraterone acetate plus prednisone (AAP) showed improved radiographic progression-free survival (rPFS) vs AAP alone in patients with mCRPC regardless of DNA repair gene defect (DRD) status2. Interim results from a phase I study support safety and tolerability of niraparib 200 mg combined with AAP in patients with mCRPC3. The objective of this Phase III study is to compare the efficacy and safety of niraparib plus AAP versus AAP with placebo as first-line therapy for mCRPC. Methods: This ongoing multicenter MAGNITUDE study (NCT03748641) will open in approximately 300 sites across 28 countries and will enroll patients with mCRPC who have not received treatment in the metastatic castrate resistant setting other than ongoing androgen deprivation therapy [ADT] and ≤4 months of AAP. DRD status will be determined by plasma and tissue assays. The cohort with DRD (n=400) and the cohort without DRD (n=600) will each be randomized 1:1 to niraparib + AAP or placebo + AAP. The first patient was consented in February 2019 and enrollment is ongoing. The primary objective of the study is to compare radiographic progression-free survival (rPFS) as assessed by blinded independent central radiology review in each cohort and treatment group. To test superiority of the combination vs AAP, sample sizes were estimated to provide 92% power to detect HR≤0.65 rPFS in the cohort with DRD and 94% power to detect HR≤0.67 in rPFS in the cohort without DRD, both at a 2-tailed level of significance of 0.05. The secondary objectives are time to symptomatic progression, time to cytotoxic chemotherapy, and overall survival. Safety and pharmacokinetic profiles will be evaluated. 1Rajendra N, et al. Cancer Res 2019;79(13 Suppl):Abstract nr 2134. 2Clarke N, et al. Lancet Oncol. 2018;(7):975-986. 3Saad, et al. Ann Oncol, 2018;29 (suppl 8), mdy284.043, https://doi.org/10.1093/annonc/mdy284.043 ) Clinical trial information: NCT03748641 .
DAROL: DARolutamide ObservationaL study patients in nonmetastatic castration-resistant prostate cancer (nmCRPC) patients.
Authors: Yu Evan Y. , Pieczonka Christopher Michael , Briganti Alberto , Murphy Declan G. , Lebret Thierry , Luz Murilo , Suzuki Hiroyoshi , Thiery-Vuillemin Antoine , Ortiz Jorge A. , Guan Rongjin , Armstrong Andrew J. 
Published: May 2020

TPS5593 Background: Patients (pts) with prostate cancer treated with prolonged androgen deprivation therapy (ADT) will eventually develop castration-resistant disease. Treatment of pts with nmCRPC with darolutamide (DARO) delays the development of metastases, which are associated with cancer-related morbidity. DARO is a structurally unique oral androgen receptor inhibitor approved by the FDA for the treatment of nmCRPC, based on prolonged metastasis-free survival (MFS) compared with placebo (median 40.4 months vs.18.4 months, respectively) in the ARAMIS phase III clinical trial. DARO showed a similar incidence of adverse events (AEs) compared to ADT alone and has a low potential for drug-drug interactions. However, phase III clinical trials cannot fully reflect all the facets of real-world pts. Therefore, non-interventional studies in the real-world setting, such as DAROL, are able to provide additional insight into the patterns of use and real-world safety profile of recently approved drugs. Methods: (NCT04122976) will enrol participants in the US, Brazil, Japan, and the EU. Eligible pts include men with histologically confirmed nmCRPC aged ≥18 yrs, life expectancy ≥3 months, and initiated on DARO treatment as per investigators’ decision within 3 days prior to enrollment. DAROL opened for enrollment in December 2019 in the US with a projected enrollment of 1000 pts. The primary endpoint of DAROL is safety. Treatment-emergent AEs will be collected during the study. Secondary endpoints to measure clinical effectiveness are MFS, time to symptomatic skeletal event, time to prostate-specific antigen progression, survival rate, and duration of DARO therapy. Other endpoints include pt demographics and characteristics, and prior and subsequent therapy. The estimated primary completion date is December 30, 2024. Clinical trial information: NCT04122976 .
A phase III trial of docetaxel versus docetaxel and radium-223 (Ra-223) in patients with metastatic castration-resistant prostate cancer (mCRPC): DORA.
Authors: Morris Michael J. , De Wit Ronald , Vogelzang Nicholas J. , Tagawa Scott T. , Higano Celestia S. 
Published: May 2020

TPS5594 Background: Ra-223, a bone-targeted alpha therapy, prolongs survival in patients (pts) with symptomatic mCRPC to bone. Docetaxel targets microtubule trafficking improving survival in the mCRPC and metastatic hormone-sensitive settings. We hypothesized that simultaneously targeting the tumor and bone compartment yields superior outcomes than targeting either alone. We previously determined the dose and schedule of co-administering Ra-223 + docetaxel in a randomized phase I/IIa trial. The combination appeared to have improved declines in prostate specific antigen (PSA) and bone markers, delayed PSA progression, and was better tolerated (with adjusted dose/schedule) relative to standard docetaxel alone. We are now conducting a phase III study to determine the clinical benefit of the regimen. Methods: Randomization (1:1) of 738 men with mCRPC to docetaxel or docetaxel + Ra-223 is planned with a projected hazard ratio for treatment effect (15 vs 20 months median survival) of 0.75. Pts with ≥2 bone lesions and progression by Prostate Cancer Working Group 3 criteria are eligible. Other key inclusion criteria are an Eastern Cooperative Oncology Group performance status of 0-1 and normal organ function. Key exclusion criteria are: use of anticancer therapy ≤4 weeks (wks) before randomization and use of bone-seeking radiopharmaceuticals or chemotherapy in the castration-resistant setting, and bulky visceral metastases (≥3 lung and/or liver or a lesion ≥2 cm in the previous 8 wks). Subjects receive docetaxel 75 mg/m2 IV q3w for 10 doses or docetaxel 60 mg/m2 IV q3w for 10 doses + Ra-223 55 kBq/kg IV q6w for 6 doses. The primary endpoint is overall survival. Secondary and exploratory endpoints include: radiographic progression-free survival, symptomatic skeletal event-free survival, safety, markers of bone metabolism, alterations in circulating tumor cells and DNA, detection of androgen-receptor splice variant 7, changes in automated bone scan index (aBSI), and assessment of patient-reported outcome instruments (FACT-P, Brief Pain Inventory, Brief Fatigue Inventory). The study is open at 25 sites in the US and Netherlands, sponsored by Memorial Sloan Kettering Cancer Center, and managed by the Prostate Cancer Clinical Trials Consortium. Clinical trial information: NCT03574571 .
A phase II study of M6620 in combination with carboplatin compared with docetaxel in combination with carboplatin in metastatic castration-resistant prostate cancer.
Authors: Choudhury Atish Dipankar , Xie Wanling , Parikh Mamta , Lee Daniel , Kessler Elizabeth R , Einstein David Johnson , Kochupurakkal Bose , Mouw Kent William , Van Allen Eliezer Mendel , Doyle L. Austin , D'Andrea Alan D. , Taplin Mary-Ellen , Shapiro Geoffrey 
Published: May 2020

TPS5597 Background: Alterations in DNA damage repair genes are common in metastatic castration-resistant prostate cancer (mCRPC), and are implicated in responses to carboplatin, PARP inhibitors and immunotherapeutics. The ATR kinase is involved in the DNA damage response, and ATR inhibitors have been demonstrated in preclinical models to have synergistic activity with platinum compounds due to induction of replication stress. Methods: This is a randomized open-label Phase 2 study of the ATR inhibitor M6620 + carboplatin vs. docetaxel + carboplatin in mCRPC. Patients (pts) previously treated with at least one secondary hormonal therapy and taxane-based chemotherapy undergo mandatory pre-treatment biopsy and are randomized 1:1 to receive Arm A (docetaxel 60 mg/m2 day 1 + carboplatin AUC 4 day 1) or Arm B (M6620 90 mg/m2 days 2,9 + carboplatin AUC 5 day 1) every 21 days. Pts randomized to Arm A who are not candidates for docetaxel receive carboplatin AUC 5 monotherapy. Stratification factors are 1) prior PARP inhibitor (yes vs. no) and 2) evaluable disease by RECIST 1.1 (yes vs. no). Pts on Arm A crossover to Arm B (M6620+carboplatin) at the earlier of PSA or radiographic progression. For the primary endpoint of overall response rate (ORR; PSA reduction by ≥ 50% or radiographic response by RECIST 1.1), with 65 pts on each arm (total N = 130), there will be 80% power to distinguish ORR of 40% vs. 20% using a chi-square test (one sided α = 0.05). 136 pts will be enrolled to account for 5% dropout. Secondary endpoints include time to PSA progression, radiographic PFS, PFS by PCWG3 criteria, safety and adverse events in each arm. Biomarker studies include whole exome sequencing, RAD51 focus formation, and ATM IHC from tumor specimens. Circulating cell-free DNA from pre-treatment and progression plasma specimens will undergo ultra-low pass whole genome sequencing and deep targeted sequencing. The goal of this study is to expand therapeutic options in mCRPC through a novel approach to targeting the DNA damage response, and to identify biomarkers associating with response and resistance to both standard and trial therapy. Enrollment began June 2019 (NCI/ETCTN #10191, NCT03517969). Clinical trial information: NCT03517969 .