bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAMETA: An open-label, three-arm, multicenter, phase III study of savolitinib + durvalumab versus sunitinib and durvalumab monotherapy in patients with MET-driven, unresectable, locally advanced/metastatic papillary renal cell carcinoma (PRCC).
Authors: Choueiri Toni K. , Xu Wanning , Poole Lynne , Telaranta-Keerie Aino , Hartmaier Ryan , Powles Thomas 
Published: June 2022

TPS4601 Background: Papillary renal cell carcinoma (PRCC) is the most common subtype of non-clear cell RCC and accounts for 10–15% of RCCs. Approximately 80% of PRCC cases are MET-driven, characterized by genomic abnormalities resulting in dysregulation of the MET signaling pathway, making these abnormalities a potential therapeutic target for treatment. Savolitinib is an oral, potent and highly selective MET tyrosine-kinase inhibitor (TKI) demonstrating preliminary clinical activity in advanced solid tumors, including in MET-driven PRCC, defined as presence of any of the following molecular alterations, in the absence of co-occurring fumarate hydratase mutations: chromosome 7 gain, MET amplification, MET kinase domain variations, or hepatocyte growth factor amplification. In the Phase III SAVOIR study, in PRCC, savolitinib monotherapy showed encouraging efficacy vs the multi-targeted TKI, sunitinib. In addition, non-clinical studies suggest a possible synergistic anti-tumor effect of MET-inhibitors and programmed cell death-ligand (PD-L1) inhibitors, such as durvalumab; emerging data from the Phase I/II CALYPSO study investigating savolitinib plus durvalumab shows a notable efficacy signal in patients with MET-driven PRCC. Following these findings, the SAMETA study (NCT05043090) is designed to evaluate the efficacy and safety of savolitinib in combination with durvalumab vs sunitinib and durvalumab monotherapy in PRCC. Methods: In this open-label, three-arm, multi-center, Phase III study, adult patients with unresectable, MET-driven and locally advanced/metastatic PRCC are eligible. An estimated 200 patients (25 countries, 165 centers) will be randomized in a 2:1:1 ratio into three treatment arms (A–C) with stratification by International metastatic RCC database consortium risk group & PD-L1 expression tumor status. Arm A: oral savolitinib 600 mg once daily (QD) plus intravenous (IV) durvalumab 1500 mg every 4 weeks (Q4W); Arm B: oral sunitinib 50 mg QD for 4 consecutive weeks, followed by a sunitinib-free interval of 2 weeks Q6W; Arm C: IV durvalumab 1500 mg Q4W. Study treatment continues until RECIST 1.1 disease progression or another discontinuation criterion is met. The primary endpoint is progression-free survival (by BICR; RECIST v1.1). Secondary endpoints include overall survival, objective response rate and duration of response. Safety (adverse events, vital signs, ECG, hematology and biochemistry parameters) will also be reported. The first patient was enrolled onto the study on 28 October 2021. Clinical trial information: NCT05043090.
A phase III randomized trial of eribulin (E) with or without gemcitabine versus standard of care (SOC) for metastatic urothelial carcinoma (UC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937.
Authors: Sadeghi Sarmad , Plets Melissa , Lara Primo "Lucky" N. , Tangen Catherine , Bangs Rick , Lerner Seth P. , Flaig Thomas W. , Petrylak Daniel P. , Thompson Ian 
Published: June 2022

TPS4608 Background: UC is 2nd most common genitourinary cancer. Current SOC offers platinum-based (PB) first line chemotherapy (chemo) with ddMVAC or gemcitabine-cisplatin (GC) regimens. For cisplatin ineligible patients (pts), SOC includes gemcitabine-carboplatin (GCa), and in select pts pembrolizumab. Erdafitinib is approved for pts with FGFR alterations and Enfortumab vedotin (EV) is approved for previously treated pts. A phase I/II CTEP study of eribulin (E) for metastatic UC (mUC) established the activity of E in UC with objective response rate (ORR) of 37.5% and a median progression free survival (PFS) of 4.1 months (mo) and median overall survival (OS) of 9.5 mo (N = 150). A phase II CTEP study of gemcitabine-eribulin (GE) in cisplatin ineligible mUC showed an ORR of 50%, median OS of 11.9 mo and median PFS of 5.3 mo (N = 24). The most common Grade 3-4 toxicities included: neutropenia 63%, anemia and fatigue 29%. Pts with liver metastases benefited from therapy with 5 responders in 7 pts for GE vs 12 out 49 E. Methods: This is a phase III, randomized 3 arm study comparing E vs. GE vs. SOC (docetaxel, paclitaxel, or gemcitabine). E is given at 1.4mg/m2 on day (D) 1 and 8 of a 21 D cycle. In the GE arm, gemcitabine is added to E at 1000 mg/m2 dose to D1 and D8. SOC follows standard dosing of the agents. There is no limit to the number/sequence of prior regimens. A simplified summary of eligibility criteria is presented here. All pts must have: received frontline systemic treatment such as PB chemo or a non-platinum regimen. received PD1/PDL1 Ab or be deemed ineligible for PD1/PDL1 Ab. received EV. Assuming a median OS for the SOC arm of 7 mo the study seeks to find at least a 50% increase in median OS to 10.5 mo (Hazard Ratio (HR) = 0.667). One-sided 0.0125 type I error to account for testing of two primary hypotheses (Each arm vs. SOC). 87% power to detect a 3.5 mo improvement in OS. We require 140 eligible (155 total) pts in each arm for a total of 465. The study was activated in Feb 2021 and accrual is ongoing. Clinical trial information: NCT04579224.
89Zirconium-labelled girentuximab (89Zr-TLX250) PET in patients with urothelial cancer (ZiPUP): A phase I trial of a novel staging modality for urothelial carcinoma.
Authors: Hayne Dickon , Gauci Richard , Al-Zubaidi Mohammed , Viswambaram Pravin , McCombie Steve P , Liow Elizabeth Chien Hern , Lenzo Nat , Ferguson Thomas , Antonini Paola , Meyrick Danielle , Hayward Colin , Redfern Andrew David 
Published: June 2022

TPS4609 Background: Bladder cancer is a lethal disease with a rising incidence. The current standard imaging modalities for staging are either CT of the chest, abdomen and pelvis or FDG PET/CT. However, there are issues with using these modalities for staging. CT is known to have relatively low sensitivity for detecting low volume metastatic disease, while FDG is predominantly renally excreted and therefore has intense activity in the urinary tract, which limits its utility to detect bladder or upper tract lesions, or nodal metastases in close proximity to the urinary tract. Zirconium-89-Girentuximab (89Zr-TLX250) may have utility in the accurate staging of bladder and urothelial cancer, with less renal excretion as compared to FDG, however this has not previously been investigated. ZipUp is an investigator initiated trial. South Metropolitan Health Service WA is the trial sponsor. The study received funding and study drug support from Telix Pharmaceuticals Methods: ZiPUP is a single-arm, phase I trial examining the feasibility, safety, and utility of 89Zr-TLX250 PET/CT in patients either undergoing pre-operative staging of urothelial carcinoma or bladder cancer for curative intent, or with known metastatic urothelial carcinoma or bladder cancer. All participants will undergo 89Zr-TLX250 PET/CT and will need to have undergone recent FDG PET/CT for means of comparison. This trial aims to recruit 10 participants undergoing staging and 10 participants with known metastatic disease. The primary endpoint is effectiveness by assessing sensitivity and specificity in detecting lymph node metastases compared to FDG PET/CT; secondary endpoints are safety, tolerability, and feasibility. The first patient was enrolled in this single site study and the study is expected to be completed by December 2022. If 89Zr-TLX250 PET/CT is proven to be feasible, safe, and effective in staging urothelial cancer, it could improve the appropriate selection of treatment for patients with metastatic or primary urothelial carcinoma or bladder cancer. Clinical trial information: NCT05046665.
Trial in progress: A phase II switch maintenance study of live biotherapeutic MRx0518 and avelumab in patients with unresectable locally advanced or metastatic urothelial carcinoma (UC) who did not progress on first-line platinum-containing chemotherapy.
Authors: Shah Amishi Yogesh , Gao Jianjun , Rezazadeh Arash , Cole Suzanne , Jain Rohit K. , Stevenson Alex , Fyvie Gayle , Gaw Nina Jane , Pant Shubham 
Published: June 2022

TPS4610 Background: Efficacy of avelumab for maintenance treatment of UC was investigated in the JAVELIN Bladder 100 study (NCT02603432), which led to the FDA approval of avelumab for maintenance treatment as the current standard of care for patients with locally advanced or metastatic UC that have not progressed with first-line platinum-based chemotherapy. Outcomes included median overall survival (OS) of 21.4 months (95% CI 0.56-0.86), median progression-free survival (PFS) of 3.7 months (95% CI 3.5-5.5) and objective response rate (ORR) of 9.7% (95% CI 6.8-13). MRx0518 is a novel, human gut microbiome-derived, single-strain, live biotherapeutic. It is a bacterium of the Enterococcus genus that was selected for development in solid tumor treatment for its strong in vitro and in vivo immunostimulatory activity. In vivo studies have shown that MRx0518 can inhibit tumor growth in different syngeneic cancer models as both monotherapy and in combination with immune checkpoint inhibitors. MRx0518 has been shown to reduce Treg and increase Th1 and Tc1 lymphocyte differentiation in vitro and increase intratumoral CD4+ and CD8+ T cells and NK cells in vivo. In clinical studies, preliminary data shows that MRx0518 monotherapy can increase anti-tumor TILs and systemic pro-inflammatory immune signaling molecules. This is a pilot study evaluating whether the addition of MRx0518 to avelumab in the maintenance setting of metastatic platinum-treated UC may improve outcomes. Methods: The study will enroll 30 patients with unresectable locally advanced or metastatic UC at multiple US centers. Patients must have measurable disease after a partial response or stable disease on 4-6 cycles of platinum-containing induction chemotherapy. Patients will receive 800 mg avelumab IV infusion every 2 weeks in combination with 1 oral capsule (10x1010 – 10x1011 CFU) MRx0518 twice daily until disease progression, patient withdrawal or unacceptable toxicity. Primary objectives are to assess safety of the combination, and effect on PFS at 6 months. Secondary objectives are to assess other efficacy measures including PFS, ORR, OS, duration of response, time to response, and disease control rate. Collection of paired research biopsies at baseline (after chemotherapy) and on treatment (after 8 weeks of MRx0518 + avelumab), plus longitudinal blood sampling, will allow investigation of immunological changes systemically both in the tumor and as potential predictive markers of response. Stool and urine samples collected before, during and after treatment will allow investigation of changes to the microbiome and metabolome. Recruitment is open, awaiting accrual. Clinical trial information: NCT05107427.
A phase II study of gemcitabine plus cisplatin chemotherapy in patients with muscle-invasive bladder cancer with bladder preservation for those patients whose tumors harbor deleterious DNA damage response (DDR) gene alterations (Alliance A031701).
Authors: Iyer Gopa , Ballman Karla V. , Atherton Pamela J. , Murray Katie , Kwok Young , Steen Preston D. , Baghaie Shiva , Rosenberg Jonathan E. , Morris Michael J. 
Published: June 2022

TPS4615 Background: While a standard approach to muscle-invasive bladder cancer (MIBC) management involves neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC), up to 50% of pts recur with metastatic disease. Moreover, removal of the bladder has a significant impact on pts’ quality of life. Pathologic downstaging to non-muscle-invasive disease (<pT2) or complete response (pT0) at RC is associated with long-term survival benefit. Somatic DDR gene alterations were shown to be enriched in pts who were pT0 at RC following NAC in multiple retrospective analyses. We hypothesize that MIBC pts with somatic loss-of-function alterations within specific DDR genes and clinical responses to NAC can be uniquely managed with a bladder-sparing approach consisting of close cystoscopic and radiographic surveillance, avoiding the toxicities of definitive local therapy. Methods: A031701 is a multicenter phase II trial that will enroll 271 pts with T2-T4aN0/xM0 MIBC diagnosed within 60 days prior to enrollment. Multifocal MIBC, tumors >5 cm by cystoscopic assessment, and Bacillus Calmette-Guérin (BCG)-refractory disease (beyond standard induction and maintenance) are not allowed. Intravesical chemotherapy is allowed. Pts must be eligible for cisplatin chemotherapy. Eligible pts will receive either standard dose or dose dense gemcitabine and cisplatin chemotherapy (investigator’s choice) with simultaneous genetic sequencing of pre-treatment transurethral resection specimens. Pts whose tumors contain deleterious alterations in any 1 of 9 pre-selected DDR genes ( ERCC2, ERCC5, BRCA1, BRCA2, RECQL4, RAD51C, ATM, ATR, and FANCC) and who exhibit <T1 response on clinical restaging are eligible for organ-sparing management. Pts without deleterious DDR gene alterations or with >T1 disease after NAC will undergo RC or chemoradiation therapy (investigator/patient choice). The primary endpoint is 3-year event-free survival in DDR-altered pts who undergo bladder sparing, defined as the proportion of pts without BCG-unresponsive non-muscle invasive recurrences, any >T2 recurrences, or any metastatic recurrences. Secondary endpoints include clinical response rate (<cT1) in patients with deleterious DDR gene alterations following NAC, bladder-intact survival, overall survival, pT0 rate in DDR-altered pts who elect to undergo RC, pT0 rate in pts without DDR gene alterations, 3-year RC rate in pts with DDR gene alterations, and proportion of pts undergoing intravesical management for in-bladder recurrences. The study opened for enrollment in September 2018. Support: U10CA180821, U10CA180882. Clinical trial information: NCT03609216.
Phase 1b study of bavdegalutamide, an androgen receptor PROTACdegrader, combined with abiraterone in patients with metastatic prostate cancer.
Authors: Shore Neal D. , Shen John , Devitt Michael Edward , Lu Haolan , Alicea Jeanette , Parameswaran Janaki , Chirnomas Deborah , Gao Xin , McKean Meredith 
Published: June 2022

TPS5106 Background: Bavdegalutamide (ARV-110) is a novel, oral PROteolysis TArgeting Chimera (PROTAC) protein degrader that targets wild-type androgen receptor (AR) and clinically relevant mutants. Bavdegalutamide demonstrated tumor growth inhibition in multiple xenograft models (eg, AR gene amplification, AR mutation, enzalutamide resistance, and enzalutamide insensitivity). In a phase 1/2 study (NCT03888612), bavdegalutamide showed clinical activity in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received 1–2 prior novel hormonal agents (eg, abiraterone and/or enzalutamide), including heavily pretreated patients. Abiraterone is approved, in combination with a corticosteroid, to treat patients with mCRPC or with high-risk castration-sensitive prostate cancer (CSPC). Up to a third of patients treated with abiraterone develop primary resistance to this drug and nearly all patients experience disease progression. Here we describe a phase 1b study that will evaluate the combination of bavdegalutamide with abiraterone at the initiation of progression on abiraterone (prostate-specific antigen [PSA] progression without radiographic progression) to test if the addition of bavdegalutamide will overcome resistance to abiraterone and re-establish the AR pathway blockade in patients with prostate cancer. Methods: Eligible patients are men ≥18 years of age with histologically, pathologically, or cytologically confirmed adenocarcinoma of the prostate and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients must be receiving ongoing treatment with stable doses of abiraterone and a concomitant corticosteroid for mCRPC or CSPC and have PSA progression ≥16 weeks after initiation of abiraterone, ≥2 rising PSA values measured ≥1 week apart, and no radiographic evidence of disease progression while receiving abiraterone. Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone analogue or inhibitor or orchiectomy is required. Prior treatment with enzalutamide, apalutamide, darolutamide, or experimental AR-directed therapies is not permitted. Bavdegalutamide, abiraterone, and a corticosteroid will be administered daily in 28-day cycles. Primary objectives are to evaluate the safety and tolerability of bavdegalutamide plus abiraterone and determine the recommended phase 2 dose and schedule of this combination (based on the incidence of first-cycle dose-limiting toxicities and the frequency and severity of adverse events and laboratory abnormalities). Clinical trial information: NCT05177042.
SCOUT-1: Prospective non-interventional study in patients with BRCA/HRD-tested ovarian cancer (OC) eligible for first-line (1L) platinum-based chemotherapy (NOGGO ov54).
Authors: Wimberger Pauline , Pietzner Klaus , Braicu Ioana , Glowik Regina , Rose Matthias , Sehouli Jalid 
Published: June 2022

TPS5608 Background: Two third of patients with OC, have an advanced stage at initial diagnosis accompanied with poor prognosis. Results from landmark trials of maintenance therapy (MTX) with poly ADP ribose polymerase inhibitors (PARPi), especially in tumors associated with homologous recombination deficiency (HRD), like BRCA-mutated tumors, led to the strong recommendation on testing and treatment procedures in the clinical routine in patients newly diagnosed with advanced high-grade epithelial OC. The translation of these guidelines into clinical routine affects care management and therefore needs to be evaluated. This study aims to gain new insights into current real-world biomarker testing and 1L-treatment patterns together with clinical and patient-reported outcomes of patients with newly diagnosed advanced OC in Germany and to capture the influence of 1L treatment (with or without PARPi MTX) on medical routine and patient needs. Methods: SCOUT-1 is a national prospective, observational study (NCT04830709) to collect clinical real-world and patient-reported outcome (PRO) data in patients newly diagnosed with histologically confirmed advanced (FIGO stage III or IV) high-grade epithelial ovarian, fallopian-tube, or primary peritoneal cancer in Germany. Selection criteria include written informed consent, completed surgery (if applicable), eligible for platinum-based chemotherapy, BRCA1/2 mutation tested and willingness/ability to report PROs electronically. About 750 patients are planned to be included in up to 80 sites (hospitals or office-based). The primary objective is to determine the effectiveness of standard treatment sequences by estimating progression-free survival according to investigator’s assessment. Further focus is to describe biomarker-testing algorithm, patient selection and to assess patients’ QoL, symptoms, needs, as well as patients’ expectations. Importantly, SCOUT-1 will help to collect long-term data as patients will be followed for up to 7 years. First-subject-was included in the study in June 2021. Study completion date is planned in Q2 2032.
PERCEPTION: Phase II investigational study of pembrolizumab combination with chemotherapy in platinum-sensitive recurrent low-grade serous ovarian cancer— A NOGGO trial.
Authors: Grabowski Jacek P. , Pietzke Lea-Jean , Zocholl Dario , Harter Philipp , Heitz Florian , Chekerov Radoslav , Sehouli Jalid 
Published: June 2022

TPS5613 Background: Low-grade serous ovarian cancer (LGSOC) represents a minority within the group of invasive epithelial ovarian malignancies. Recent analyses showed a very limited responsiveness to chemotherapy in LGSOC. Since bevacizumab many years ago, none other agents have been approved in LGSOC. There is a high demand of new therapy combinations with modern substances to improve the response rate and prognosis in this group of patients. Immune check-point inhibitors provide a new possibility which showed to be effective in different malignant diseases as well as in selected ovarian cancer patients. In this study, the standard chemotherapy is going to be combined with pembrolizumab in recurrent LGSOC cases with therapy free interval (TFI) over 6 months after last platinum-based chemotherapy. To the authors knowledge no comparable studies have been performed or planned. If our trial should show pembrolizumab effectivity in LGSOC, it would be a signal and impulse for future clinical studies in this rare disease. Methods: PERCEPTION/NOGGO-ov44 (NCT04575961) clinical trial is a multi-center, single-arm phase 2 study to evaluate pembrolizumab therapy concomitant to platinum-based chemotherapy (carboplatin plus pegylated liposomal doxorubicin, carboplatin plus gemcitabine or carboplatin monotherapy) and as maintenance in recurrent low-grade serous ovarian cancer cases. LGSOC patients with progression or recurrence at least six months after most previous platinum-containing therapy and in good general performance (ECOG 0 or 1) are eligible to participate in this clinical trial. The primary objective is the 12 months progression free survival (PFS) rate. Secondary end-points include overall survival, response rate (RR), PFS and RR according to Ki67 expression levels, time to first subsequent therapy (TFST) and its response, safety and quality of life. The trial is planned according to Simon’s two-stage design with total sample size up to 33 patients. The null hypothesis is PFS-rate after 12 months of 20%. In the first phase 18 patients will be enrolled and if at least 5 patients show PFS after 12 months the study is going to be continued with an additional 15 patients. The trial is claimed successful, if at least 11 patients show PFS after 12 months. Assuming a true PFS-rate of 40%, this trial has 5% type I error rate and 80% power. Clinical trial information: NCT04575961.