bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II single-arm trial of niraparib in platinum-sensitive metastatic castration-resistant prostate cancer with DNA repair defects (PLATPARP).
Authors: Welch Erin Catherine , Torres Alexandra , Miller Joann , Louie Jennifer , Lee Daniel , Haas Naomi B. , Takvorian Samuel U , Maxwell Kara Noelle , Domchek Susan M. , Narayan Vivek 
Published: January 2024

TPS255 Background: The optimal use of PARP inhibitor (PARPi) therapy is evolving for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring germline and/or somatic homologous recombination repair gene mutations (HRRm). The sensitivity to platinum-based chemotherapy may predict improved clinical outcomes with PARPi. ‘Maintenance’ PARPi strategies are routinely used in patients with advanced ovarian and pancreatic malignancies with HRRm following an initial clinical response to platinum-based chemotherapy. Platinum-based chemotherapy is increasingly used in patients with mCRPC and HRRm as either a monotherapy or in combination with taxanes, but yields clinical responses of limited duration and is hindered by cumulative toxicities. We hypothesize that maintenance niraparib, a PARPi with demonstrated activity in mCRPC with HRRm, will prolong clinical responses to platinum-based chemotherapy with manageable toxicity in mCRPC patients harboring germline and/or somatic HRRm. Methods: We are conducting an open-label, single-arm, phase II study to evaluate the clinical benefit of maintenance niraparib in biomarker-defined, platinum-sensitive mCRPC patients. Eligible subjects harbor a pathogenic germline and/or somatic mutation in BRCA1/2, ATM, FANCA, CDK12, RAD51B, RAD54L, PALB2, CHEK2, HDAC2, or BRIP1 and have received at least 3 cycles (or minimum 9 weeks) of platinum-based chemotherapy for the treatment of mCRPC per investigator discretion. Following ≥4 weeks since completion of chemotherapy, subjects without evidence of clinical or radiographic disease progression receive investigational treatment with maintenance niraparib (200 mg daily). The primary objective is an improvement in 6 month PFS rate (PFS6) (H0: PFS6 rate 25%; H1: PFS6 rate 50%; power 0.77 with one-sided α = 0.05). Serial plasma samples are obtained for correlative analyses of markers of response and/or resistance to maintenance niraparib. Eleven of a planned total of 18 subjects have enrolled (N=4 germline BRCA2; N=1 germline BRCA1; N=3 somatic BRCA2; N=1 germline PALB2; N=1 germline ATM; N=1 germline CHEK2). This investigator-initiated study incorporates a novel, combined genetic and clinical patient-selection approach for PARPi therapy to optimize clinical outcomes. Clinical trial information: NCT04288687 .
Rezvilutamide in combination with androgen-deprivation therapy, with or without salvage radiotherapy, for patients experiencing biochemical recurrence following radical prostatectomy: A multi-center, open-label, two-cohort study.
Authors: Zhang Shun , Xu Linfeng , Qiu Xuefeng , Zhuang Junlong , Zou Qing , Wang Junqi , Guo Hongqian 
Published: January 2024

TPS355 Background: Rezvilutamide, a novel androgen-receptor inhibitor exhibiting minimal blood-brain barrier penetration, has demonstrated robust antitumor efficacy in metastatic castration-resistant prostate cancer and high-volume, metastatic, hormone-sensitive prostate cancer, which received approval from the Chinese National Medical Products Administration in 2022. The standard management for biochemical recurrence (BCR) post-prostatectomy typically involves androgen-deprivation therapy (ADT) alone or in combination with salvage radiotherapy (SRT). This study aims to evaluate the efficacy and safety of rezvilutamide plus ADT, with or without SRT for patients with BCR post-prostatectomy. Methods: In this multi-center, open-label, two-cohort study, patients with postoperative pathology-confirmed pN0 or pNx prostate adenocarcinoma who manifested BCR subsequent to radical prostatectomy (evidenced by two successive elevated serum prostate-specific antigen [PSA] measurements between 0.2-2 ng/ml, without identifiable local or metastatic recurrence on computed tomography and bone scans) would be enrolled. Cohort 1 participants will undergo 6 months of ADT, 6 cycles of rezvilutamide (240 mg/day, spanning 28 days per cycle), and SRT. Those in Cohort 2, either declining or ineligible for SRT, will receive 12 months of ADT combined with 12 cycles of rezvilutamide. The choice of ADT regimens rests with the investigators. The primary endpoints are the 2-year biochemical progression-free survival (bPFS) rate for Cohort 1 and the 3-year bPFS rate for Cohort 2. Secondary endpoints encompass bPFS, radiographic PFS, metastasis-free survival, and rates of undetectable PSA (with PSA levels < 0.1 ng/ml). Additionally, safety profiles, overall quality of life, testosterone recovery rates post-treatment initiation, and the time to testosterone recovery post-treatment discontinuation will be appraised. The study acquired ethical approval on November 24th, 2022, and subsequently commenced recruitment. As of now, 22 out of the planned 96 patients have been enrolled. Clinical trial information: NCT05753566 .
Strategic treatment pause of first-line immune checkpoint inhibitor + VEGFR-tyrosine kinase inhibitor in patients with good or intermediate risk metastatic renal cell carcinoma (mRCC) in response at 1 year of treatment (SPICI-GETUG R05): A non-inferiority randomized clinical trial.
Authors: Gross-Goupil Marine , Lefort Felix , Larroquette Mathieu , Asselineau Julien , Frison Eric , Albiges Laurence , Ravaud Alain 
Published: January 2024

TPS487 Background: Treatment of mRCC consists of combination of either Immune Checkpoint Inhibitor (ICI)-Tyrosine Kinase Inhibitor (TKI) for all IMDC prognosis group, or ICI-ICI for intermediate and unfavorable IMDC groups. Treatments are maintained until disease progression or toxicity for a total duration of 2 years for ICI, in routine. Acceptability and feasibility of treatment pause of the TKI, with no detrimental effect on efficacy were reported in the prospective STAR trial. The good-risk population is characterized by prolonged survival, close to that reported in the intermediate risk population group with a single adverse prognostic factor. Therefore, a pause of ICI-TKI could improve quality of life, safety, and total cost of care without detrimental impact on oncologic outcomes. Methods: This non-inferiority, randomized, open-label, multicenter, parallel-group trial (NCT05219318) aims to compare treatment pause versus treatment continuation in good or intermediate risk mRCC patients with only one prognostic factor and a confirmed objective response (complete or partial) at 12 months of treatment with ICI-TKI. 372 patients (186 in France) will be recruited in tertiary hospitals and randomized in a 1:1 ratio with stratification by center, prognostic group (good/intermediate) and response (complete/partial). The primary objective is to test the non-inferiority of treatment pause versus continuation, with the estimation of the difference in 12-month progression rate after randomization, and its one-sided 97.5% confidence interval. The non-inferiority margin is set at 15%. An interim safety data monitoring at 6 months after randomization of the first third of participants (i.e. 60 per arm) will check progression rate after treatment pause. A formal interim futility analysis will be performed when 50% of the study sample reaches the primary outcome time point, using a Bayesian predictive power stopping rule and a futility threshold set at 20%. Secondary objectives are overall safety and tolerability, health-related quality of life, anxiety and depression, quality-adjusted survival, 2-year overall and progression-free survival. Others objectives include progression patterns (site, known lesions, or/and new lesions), subsequent treatment (type, efficacy), in the experimental arm. In France, healthcare resource utilization and costs at 12 months will be compared. The first participant was randomized in January 2023. 27 centers in France were selected and are gradually/progressively opening. The opening of European centers is being planned. Health Ministry and National Cancer Institute Funds. Clinical trial information: NCT05219318 .
The role of cytoreductive nephrectomy in metastatic renal cell carcinoma in immune-oncology era (SEVURO-CN): A study protocol for a multi-center, prospective, randomized trial.
Authors: Park Jee Soo , Kim Jongchan , Jeon Jinhyung , Lee Jongsoo , Jang Won Sik , Lee Seung Hwan , Han Woong Kyu , Choi Young Deuk , Koo Kyo Chul , Cho Kang Su , Chung Byung Ha , Ham Won Sik 
Published: January 2024

TPS490 Background: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear in the immuno-oncology (IO) era. The results of two randomized trials, CARMENA and SURTIME, questioned the role and timing of CN. However, despite the latest advances in the systemic treatment of mRCC, previous trials have only used targeted therapy, and no studies have fully investigated the role of CN in immune checkpoint inhibitor (CPI) settings, and there is an urgent need for future studies to better define the role and timing of CN. Methods: This study is an open-label, multi-center, parallel, prospective, randomized, interventional clinical study to evaluate the efficacy of CN in combination with CPIs in mRCC patients with International mRCC Database Consortium (IMDC) intermediate- and poor-risk. Synchronous mRCC patients with ≤3 IMDC risk features will be randomly allocated to three groups (1, upfront CN; 2, deferred CN; and 3, systemic therapy (ST) only). For ST, the nivolumab plus ipilimumab combination regimen, one of the standard regimens for intermediate- and poor-risk mRCC, is chosen. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, objective response rate, number of participants with treatment-related adverse events, and number of participants with surgical morbidity. We will analyze the genetic mutation profiles of the tumor tissue, circulating tumor DNA, urine tumor DNA, and tumor-infiltrating lymphocytes. The gut and urine microbial communities will be analyzed. The study will begin in 2023 and will enroll 40 patients. Clinical trial information: NCT05753839 .
Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587).
Authors: Serzan Michael Thomas , Jegede Opeyemi , Bilen Mehmet Asim , Braun David A. , Einstein David Johnson , Haas Naomi B. , Hammers Hans J. , King Jennifer , Runcie Karie , Sosman Jeffrey A. , Sternberg Cora N. , Yang Yuanquan (Aaron) , Choueiri Toni K. , Signoretti Sabina , Atkins Michael B. 
Published: January 2024

TPS492 Background: First-line treatment for patients with metastatic clear cell renal cell carcinoma (mccRCC) often includes an anti-PD1 inhibitor in combination with either an anti-CTLA inhibitor (IO/IO) or a VEGF receptor tyrosine kinase inhibitor (TKI) (IO/TKI). Although some patients treated with nivolumab/ipilimumab (Nivo/Ipi) (IO/IO) experience durable responses leading to treatment free intervals, over two-thirds experience disease progression. Resistance to Nivo (anti-PD1) monotherapy has been associated with increased presence of a subpopulation of Tregs in the tumor microenvironment. Botensilimab (Bot) is an IO agent that leverages novel FcyR-associated mechanisms of action to enhance T cell priming, deplete intratumoral Tregs and enhance myeloid activation. Combination botensilimab/balstilimab (Bot/Bal) (anti-CTLA/anti-PD1) has shown impressive anti-tumor activity in diseases where Nivo/Ipi has shown little to no efficacy. Methods: ARCITECT is a phase II, multicenter study evaluating the efficacy and safety of Bot/Bal relative to Nivo/Ipi. Patients with mccRCC ( favorable, intermediate, or poor risk), no prior systemic therapy (including adjuvant or neoadjuvant), and at least one measurable lesion as defined by RECIST 1.1 are eligible for enrollment. 120 patients will be randomized in a 2:1 fashion to Arm A (Bot/Bal induction followed by Bal maintenance) or Arm B (Nivo/Ipi induction followed by Nivo maintenance) each for a maximum of 2 years. Stratification factors include IMDC risk groups and sarcomatoid histology. The primary endpoint is overall response rate (ORR) per RECIST 1.1. We hypothesize that Bot/Bal will lead to a superior ORR (55%) relative to Nivo/Ipi (40%). This trial has > 90% power to detect the alternative hypothesis while maintaining a one-sided significance level of not more than 0.10 using the exact binomial. The study will be monitored for early stopping in favor of the null hypothesis based on a Simon’s two stage design. In the first stage, 69 patients will be enrolled (Arm A:46 and Arm B:23). If at the end of the first stage, Arm A has either at least 18/42 (42.8%) of eligible patients responding or an ORR at least numerically equivalent to that for eligible patients in Arm B, then the trial will progress to the second stage. The primary endpoint will be met if there are 38/80 responders (ORR > 47.5%) in Arm A. Key secondary endpoints include landmark progression-free survival, treatment-free survival and rates of immune-related adverse events. Correlative studies will explore immune and molecular predictors of response and resistance to IO/IO in tumor and blood. Clinical trial information: NCT05928806 .
MAIN-CAV: Phase III randomized trial of maintenance cabozantinib (CABO) and avelumab (Av) vs Av after first-line platinum-based chemotherapy in patients (pts) with metastatic urothelial cancer (mUC; Alliance A032001).
Authors: Gupta Shilpa , Ballman Karla V. , Apolo Andrea B. , Sridhar Srikala S. , Chen Ronald C. , Wen Yujia , Yen Aihua Edward , Grivas Petros , Tan Alan , Baghaie Shiva , Galsky Matt D. , Morris Michael J. , Rosenberg Jonathan E. 
Published: January 2024

TPS714 Background: 1st-line induction platinum-based chemotherapy followed by switch maintenance Av is the current preferred standard of care in patients (pts) with aUC who do not progress after platinum-based chemotherapy. There is an significant need to further improve outcomes by combining Av with an effective, non-cross resistant therapy with non-overlapping toxicity. CABO is an oral inhibitor of MET, VEGFR and TAM family receptors involved in tumor growth, angiogenesis and immune cell regulation and has shown efficacy in UC in combination with PD-1/PD-1L1 inhibitor. We hypothesized that CABO-Av combination would improve survival vs Av alone and have an acceptable safety profile as switch maintenance therapy in mUC. Methods: MAIN-CAV is a phase III randomized, multicenter, international trial for pts with locally advanced/metastatic UC (including cN3M0 only)) who do not progress after 4-6 cycles of any platinum-based chemotherapy (gem-cis, gem-carbo, MVAC or ddMVAC). 654 adults are randomized 1:1 within 3-10 weeks (wk) after last dose of chemotherapy to receive Av 800 mg IV every 2 wk or Av and CABO 40 mg daily for up to 2 yrs. Key eligibility criteria include ECOG PS 0-1, no prior use of anti-PD(L)1, no CNS metastases, no major surgery within 4 wks, no uncontrolled hypertension or cardiovascular disorders. Pts are stratified based on 1) best response to 1L chemotherapy: complete vs partial response vs stable disease and 2) presence vs absence of visceral metastases. The primary endpoint is overall survival (OS) with assumptions of 1-sided alpha 0.025, power 80%, median OS 21 months (mo) with Av and hazard ratio 0.75, thus hypothesizing median OS 28 mo on CABO-Av. Key secondary endpoints include progression-free survival, safety, tolerability, and efficacy of CABO-Av vs Av alone based on RECIST 1.1 and iRECIST criteria (and PD-L1 status).Quality of life (QOL) are assessed using EQ-5D-5L, PROMIS-Fatigue 4a, EORTC QLQ-C30, EORTC QLQ-BLM30 between pts on CABO-Av vs Av alone. Biomarkers of response and resistance to Av will be assessed using baseline archival tissues, baseline and serial blood, ctDNA, stool and urine. Imaging studies will test the correlation of established and new radiomic signatures with survival, adverse events and QOL and incorporate both radiologic and biologic features to assess their potential association with outcomes. This trial would be the first to systematically address whether adding the multitargeted TKI, CABO, to Av improves survival vs Av alone as 1L maintenance therapy. https://acknowledgments.alliancefound.org . Support: U10CA180821, U10CA180882; U24CA196171, U10CA180863 (CCTG); Clinical trial information: NCT05092958 .
A phase 1 study of IO102-IO103 vaccine plus pembrolizumab in patients with BCG-intolerant or unresponsive non-muscle invasive bladder cancer (NMIBC).
Authors: Veeravelli Sumana , Dall'era Marc , Gulati Shuchi , Mitsiades Nicholas , Verma Rashmi , Evans Christopher P. , Chandrasekar Thenappan , Monjazeb Arta Monir , Lara Primo N , Parikh Mamta 
Published: January 2024

TPS716 Background: Pembrolizumab, an anti-PD1 antibody, is a treatment option for high-risk BCG-unresponsive NMIBC, but has a modest complete response (CR) rate of 41% at 3 months, and a median duration of CR of 16.2 months. IO102-IO103 is a novel immune-modulating cancer vaccine that stimulates activation of T cells targeting indoleamine-2,3-dioxygenase 1 (IDO1) and PDL1-positive cells, resulting in potentially increased susceptibility to anti-PD-1 blockade. Combination IO102-IO103 with nivolumab showed encouraging clinical activity and tolerability in previously anti-PD-1 naïve metastatic melanoma patients (NCT03047928). The existing data for synergistic effects of IO102-IO103 in combination with anti-PD1 therapy and the known expression of IDO in urothelial carcinoma lend rationale to this phase I trial designed to assess the feasibility, safety, and toxicity of IO102-IO103 plus pembrolizumab in patients with BCG-intolerant or unresponsive NMIBC. Methods: This open-label, single arm, phase 1 study enrolls patients with BCG-unresponsive or intolerant high-risk NMIBC who are ineligible for or have declined cystectomy and have adequate ECOG performance status (0-2), hematologic function, and end organ function. High-risk NMIBC is defined as T1, high-grade Ta, or CIS/Tis, with predominantly urothelial cell histology. Exclusion criteria include known active autoimmune disorders requiring immunosuppressive therapy or prior checkpoint inhibitor therapy. Eligible patients will be treated with pembrolizumab 200 mg IV on Day (D) 1, and IO102-IO103 85 mcg SQ on D1 and 8 of a 21-day cycle for the first two cycles, after which IO102-IO103 dosing will be D1 only, with treatment for up to 2 years. The primary endpoints of feasibility, safety, and toxicity will be evaluated by CTCAE v5.0 criteria and will be met if ≥10 patients out of 12 are able to complete the first cycle without experiencing pre-specified treatment-limiting toxicities. Key secondary endpoints include CR rate at 3 months, median duration of response, and cystectomy-free survival at 18 months. Biopsy specimens and serial urine and blood samples will be collected to evaluate potential biomarkers of response. Clinical trial information: NCT05843448 .
WUTSUP-02-II-Neo-Dis-Tis: Investigating the efficacy and safety of neoadjuvant tislelizumab plus disitamab vedotin with adjuvant tislelizumab in upper urinary tract carcinoma—A phase II multi-center study.
Authors: Bao Yige , Liao Xinyang , Zhang Peng , Zeng Hao , Liu Jiyan , Wei Qiang 
Published: January 2024

TPS718 Background: Upper tract urothelial carcinoma (UTUC) and urothelial bladder cancer (UBC) are frequently referred to as “disparate twins” despite their common tissue origin. They exhibit varying biological behaviors, prognostic outcomes, and responses to treatment. It is crucial to conduct dedicated clinical trials for UTUC as a separate entity rather than relying solely on UBC study results, giving that UTUC lags in evidence quantity and quality compared to UBC. Despite the superior outcomes of neoadjuvant treatment over adjuvant treatment in UBC trials, the currently available evidence for neoadjuvant therapy of UTUC remains limited in quantity and diversity, as the largest trial, POUT, is focused on adjuvant therapy. Additionally, the limited number of neoadjuvant trials for UTUC primarily utilize chemotherapy-based regimens, with little investigation into combination therapies. Of note, UTUC patients frequently have impaired renal functions, making a chemotherapy-independent approach a desirable alternative. On the other hand, given the short duration of neoadjuvant therapy, a combination therapy strategy appears to be necessary, especially with the increasing interest in immune therapy maintenance after surgery. Tislelizumab has demonstrated efficacy in patients with advanced or metastatic urothelial carcinoma. Disitamab Vedotin, a HER2-targeting antibody-drug conjugate (ADC), has demonstrated robust clinical efficacy in metastatic urothelial carcinoma patients with HER2 2+ or 3+ expression. Disitamab Vedotin in combination with PD-1 immunotherapy has shown remarkable results in locally advanced or metastatic urothelial carcinoma, regardless of HER2 expression, indicative of a synergistic effect between ADC and PD-1 immunotherapy. In this study, we aim to conduct a prospective phase II trial to investigate the efficacy and safety of neoadjuvant tislelizumab plus Disitamab Vedotin followed by adjuvant tislelizumab in patients with high-risk UTUC. Methods: This multi-center phase II trial aims to enroll 45 patients with histologically confirmed UTUC at clinical stage cT2-4N0M0 or cT1-4N1-2M0. Neoadjuvant therapy includes 4 cycles of Tislelizumab (200mg for each 3-week cycle) in combination with Disitamab Vedotin (2.0mg/kg for each 3-week cycle). Radical nephroureterectomy (including bladder cuff resection and regional lymph node dissection if indicated) will be performed if there is no obvious contraindication within 3-6 weeks after the final neoadjuvant therapy administration. Postoperative adjuvant treatment with 8 cycles of tislelizumab will be provided. The primary endpoint is pathological complete response rate. Secondary endpoints include overall survival, local recurrence free survival, distant metastasis free survival, FACT–G. Clinical trial information: ChiCTR2300067836 .