bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 1b/2 dose expansion, open-label study to evaluate safety and anti-tumor activity of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer.
Authors: Sun Wei , Bandari Jathin , Zummo Jacqueline , Belani Khushboo , Brown Eppie , DiFiglia Andrea , Metcalf McKenna , Nanayakkara Nuwan 
Published: June 2023

TPS4618 Background: Bladder cancer is the most common malignancy involving the urinary system, with over 700,000 individuals living with bladder cancer in the US in 2019. In the US, approximately 80,000 new cases and 18,000 deaths occur each year due to bladder cancer. Approximately 70% of new urothelial bladder cancer cases are classified as non-muscle invasive bladder cancer (NMIBC). With the current Bacillus Calmette-Guerin (BCG) shortage and limited effective alternate therapies, there continues to be a significant unmet need for treatment options for patients with NMIBC. TARA-002 is being developed for intravesical instillation for the treatment of high-grade (HG) NMIBC. TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin. The chemical characteristics of TARA-002 are intended to be comparable to OK-432. Therefore, nonclinical and clinical evidence with OK-432 and TARA-002 support the ADVANCED-1 study (dose escalation Phase 1a [NCT05085977] and dose expansion Phase 1b/2 [NCT05085990]). The dose for the planned Phase 1b/2 study (ADVANCED-1-Ph1b/2) will be based on the recommended Phase 2 dose (RP2D) established in the Phase 1a study. Methods: ADVANCED-1-Ph1b/2 is a Phase 1b/2, dose expansion, open-label study of intravesical instillation of TARA-002 in adults with HG carcinoma in situ (CIS) NMIBC. The purpose of this study is to evaluate the safety and anti-tumor activity of TARA-002 administered intravesically for the treatment of subjects with CIS NMIBC (± Ta/T1) with active disease. The study includes approximately 102 eligible male and female subjects ≥ 18 years of age enrolled in 2 cohorts based on their prior BCG experience. Cohort A includes subjects unable to obtain BCG or subjects who have not received BCG in the last 24 months prior to CIS diagnosis, and Cohort B includes subjects with CIS who are BCG unresponsive after completion of adequate BCG therapy (at least 5 of 6 doses of an initial induction course plus either at least 2 of 3 doses of maintenance therapy or at least 2 of 6 doses of a second induction course). Those with current or a history of penicillin allergy or current evidence of any condition, therapy, or laboratory abnormality that might confound the results are excluded. The overall study duration is 6 months/24 weeks per subject for Ph1b/2-Cohort A (includes induction, reinduction [if applicable]), and 24 months/96 weeks per subject for Ph1b/2-Cohort B (includes induction, reinduction [if applicable], maintenance until 18 months). The ADVANCED-1 study started in March 2022. Phase 1a is open for enrollment. Phase 1b/2 is expected to begin enrollment in May 2023. Clinical trial information: NCT05085977 ; NCT05085990 .
GUIDE: A randomized non-comparative phase II trial of biomarker-driven intermittent docetaxel versus standard-of-care docetaxel in metastatic castration-resistant prostate cancer (ANZUP 1903).
Authors: Conduit Ciara , Mak Blossom , Qu Wenjia , Yeung Theresa , Bressel Mathias , Cusick Thomas , Dhillon Haryana M. , De Abreu Lourenço Richard , Underhill Craig , Torres Javier , Crumbaker Megan , Honeyball Florian , Linton Anthony , Sewak Sanjeev , Chau Nguyen Minh Hieu , Allen Ray , Davis Ian D. , Clark Susan J. , Horvath Lisa , Mahon Kate Lynette ,   The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: June 2023

TPS5099 Background: Docetaxel improves survival in people with metastatic castration resistant prostate cancer (CRPC) but is associated with toxicities which impact tolerability, particularly for patients who may be older and often with multiple co-morbidities. Biomarker-driven de-escalation of docetaxel chemotherapy may allow improved balance of cancer control and quality of life against toxicity. In patients with metastatic CRPC receiving docetaxel, a reduction to undetectable levels in circulating promoter methylated glutathione S-transferase Pi-1 ( mGSTP1) DNA after 2 cycles of chemotherapy is associated with improved overall survival1. This study aims to determine the efficacy and safety of intermittent docetaxel chemotherapy guided by the presence or absence of circulating mGSTP1 DNA in patients with metastatic CRPC. Methods: GUIDE (NCT04918810) is a randomized, two-arm, non-comparative phase 2 trial recruiting 120 patients at eight Australian centres. Patients with Prostate Cancer Working Group-3 defined metastatic CRPC who are commencing docetaxel 75mg/m2 q3w will be pre-screened for detectable mGSTP1 at baseline +/- following two cycles of treatment. Those with detectable plasma mGSTP1 at baseline that becomes undetectable after two cycles of chemotherapy will be eligible for GUIDE. Prior to Cycle 4 of docetaxel, these patients are randomized 2:1 to one of two treatment arms: Arm A (cease docetaxel and reinstitute if mGSTP1 becomes detectable) or Arm B (continue docetaxel 75mg/m2 q3w in accordance with clinician’s usual practice) (Figure 1). The primary endpoint is radiographic progression-free survival (rPFS). Secondary endpoints include time on treatment holidays, safety, patient-reported outcomes, overall survival, health resource use and cost associated with treatment. This study is powered to detect a rPFS curve with at least 50% rPFS at 12 months using a one-sided log-rank test with 2.5% alpha and 90% power. 3 of planned 120 patients have been enrolled. This novel study is the first to prospectively test the clinical utility of a circulating epigenetic biomarker ( mGSTP1) in clinical decision-making in prostate cancer, building upon existing data supporting analytical and clinical validity. We anticipate that this novel biomarker will safely guide treatment de-escalation and improve the quality of survival for a group of patients with metastatic CRPC. Clinical trial information: NCT04918810 .
A study of prospective monitoring of patients with recurrent prostate cancer using serial PSMA imaging (18F-DCFPyL).
Authors: Atiq Mohammad O. , Lindenberg Liza , Mena Gonzalez Esther , Turkbey Baris , Karzai Fatima , Hausler Megan , Cordes Lisa M. , Williams Monique , Hankin Amy , Gulley James L. , Figg William Douglas , Choyke Peter L. , Madan Ravi Amrit 
Published: June 2023

TPS5101 Background: 18F-DCFPyL PSMA PET imaging is now FDA approved for patients with high-risk prostate cancer and those with biochemically recurrent prostate cancer (BCR). BCR has been traditionally defined as a rising PSA after definitive surgery and/or radiation have not been curative in patients without tumor findings on a CT or Tc99 bone scan. There are an estimated 25,000-50,000 new cases of BCR in the US annually. BCR patients are usually managed conservatively, often with surveillance since there is no data demonstrating interventions improve survival. Although 18F-DCFPyL will be able to detect disease at the micrometastatic/subclinical level, there is limited prospective data on how these patients should be managed. While great enthusiasm exists to utilize radiation or ADT-based regimens extrapolated from a more advanced disease state, the natural history of subclinical disease seen on 18F-DCFPyL remains unclear (Madan RA et al. J Clin Oncol 2022). Methods: The primary objective of this study is to monitor patients with recurrent prostate cancer to learn about the natural history of 18F-DCFPyL PET positive disease in this patient population. Eligible patients include those who have had prior definitive surgery or radiation, current PSA ≥0.50 ng/mL, testosterone > 100 ng/mL, no evidence of soft tissue disease on CT scan/MRI and no bone lesions on bone scan. Patients will undergo initial imaging with 18F-DCFPyL scans. Those with negative findings on the initial scan will have annual repeat 18F-DCFPyL scans. Patients with positive initial scans will be scanned every 6 months. All patients will have PSA testing every 3 months and will undergo annual CT and Tc99 bone scans. Up to 250 patients will be followed for 5 years or until off-study criteria is met (including new findings on CT/bone scans consistent with metastatic disease or continuous systemic prostate cancer therapy for more than 6 months). In addition to monitoring the imaging changes, we will evaluate patterns of progression on 18F-DCPyL scans over time, analyze PSA doubling time in context of 18F-DCFPyL changes and evaluate circulating biomarkers. ClinicalTrials.gov Identifier: NCT05588128. Clinical trial information: NCT05588128 .
First-in-class oral innate immune activator BXCL701 combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of small cell neuroendocrine (SCNC) variant: Randomized phase 2b trial.
Authors: Aggarwal Rahul Raj , Zhang Jingsong , Monk Paul , Zhu Xinhua , Costin Dan , Petrylak Daniel P. , Borderies Pascal , Deshpande Rashmi Majali , Hafeez Amir , O'Neill Vincent J. , Tagawa Scott T. 
Published: June 2023

TPS5109 Background: BXCL701 (talabostat), oral small molecule inhibitor of dipeptidyl peptidases (DPP)—primarily DPP8/9 & DPP4—triggers inflammasome to alert and prime immune cells, leading to induction of IL-18 & IL-1ß, bridging innate & adaptive immunity. BXCL701 + pembrolizumab evaluated in a Phase 2 study, in mCRPC patients with SCNC. SCNC is highly proliferative and aggressive with limited duration of response to platinum-based chemotherapy. Final results of Phase 2a presented at ASCO GU 2023 (abstract #176) after enrollment of 28 evaluable SCNC patients. 7 (25%) patients achieved a composite response, primary endpoint of trial. In patients with measurable disease (n = 25), RECIST 1.1-defined partial response (PR) observed in 5 (20%) patients (4 confirmed PR + 1 uPR). Disease control rate (complete response + PR + stable disease) was 48% (12 patients). Median duration of response for both composite responses and RECIST-defined PRs was 6+ months as of data cutoff on 19-DEC-22. 6 / 34 patients (18%) in safety population experienced serious adverse events (SAEs) possibly related to BXCL701 or pembrolizumab, and 6 (18%) patients discontinued any drug due to an AE. No evidence found that BXCL701 potentiates immune-related AEs related to immune checkpoint inhibitors. DPP9 overexpression was identified as a potential predictive biomarker for BXCL701 response; biomarker evaluation is ongoing and additional findings will be presented at an upcoming medical meeting. Since SCNC cohort showed encouraging efficacy in Phase 2a, the Phase 2b portion of study was initiated to evaluate SCNC variant in a potential registrational randomized study. Methods: Patients with any SCNC histopathological features, either de novo or treatment-emergent including mixed SCNC, are randomized 2:1 to receive BXCL701 + pembrolizumab (n = 40) or BXCL701 monotherapy (n = 20). Patients are required to have progression by PCWG3 on ≥1 prior line of cytotoxic chemotherapy (patients who either have refused chemotherapy or are considered unsuitable for chemotherapy also permitted entry with prior approval by sponsor). Patients receive pembrolizumab (200 mg IV q3week Day 1) + BXCL701 or BXCL 701 alone (0.2 mg BID Days 1-7 with step-up to 0.3 mg BID Days 8-14, and 0.3 mg BID Days 1-14 of subsequent 21-day cycles). Primary endpoint is response rate defined by RECIST 1.1 criteria. Secondary objectives are ≥-50% decline in PSA from baseline, OS, duration of response, rPFS, and PSA PFS. Exploratory biomarkers and changes in relevant immune effector cells are also evaluated. Phase 2a activity threshold for accrual was met. ClinicalTrials.gov Identifier: NCT03910660. Clinical trial information: NCT03910660 .
APPROACH trial: Multimodal approach in patients with mHSPC: A pragmatic, randomized, phase 3 trial of androgen-deprivation therapy (ADT) plus apalutamide (APA) versus ADT plus apalutamide (APA) and local treatment—Meet-URO 29 study.
Authors: Guadalupi Valentina , Rametta Alessandro , Verzoni Elena , Claps Melanie , Sepe Pierangela , Stellato Marco , Bottiglieri Achille , Catanzaro Mario , Avuzzi Barbara , Sighinolfi Maria Chiara , Rocco Bernardo , Jereczek Barbara , Di Maio Massimo , Nicolai Nicola , De Braud Filippo G. , Procopio Giuseppe 
Published: June 2023

TPS5115 Background: it is reasonable to offer radiotherapy (RT) to improve outcomes for patients with newly diagnosed M1 prostate cancer with < 5 bone metastases (HORRAD) or low volume disease (STAMPEDE) (Burdett, S et al., Eur. Urol. 2019). Data from clinical randomized trials evaluating feasibility and overall benefit of cytoreductive radical prostatectomy (cRP) in oligometastatic ormone sensitive patients are not available. The rationale for performing cytoreductive radical prostatectomy is to eliminate lethal clones ofcastration-resistant intraprostatic PCa, which can favor the process of metastasis (A Heidenreich et al. Current Opinion in Urology 2020), in order to improve OS and PFS and to prevent local progression and correlated events. Methods: APPROACH is an Italian multicenter study, which is enrolling ~566 pts with oligometastatic hormone sensitive prostate cancer who are candidates to receive treatment with apalutamide. After 6 months from the start of treatment, patients will be randomized 1:1 to receive local treatment or not in addition to apalutamide (investigator's choice between primary radiotherapy and cytoreductive prostatectomy). Primary end point: To determine whether treatment with apalutamide plus ADT for 6 months followed by locoregional treatment with radiotherapy or radical prostatectomy has better efficacy than treatment with apalutamide plus ADT alone in terms of radiographic progression-free survival (rPFS). Secondary end points: To evaluate tumor shrinkage after locoregional approach and to evaluate short and long-term side effects after locoregional surgery or RT, time to PSA progression, time to castration resistance, cancer specific survival, overall survival and quality of life according to EPIC-26 and EQ-5D-5L questionnaires. Clinical trial information: NCT05649943 .
PSMAddition: A phase 3 trial to compare treatment with 177Lu-PSMA-617 plus standard of care (SoC) and SoC alone in patients with metastatic hormone-sensitive prostate cancer.
Authors: Tagawa Scott T. , Sartor A. Oliver , Saad Fred , Reid Alison Helen , Sakharova Olga V. , Feng Felix Y , Fizazi Karim , Morris Michael J. 
Published: June 2023

TPS5116 Background: Lutetium (177Lu) vipivotide tetraxetan (177Lu-PSMA-617) plus protocol-permitted standard of care (SoC) significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer, previously treated with at least one androgen receptor pathway inhibitor (ARPI) and one or two taxanes. Androgen deprivation therapy (ADT) and ARPIs may alter PSMA expression and radiosensitivity. PSMAddition will assess the efficacy and safety of 177Lu-PSMA-617 plus SoC versus SoC alone in adults with metastatic hormone-sensitive prostate cancer (mHSPC). Methods: PSMAddition (NCT04720157) is an international, prospective, open-label, randomized, phase 3 trial, with crossover, in adults with mHSPC. Eligible patients are treatment-naive or minimally treated candidates for hormonal therapy, with PSMA-positive disease (determined by 68Ga-PSMA-11 PET/CT), ECOG performance status of 0 to 2 and adequate major organ function. Patients are excluded if they have rapidly progressing tumors that require chemotherapy. Approximately 1126 patients will be randomized 1:1 to receive 177Lu-PSMA-617 (7.4 GBq every 6 weeks for a maximum of 6 cycles) plus SoC or SoC alone (an ARPI and ADT). Stratification factors are tumor volume (high/low), age (≥ 70/ < 70 years), and previous/planned prostatectomy or radiation treatment of the primary prostate tumor (yes/no). Recruitment for a China extension cohort (40–60 patients) will follow after completion of main study recruitment. The primary endpoint is rPFS, as assessed by blinded independent centralized review. Upon centrally confirmed radiographic progression, participants in the SoC-only arm can cross over to the 177Lu-PSMA-617 arm. The planned sample size provides 95% power to detect a hazard ratio of 0.7 for rPFS after 418 events with an overall one-sided significance level of 0.025. The key secondary endpoint is OS, others include the proportion of patients with a prostate-specific antigen (PSA) decline of ≥ 90% from baseline, time to development of metastatic castration-resistant prostate cancer, composite PFS (radiographic, clinical or PSA progression), safety and tolerability, and health-related quality of life. Imaging and biospecimen (tissue and blood) collection is embedded for correlative analysis. Participants who have received 177Lu-PSMA-617 will have the option to enroll in a separate long-term safety follow-up study. Updated from previous presentation at the 2021 European Society for Medical Oncology Congress, FPN 3035, with permission. Clinical trial information: NCT04720157 .
UPGRADE-A: Phase 1 expansion trial of the NaPi2b-directed antibody drug conjugate (ADC) upifitamab rilsodotin (UpRi) in combination with carboplatin in patients with high-grade serous ovarian cancer (HGSOC).
Authors: Hays John L. , Friedman Claire Frances , Lakhani Nehal , Anderson Charles K , Buscema Joseph , Duska Linda R. , Hamilton Erika P. , Taylor Sarah E. , Carrington Cassandra , Burger Robert Allen , Werner Theresa Louise 
Published: June 2023

TPS5613 Background: UpRi is a first in class NaPi2b ADC with a novel scaffold-linker-payload that is designed to enable high drug-to-antibody ratio and controlled bystander effect. NaPi2b is a sodium-dependent phosphate transporter protein broadly expressed in HGSOC, with limited expression in healthy tissues. Interim data from a previous phase 1b study of heavily pretreated HGSOC patients reported clinical activity and tolerability data for UpRi as a monotherapy, most notably in patients with NaPi2b positive tumors (TPS≥75). Based on these emerging single-agent safety and efficacy data, it is hypothesized that UpRi in combination with carboplatin may provide additional clinical benefit for patients in earlier lines of treatment. UPGRADE-A is a Phase 1 dose escalation (DES) and expansion (EXP) study to evaluate UpRi and carboplatin followed by UpRi maintenance in recurrent platinum-sensitive HGSOC. The DES portion of UPGRADE-A has completed enrollment, and the EXP portion is ongoing. Methods: The EXP cohort of UPGRADE-A is enrolling patients with recurrent or metastatic PSOC (defined as having achieved a PR or CR to 4+ cycles in their last platinum containing regimen) who have received 1-3 prior lines of therapy. Up to 1 non-platinum based prior chemotherapy regimen is allowed, provided it is not the most recent line of chemotherapy. The primary objective of EXP is feasibility of UpRi + carboplatin at the RP2D, defined as 60% of patients completing at least 4 cycles of UpRi + carboplatin without discontinuing treatment early for reasons other than disease progression. Secondary objectives include the safety/tolerability, pharmacokinetics, and preliminary anti-neoplastic activity of the UpRi + carboplatin combination. Tumor tissue must be provided (archival or fresh sample) for retrospective NaPi2b assessment. UpRi 30mg/m2 + carboplatin (AUC 5) will be administered IV every 28 days for up to 6 cycles, followed by UpRi maintenance monotherapy until disease progression or unacceptable toxicity. Up to 30 patients are expected to enroll in EXP, and the trial is currently open for enrollment. NCT04907968. Clinical trial information: NCT04907968 .
A randomized trial of olaparib, durvalumab, and cancer vaccine, UV1, as maintenance therapy in patients with BRCAwt with recurrent ovarian cancer: ENGOT-OV56/NSGO-CTU-DOVACC trial.
Authors: Mirza Mansoor Raza , Pietzner Klaus , Van Nieuwenhuysen Els , Marth Christian , Boere Ingrid , Lindemann Kristina , Fernebro Josefin , Hietanen Sakari , Brasiuniene Birute , Pors Kirsten , Gybel Frederiksen Signe , Ji Mee Willerslev Ulrikke , Braicu Elena Ioana , Madsen Kristine , Zagouri Flora 
Published: June 2023

TPS5615 Background: Most ovarian cancers (OC) are diagnosed at an advanced stage and despite initial therapy, the disease will often relapse and require further treatment Thus, there is a need for novel therapeutic options. PARP inhibitors lead to increasing tumour neoantigen, and modulation of the tumour microenvironment, which may facilitate a more profound antitumour immune response. UV1 is a therapeutic cancer vaccine directed against telomerase. Since telomerase is an essential enzyme and universally expressed by most tumor cells, it represents a unique cancer antigen as a basis for immunotherapy (IO). The rationale for integrating immunotherapy as maintenance therapy following chemotherapy is based on preclinical studies which have shown that chemotherapy induces immunogenic cell death leading to increased recognition of the tumor by the immune system. The proposed study is evaluating the use of the therapeutic cancer vaccine UV1 in combination with olaparib and the PD-L1 inhibitor, durvalumab as maintenance therapy after response to platinum-based chemotherapy. Methods: The primary objective is to demonstrate efficacy of UV1-olaparib-durvalumab combination maintenance therapy against olaparib in maintenance after platinum combination therapy for BRCAwt patients with relapsed ovarian cancer. Key eligibility criteria include: histologically confirmed, platinim sensitive recurrent OC in response to last platinum-containing chemotherapy, BRCAwt. Patients may be previously treated with PARPi, however prior IO is not permitted. Patients are stratified by HRD status and previous use of PARPi. 184 patients are randomized to three arms (1:1:2): arm A: olaparib single agent, arm B: olaparib-durvalumab and arm C: olaparib, durvalumab-UV1. Duration of therapy: olaparib until progression of disease; durvalumab for 24 months; intradermal UV1, 8 doses within 5 months. Intradermal sargramostim is used as vaccine adjuvant. Primary endpoint is progression-free survival (PFS) of arm C versus arm A. Key secondary endpoints include PFS arm B versus C, patient reported outcomes, and overall survival. This NSGO-CTU sponsored trial is enrolling patients in 11 countries. The following cooperative groups are participating: NSGO-CTU (DK, FIN, NOR, SWE, LTU), BGOG (BE), HeGOG (GRC, CYP), NOGGO (DE), AGO-A (AUT) & DGOG (NL). Clinical trial information: NCT04742075 .