bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase III, randomized, open label, multicenter, global study of efficacy and safety of durvalumab in combination with gemcitabine+cisplatin (G+C) for neoadjuvant treatment followed by durvalumab alone for adjuvant treatment in muscle-invasive bladder cancer (MIBC) (NIAGARA).
Authors: Powles Thomas , Meeks Joshua J , Galsky Matt D. , Van Der Heijden Michiel Simon , Nishiyama Hiroyuki , Al-Ahmadie Hikmat , Gupta Ashok Kumar , Ye Jiabu , Donegan Sarah E. , Ghiorghiu Dana C. , Ferro Salvatore , Catto James WF 
Published: May 2019

TPS4592 Background: Management of MIBC includes both surgery and systemic therapy. Neoadjuvant, cisplatin-based combination chemotherapy has demonstrated improved pathologic complete response (pCR), event-free survival (EFS), and OS compared with radical cystectomy alone. Many patients still develop recurrence, including progression to metastasis. Novel strategies such as combining chemotherapy and immunotherapy in a neoadjuvant setting and consolidating response post cystectomy in the adjuvant setting may improve clinical outcomes. Durvalumab is a selective, high affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80. PD-L1 inhibition with durvalumab, in combination with a standard neoadjuvant regimen (G+C), may improve immune-mediated antitumor response and increase the rates of pathologic responses and long-term survival. Methods: NIAGARA (NCT03732677) is a Phase 3, randomized, open-label, multicenter, global study that will enroll ~1050 patients randomized (1:1) to durvalumab and G+C combination (Arm 1) or G+C (Arm 2) as neoadjuvant chemotherapy prior to radical cystectomy. Following radical cystectomy and during adjuvant therapy, patients in Arm 1 will receive durvalumab monotherapy for 8 cycles (8 months); patients in Arm 2 will receive no adjuvant treatment. Patients with resectable MIBC (clinical stage T2N0M0-T4aN0M0) with transitional cell histology planning to undergo a radical cystectomy will be included. Primary endpoints are pCR rates at time of cystectomy following neoadjuvant treatment and EFS. Secondary and exploratory endpoints include proportion of patients who achieve pathologic response <P2 (stages Pa, P1, and carcinoma in situ) at time of cystectomy following neoadjuvant treatment, EFS at 24 months, metastasis-free survival, proportion of patients who undergo cystectomy, and OS at 5 years. Safety, patient-reported outcomes, pharmacokinetics, immunogenicity, and biomarkers will also be assessed. Enrollment opened in Dec 2018. Clinical trial information: NCT03732677.
EV-103: Enfortumab vedotin plus pembrolizumab and/or chemotherapy for locally advanced or metastatic urothelial cancer.
Authors: Hoimes Christopher J. , Rosenberg Jonathan E. , Petrylak Daniel Peter , Carret Anne-Sophie , Melhem-Bertrandt Amal , Flaig Thomas W. 
Published: May 2019

TPS4593 Background: PD-(L)1-targeted immune checkpoint inhibitors (CPIs), such as pembrolizumab (P), are approved for patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) who progress after platinum, are ineligible for first-line (1L) cisplatin (PD-L1 positive), or are ineligible for 1L platinum. The ORR for CPI in all treated pts is ~25%, and a combination approach may provide additional benefit. Enfortumab vedotin (EV), an investigational antibody-drug conjugate, delivers the microtubule-disrupting agent monomethyl auristatin E to cells expressing Nectin-4, found in 97% of mUC pt samples (Petrylak ASCO 2017). In a phase 1 study (NCT02091999), EV (1.25 mg/kg) was generally well tolerated with a confirmed ORR of 43% in 112 mUC pts (Rosenberg ASCO-GU 2019). These encouraging results, with the potential for an enhanced immune response, suggest that EV+P may improve response rates and extend response durability. Methods: EV-103, a phase 1b trial for non–resectable la/mUC pts with no prior CPI, added an additional 4 cohorts (Parts 2 and 3) in an Oct 2018 amendment. It is now expected to enroll ~159 pts. Dose escalation pts (EV+P, 1L or 2L) must be ineligible for 1L cisplatin-based chemotherapy or have disease progression during/following treatment with ≥1 platinum-containing regimen. Dose expansion (Part 1) will evaluate EV+P in 1L (Cohort A) and 2L settings (Optional Cohort B). Part 2 will evaluate 1L EV+cisplatin (Cohort D), 1L EV+carboplatin (Cohort E), and 1L or 2L EV+gemcitabine (Optional Cohort F). Part 3 (Cohort G) will evaluate 1L EV+P+cisplatin or carboplatin, depending on pts cisplatin-eligibility. In all cohorts, pts receive EV on Days 1 and 8 of each 3-week cycle. In combination therapies, pts receive P, cisplatin, and carboplatin on Day 1 or gemcitabine on Days 1 and 8 of each cycle. The primary objective is to assess the safety/tolerability of EV+P and/or chemotherapy. Secondary objectives are establishing EV recommended dose for combination therapies, assessing ORR per RECIST for all cohorts and per iRECIST for therapies with pembrolizumab, as well as assessing disease control rate, duration of response, PFS, OS, PK, and biomarkers. The study opened Oct 2017. Clinical trial information: NCT03288545.
PDIGREE: An adaptive phase 3 trial of PD-inhibitor nivolumab and ipilimumab (IPI-NIVO) with VEGF TKI cabozantinib (CABO) in metastatic untreated renal cell cancer (Alliance A031704).
Authors: Zhang Tian , Ballman Karla V. , Choudhury Atish Dipankar , Chen Ronald C. , Watt Colleen , Wen Yujia , Zemla Tyler , Emamekhoo Hamid , Gupta Shilpa , Morris Michael J. , George Daniel J. , Choueiri Toni K. 
Published: May 2019

TPS4596 Background: First-line treatment of mRCC has rapidly changed to include IPI-NIVO or CABO, with clinical benefit of each based on the Checkmate 214 and CABOSUN trials. Combination immunotherapy with VEGF therapies have shown benefit in the JAVELIN 101 and KEYNOTE 426 trials over sunitinib. It is yet unclear which patients (pts) benefit most from combination immunotherapy-VEGF inhibitors, and the optimal sequence of drugs. Methods: In an adaptive, randomized, multicenter, phase 3 trial (Alliance A031704, PDIGREE), pts will start treatment with induction IPI 1mg/kg and NIVO 3mg/kg intravenously (IV) once every 3 weeks. Key inclusion criteria include clear cell mRCC, IMDC intermediate or poor risk, Karnofsky performance status >70, and no prior treatments for mRCC. Based on 3-month radiographic assessment (after completing IPI-NIVO combination), pts with complete responses (CR) will undergo maintenance NIVO 480mg IV every 4 weeks, pts with progression of disease (PD) will switch to CABO 60mg oral daily, and pts with non-CR/non-PD will be randomized to NIVO 480mg IV every 4 weeks versus NIVO 480mg IV every 4 weeks with CABO 40mg oral daily. Randomization will be stratified by IMDC risk criteria and presence of bone metastases. The primary endpoint of the study is overall survival (OS). We hypothesize that 3-year OS rate will improve to 70% for NIVO-CABO compared to 60% for NIVO alone; to achieve 85% power with a two-sided alpha of 0.05 and exponential distribution, 696 patients will be randomized. Accounting for 30% patients with either CR or PD, and 5% dropout from toxicity, up to 1046 pts will be enrolled. Key secondary endpoints include PFS, 12-month CR rate, ORR based on RECIST 1.1 and irRECIST criteria, and toxicity profiles. Quality of life will be assessed based on the FKSI-19, PROMIS-fatigue, and EQ5D-5L questionnaires. Biomarkers associated with CR and association of IL-6 with treatment benefit will be assessed. Other tissue-based and plasma-based biomarkers are planned. Enrollment will begin this year. Support from UG1CA189823, U24CA196171; https://acknowledgments.alliancefound.org . Clinical trial information: NCT03793166.
TALAPRO-2: Part 2 (P2) of the placebo-controlled phase 3 study of talazoparib (TALA) with enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Agarwal Neeraj , Shore Neal D. , Dunshee Curtis , Karsh Lawrence Ivan , Sullivan Beth , Di Santo Nicola , Elmeliegy Mohamed , Lin Xun , Quek Ruben G.W. , Czibere Akos Gabor , Fizazi Karim 
Published: May 2019

TPS5092 Background: ENZA is approved to treat men with CRPC. TALA is a poly(ADP-ribose) polymerase (PARP) inhibitor that inhibits PARP1/PARP2 and traps PARP on DNA, preventing DNA damage repair (DDR), and causing cell death in BRCA1/2-mutated cells. TALA is approved in the US to treat germline BRCA1/2-mutated HER2- locally advanced/metastatic breast cancer. A combination of TALA with ENZA in mCRPC may improve clinical outcomes. TALAPRO-2 (NCT03395197) is a 2-part study to evaluate the efficacy, safety, pharmacokinetics and (patient) pt-reported outcomes of the combination treatment. The focus here is on P2 of TALAPRO-2. Methods: Approximately 860 pts are planned to be enrolled in P2 from multinational sites. Pts are aged ≥18 years, have asymptomatic/mildly symptomatic mCRPC, Eastern Cooperative Oncology Group performance status ≤1, no brain metastases, and have not received taxanes/novel hormonal therapy (NHT). P2 is a randomized double-blind study that will evaluate safety, efficacy, and pt-reported outcomes of TALA (0.5 mg QD) + ENZA (160 mg QD) vs placebo + ENZA (160 mg QD). Pts will be randomized to 1 of 2 treatment groups: TALA + ENZA, or matching placebo + ENZA. Randomization will be stratified by prior treatment with NHT for castration-sensitive prostate cancer (CSPC) or prior treatment with taxane-based chemotherapy for CSPC (yes/no) and DDR mutation status (deficient vs. nondeficient/unknown). The primary endpoint is radiographic progression-free survival (rPFS), defined as time to progression in soft tissue per RECIST v1.1 or in bone per PCWG3 criteria or death. The key secondary endpoint is overall survival (OS). Efficacy will be assessed by radiography every 8 weeks up to week 25 and every 8-12 weeks thereafter. The analyses of rPFS will be compared between TALA in combination with ENZA and placebo in combination with ENZA by using a 1-sided stratified log-rank test. OS will be evaluated separately in the all comers and the DDR-deficient populations. Pt recruitment is ongoing. Results: n/a. Conclusions: n/a. Clinical trial information: NCT03395197.
PROTEUS: A randomized, double-blind, placebo (PBO)-controlled, phase 3 trial of apalutamide (APA) plus androgen deprivation therapy (ADT) versus PBO plus ADT prior to radical prostatectomy (RP) in patients with localized high-risk or locally advanced prostate cancer (PC).
Authors: Taplin Mary-Ellen , Gleave Martin , Evans Christopher P. , Efstathiou Eleni , Kantoff Philip W. , Ross Ashley , Shore Neal D. , Briganti Alberto , Hadaschik Boris A. , Heidenreich Axel , Rooney Oliver Brendan , Tian Shaozhou Ken , Wetherhold Lisa , Xu Weichun , Cheng Shinta , Kibel Adam S. 
Published: May 2019

TPS5100 Background: Patients (pts) with localized high-risk PC experience disease progression rates of approximately 50% after RP (Kane et al. J Urol. 2007). With the approval of next-generation androgen receptor inhibitors, neoadjuvant studies have shown that 6 months of androgen blockade may improve local disease control at the time of RP (McKay et al. Prostate Cancer Prostatic Dis. 2017; Taplin et al. JCO. 2014). The purpose of this study is to determine if treatment with APA plus ADT before and after RP in pts with localized high-risk or locally advanced PC results in an improvement in pathologic complete response (pCR) rate and metastasis-free survival (MFS) compared with PBO plus ADT. Methods: This international multicenter trial is enrolling pts with localized high-risk or locally advanced PC who are candidates for RP. Eligibility criteria: Any Gleason score (GS) ≥ 4 + 3 with ≥ 6 positive systematic biopsies (SB); any GS ≥ 4 + 3 with ≥ 3 SB and prostate-specific antigen (PSA) ≥ 20 ng/mL; GS ≥ 9 in ≥ 1 SB or targeted biopsies (TB); or ≥ 2 SB or TB with continuous GS ≥ 8, each with ≥ 80% involvement. Stratification: GS (7 or ≥ 8), cN0 or N1, and region (North America, Europe, or rest of world). Randomization: 1:1 to APA (240 mg) plus ADT (LHRHa) or PBO plus ADT. Pts will receive 6 treatment cycles, followed by RP, followed by an additional 6 cycles. Dual primary end points: pCR rate (to be assessed by blinded independent central pathology review) and MFS (to be assessed by blinded independent central radiology review [BICR]). Secondary end points: PSA-free survival and progression-free survival. Imaging with CT or MRI and bone scan will be conducted at baseline and then every 6 months following biochemical failure until documented distant metastasis by BICR, or death. Approximately 1500 pts will be enrolled globally over 3.0 years in 240 sites in 19 countries. An independent data monitoring committee is commissioned to review trial data. Clinical trial information: NCT03767244.
Randomized prospective phase 3 trial of 68Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT].
Authors: Calais Jeremie , Czernin Johannes , Fendler Wolfgang P , Elashoff David , Nickols Nicholas George 
Published: May 2019

TPS5101 Background: Salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence after prostatectomy offers long-term biochemical control in about 50–60% of patients. SRT is commonly initiated in patients with serum PSA levels < 1 ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. As such, SRT target volumes are usually drawn in the absence of radiographically visible disease. 68Ga-PSMA-11 (PSMA) PET/CT molecular imaging is highly sensitive and may offer anatomic localization of PCa biochemical recurrence. However, it is unclear if incorporation of PSMA PET/CT imaging into the planning of SRT could improve its likelihood of success. The purpose of this trial is to evaluate the success rate of SRT for recurrence of PCa after prostatectomy with and without planning based on PSMA PET/CT. Methods: We will randomize 193 patients to proceed with standard SRT (control arm 1, n = 90) or undergo a PSMA PET/CT scan (free of charge for patients) prior to SRT planning (investigational arm 2, n = 103). The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (BPFS) after initiation of SRT. Biochemical progression is defined by PSA ≥ 0.2 ng/mL and rising. The randomization ratio of 1:1.13 is based on the assumption that approximately 13% of subjects randomized to Arm 2 will not be treated with SRT because of PSMA-positive extra-pelvic metastases. These patients will not be included in the primary endpoint analysis but will still be followed. The choice of treating the prostate bed alone vs prostate bed and pelvic lymph nodes, with or without androgen deprivation therapy (ADT), is selected by the treating radiation oncologist. The radiation oncologist may change the radiation plan depending on the findings of the PSMA PET/CT scan. Any other imaging is allowed for SRT planning in both arms if done per routine care. Patients will be followed until either one of the following conditions occur: 5 years after the date of initiation of randomization, biochemical progression, diagnosis of metastatic disease, initiation of any additional salvage therapy, death. Discussion: This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa early BCR following radical prostatectomy. Clinical trial information: NCT03582774.
KEYNOTE-826: A phase 3, randomized, double-blind, placebo-controlled study of pembrolizumab plus chemotherapy for first-line treatment of persistent, recurrent, or metastatic cervical cancer.
Authors: Shapira-Frommer Ronnie , Alexandre Jerome , Monk Bradley , Fehm Tanja N. , Colombo Nicoletta , Caceres Maria V. , Hasegawa Kosei , Dubot Coraline , Li Jerry Jing , Stein Karen , Keefe Stephen Michael , Tewari Krishnansu Sujata 
Published: May 2019

TPS5595 Background: Cervical cancer arises in the setting of persistent infection with high-risk human papillomavirus subtypes. Many patients with early-stage and locally advanced carcinoma can be salvaged with radical surgery and chemoradiation, respectively. However, women with recurrent/metastatic disease represent a poor prognostic group with high unmet clinical needs. Incorporation of anti-angiogenesis therapy has emerged as a therapeutic option, but the survival benefit of 3.7 months over chemotherapy (CT) alone is modest (Tewari et al. NEJM 2014). Because viral tumor antigen-specific T cells reside predominantly in programmed cell death 1–expressing T-cell compartments, checkpoint inhibition may unleash a diverse antitumor T-cell response. Based on the 14.3% objective response in KEYNOTE-158, the US FDA granted accelerated approval to pembrolizumab (pembro) in June 2018 for second-line therapy and beyond. Methods: KEYNOTE-826 is a phase 3, randomized, double-blind, placebo-controlled, multinational trial of CT with pembro or with placebo for first-line treatment of recurrent, persistent, or metastatic cervical cancer. Patients not previously treated with CT for recurrence who are not amenable to curative treatment will be randomized 1:1 to CT + pembro 200 mg or placebo every 3 weeks. The CT regimen (paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5, with or without bevacizumab 15 mg/kg) will be selected by the investigator before randomization. Stratification factors include metastasis status at diagnosis, bevacizumab use (yes/no), and tumor PD-L1 status (combined positive score <1, 1 to <10, or ≥10). Treatment will continue until disease progression, unacceptable toxicity, or voluntary patient withdrawal for up to 35 cycles (~2 years). Primary endpoints are progression-free survival (PFS) per RECIST v1.1 assessed by blinded independent central review and overall survival. Secondary endpoints are objective response, duration of response, 12-month PFS, patient-reported quality of life, and safety. Enrollment is ongoing. Clinical trial information: NCT03635567.
ENGOT-Ov41/GEICO-69-O/ANITA trial: A phase III randomized, double-blinded trial of platinum-based chemotherapy (CT) with or without atezolizumab (ATZ) followed by niraparib maintenance with or without ATZ in patients with recurrent ovarian, tubal or peritoneal cancer (OC) and platinum treatment-free interval (TFIp) >6 months.
Authors: González-Martín Antonio , Colombo Nicoletta , Heitz Florian , Christensen Rene dePont , Selle Frédéric , Vergote Ignace , Oaknin Ana 
Published: May 2019

TPS5599 Background: Platinum-based CT is the treatment of choice for OC patients (pts) with TFIp > 6 months suitable for platinum. Niraparib is an oral PARP inhibitor that significantly prolongs the progression-free survival (PFS) of OC pts when given as maintenance therapy after a response to platinum-rechallenge (both in gBRCA and non-gBRCA mutated pts). Atz is a humanized monoclonal antibody targeting PD-L1 that showed activity in heavily pretreated OC pts. Combination of anti-PD-L1 and CT may improve the activity of the anti-PD-L1 antibody by increasing the amount of antigens released after immunogenic cell death induced by CT. Combination of PARPi and anti-PD-L1/PD-1 has shown synergy in preclinical models and promising clinical activity in certain indications. Methods: ANITA (NCT03598270) is a phase III, randomized (1:1), double-blinded, multi-center study to assess the efficacy of the addition of Atz to platinum-based doublet CT followed by maintenance niraparib in patients with recurrent high grade serous or endometrioid OC with a TFIp > 6 months. Approximately 414 patients with ECOG 0-1, known BRCA status, at least one measurable lesion and ≤ 2 prior lines will be randomized to placebo of Atz (Arm A) or Atz (Arm B) in combination with one of three possible standard platinum-based CT regimens (investigator’s choice) followed by maintenance niraparib in combination with placebo or Atz, according to randomization, if experiencing response or stable disease by RECIST after CT. Stratification factors: 1) Platinum-based regimen (paclitaxel-carboplatin vs gemcitabine-carboplatin vs PLD-carboplatin); 2) Platinum-free interval (6-12 vs > 12 months); and 3) BRCA status (mutated vs non-mutated). Dose of Atz is 1200 mg q3 weeks or 840 mg q2 weeks depending on the platinum-based regimen selected. Niraparib initial dose (300 vs 200 mg) is decided based on body weight and platelet counts after CT according to RADAR analysis. Primary endpoint is PFS based on investigator assessment by RECIST v1.1. Clinical trial information: NCT03598270.
ENGOT-OV43/KEYLYNK-001: A phase III, randomized, double-blind, active- and placebo-controlled study of pembrolizumab plus chemotherapy with olaparib maintenance for first-line treatment of BRCA-nonmutated advanced epithelial ovarian cancer.
Authors: Vergote Ignace , Sehouli Jalid , Salutari Vanda , Zola Paolo , Madry Radoslaw , Wenham Robert Michael , Korach Jacob , Pautier Patricia , Cibula David , Lheureux Stephanie , Hasegawa Kosei , Kim Byoung-Gie , Lai Chyong-Huey , González-Martín Antonio , Liu Qi , Keefe Stephen Michael , Puglisi Martina , Topuz Samet 
Published: May 2019

TPS5603 Background: There is a significant unmet need to develop new regimens for BRCA1/2-nonmutated advanced ovarian cancer (OC). The PARP inhibitor olaparib is approved for women with platinum-sensitive, recurrent OC regardless of BRCA1/2 status and, more recently, for newly diagnosed women with BRCA-mutated OC. In the TOPACIO/KEYNOTE-162 study, the combination of the PD-1–blocking antibody pembrolizumab (pembro) and niraparib demonstrated efficacy in platinum-resistant relapsed OCirrespective of BRCA1/2 status. ENGOT-OV43/KEYLYNK-001 (ClinicalTrials.gov, NCT03740165) is a phase 3, randomized, double-blind, active- and placebo-controlled study of pembro plus paclitaxel-carboplatin chemotherapy (CT) followed by olaparib maintenance for first-line treatment of patients with BRCA1/2-nonmutated advanced epithelial OC (EOC). Methods: Patients with stage III or IV BRCA-nonmutated EOC, primary peritoneal cancer, or fallopian tube cancer will be stratified by surgery status (no residual tumor after primary debulking surgery [PDS], residual tumor after PDS, or planned interval debulking), bevacizumab use, and PD-L1 status (combined positive score < 10 or ≥10). After one lead-in cycle of CT, patients will be randomized 1:1:1 to receive: CT + pembro followed by olaparib maintenance; CT + pembro followed by placebo; or CT + placebo followed by placebo. The CT regimen will be administered for 5 cycles, and pembro 200 mg Q3W will be administered for 35 infusions. Olaparib 300 mg BID maintenance therapy will start after the end of CT as concomitant treatment with pembro until discontinuation or for 2 years if the patient has a complete response. Bevacizumab use is permitted at investigator’s discretion and determined prerandomization. Primary endpoints are investigator-assessed progression-free survival (PFS) per RECIST 1.1 criteria and overall survival. Key secondary endpoints are PFS per RECIST 1.1 assessed by blinded independent central review, PFS after next-line treatment, and safety. Enrollment is currently ongoing. Clinical trial information: NCT03740165.