bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and rationale of MASTERKEY-115 phase II trial of talimogene laherparepvec (T-VEC) with pembrolizumab (pembro) in patients with advanced melanoma who progressed on prior anti-programmed cell death-1 (anti-PD-1) therapy.
Authors: Chesney Jason Alan , Milhem Mohammed M. , Chaney Marya F. , Gokani Priya , Snyder Wendy , Robert Caroline 
Published: May 2020

TPS10079 Background: Treatment options are limited for patients with advanced metastatic or unresectable melanoma, especially after anti-PD-1 failure. T-VEC is an intralesional oncolytic viral immunotherapy designed to selectively replicate in tumor cells and induce local and systemic antitumor response. Pembro promotes T cell activity by blocking PD-1 receptors. Combining T-VEC and pembro may produce robust antitumor activity by increasing T cell activation and blocking T cell inhibition, with a tolerable safety profile. The MASTERKEY-115 trial will evaluate safety and efficacy of T-VEC combined with pembro in patients with advanced melanoma who experienced progressive disease (PD) on prior anti-PD-1 therapy. Methods: NCT04068181 is a phase 2, open-label, single-arm, multicenter trial of T-VEC with pembro in patients with advanced melanoma and PD on prior anti-PD-1. The study is expected to enroll approximately 100 patients and comprises 4 cohorts. Cohorts 1 and 2 will receive anti-PD-1 in a locally recurrent or metastatic setting and experienced PD within 12 weeks of the last anti-PD-1 dose (Cohort 1: PD or stable disease prior to confirmed PD; Cohort 2: complete or partial response prior to confirmed PD). Cohorts 3 and 4 will receive adjuvant anti-PD-1 and were disease-free for < 6 months (Cohort 3) or ≥ 6 months (Cohort 4) prior to confirmed PD. Enrollment criteria include adults with histologically confirmed unresectable or metastatic stage IIIB–IVM1d melanoma, measurable and injectable disease, ECOG PS 0-1, and prior anti-PD-1 (≥ 2-3 consecutive cycles within 8 weeks, immediate prior treatment before enrollment). The primary endpoint is objective response rate per modified RECIST. Key secondary endpoints assess efficacy (objective response rate, best overall response, complete response rate, response duration, durable response rate, disease control rate, progression-free survival, overall survival), safety (incidence of treatment-emergent and treatment-related adverse events, abnormal laboratory tests), and time to subsequent anticancer therapy. The study began enrolling patients in January 2020 and enrollment is ongoing. Clinical trial information: NCT04068181.
A phase I study of Aurora kinase A inhibitor LY3295668 erbumine as a single agent and in combination in patients with relapsed/refractory neuroblastoma.
Authors: DuBois Steven G. , Kremer Jill D. , De Wilde Bram , Jacobsen Chad , Aerts Isabelle , Mosse Yael P. , Maris John M. , Lithio Andrew , Gosberg Andreas , Banks C.L. , Tate Courtney , Dowless Michele , Gong Xueqian , Stancato Louis , Bell-McGuinn Katherine M. , Park Julie R. , Pearson Andrew DJ , Marachelian Araz 
Published: May 2020

TPS10561 Background: Aurora kinase A (AurA) has been implicated in high-risk neuroblastoma, including roles stabilizing and increasing expression of MYCN protein. AurA impacts the function of MYCN in mediating transcription in a cell cycle dependent manner, suggesting that neuroblastoma and other MYC/MYCN-driven tumors may be sensitive to AurA inhibition. LY3295668 is a selective AurA inhibitor. The lack of AurB inhibitory activity is hypothesized to minimize on-target hematologic toxicity associated with AurB inhibition. The molecule’s selectivity is intended to allow for continuous dosing at exposures associated with > 90% target inhibition at trough. In an analysis of LY3295668 antiproliferative effects in 560 cancer cell lines, neuroblastoma was among the most sensitive histologies tested. This screen also separately evaluated genomic predictors of response to LY3295668, with MYC/ MYCN amplification identified as among the strongest predictors of sensitivity to this agent. LY3295668 is currently being evaluated in early phase adult trials. The current trial (J10-MC-JZHD) was uniquely designed to hasten time to first-in-child oncology development for a rare unmet need of relapsed/refractory neuroblastoma patients. Methods: Study J1O-MC-JZHD (NCT04106219) is a multicenter, dual collaboration (NANT and ITCC), randomized, open-label, Phase 1 study of oral LY3295668 in children with relapsed/refractory neuroblastoma. A rolling 6 design will be followed for dose escalation in both a monotherapy cohort and a combination cohort testing LY3295668 together with cyclophosphamide and topotecan. The starting monotherapy dose will be equivalent to 80% of the adult maximum tolerated dose. Key eligibility criteria include recurrent/refractory neuroblastoma not amenable to curative treatment, age 2-21 years, mandatory archival tissue submission, ability to swallow capsules, and adequate hematologic and organ function. LY3295668 is administered in capsule form orally BID continuously. Primary objectives include assessments of safety and tolerability of study drug to identify RP2D as monotherapy and combination, and assess antitumor activity. Secondary objectives include assessment of the pharmacokinetic profile as monotherapy and in combination, and assessment of the relationship between study drug exposure and efficacy. Following determination of the RP2Ds, an expansion phase will randomize patients to monotherapy or to the combination arm. Enrollment began 16 Dec 2019 and is ongoing. Clinical trial information: NCT04106219.
A phase II trial of nivolumab (NIVO) + palbociclib (PAL) + anastrozole (ANA) in postmenopausal women and men with estrogen receptor (ER)+/human epidermal growth factor 2 (HER2)- primary breast cancer (BC): CheckMate 7A8.
Authors: Tolaney Sara M. , Jerusalem Guy , Salgado Roberto , Liu Xiaochun , Chen Tian , Zhang Hongxia , Roberts Mustimbo , Zardavas Dimitrios , Prat Aleix 
Published: May 2020

TPS1105 Background: Cyclin-dependent kinase 4/6 (CDK 4/6) inhibition coupled with ER signaling blockade is an efficient treatment approach for patients (pts) with metastatic hormone receptor-positive, HER2− BC. Preclinical data suggest synergistic activity of CDK 4/6 inhibition and PD-1 blockade; in a syngeneic mouse tumor model, improved efficacy and complete tumor regression were observed with phased administration of ABE + PD-L1 therapy. Methods: CheckMate 7A8 (NCT04075604) is a randomized, noncomparative, multicenter, phase 2 study evaluating PAL + ANA +/- NIVO in postmenopausal pts with ER+, HER2− primary BC. After determining safe doses for NIVO combination regimens in the safety run-in phase, pts will be randomized in a 4:4:3 ratio to 1 of 3 treatment arms (Table) stratified by PD-L1 expression, node status and tumor size. Following treatment, all pts will undergo surgery and safety follow-up. Eligible pts are postmenopausal women and men with newly diagnosed, untreated, histologically confirmed ER+, HER2− BC with primary tumor ≥ 2 cm; suitable for neoadjuvant endocrine monotherapy and surgery; ECOG PS of 0–1; have baseline tumor tissue available; willing to undergo on-treatment research biopsy and tissue collection at surgery. Primary endpoints are number of pts with occurrence of dose-limiting toxicity (safety run-in phase) and residual cancer burden 0–I rate by central assessment at time of definitive surgery (randomized phase). Secondary endpoints include safety and tolerability, pathologic complete response, objective response rate and breast-conserving surgery rate. Key exploratory endpoints include biomarkers indicative of pharmacodynamic changes and potentially predicting treatment sensitivity. Interim analyses are planned. The study is currently enrolling. Clinical trial information: NCT04075604 . [Table: see text]
[OPTIMAL 3] A phase III trial to evaluate the efficacy and safety of DHP107 (Liporaxel, oral paclitaxel) compared to Taxol (IV paclitaxel) as first line therapy in patients with recurrent or metastatic HER2 negative breast cancer (BC) (NCT03315364).
Authors: Kim Sung-Bae , Zhang Qingyuan , Sun Tao , Seo Jae Hong , Lee Keun Seok , Kim Tae-Yong , Tong Zhongsheng , Park Kyong Hwa , Moon Yong Wha , Wang Shusen , Li Wei , Yang Yaewon , Wang Jingfen , Wang Xian , Choi Jonggwon , Lee Ji Eun , Yoon Koung Eun , Chung Seongwuen , Xu Binghe , Sohn Joohyuk 
Published: May 2020

TPS1106 Background: Paclitaxel is a microtubule-stabilizing drug used for various cancers including breast cancer (BC) and gastric cancer (GC). DHP107 is an oral paclitaxel solution formulated with non-toxic excipients using DH-LASED technology, which doesn’t require pre-treatment. DHP107 demonstrated comparable efficacy and safety to IV paclitaxel for patients with advanced GC (Ann Oncol 2018), and was market approved as the first oral paclitaxel in 2016 for GC in Korea. In previous OPTIMAL phase II study, the primary endpoint objective response rate (ORR) was 54.5% in HER2 negative metastatic BC (MBC) patients and 44.4% in triple negative BC (TNBC) patients. Disease control rate (DCR) was 90.9% by the investigators’ assessment. Toxicity was manageable (2019 ESMO). OPTIMAL phase III is being conducted in Korea, China and Eastern Europe based on this result and another phase II study (OPERA) is being performed in USA. Methods: OPTIMAL 3 study is a multinational, multi-center, randomized and open-label trial enrolling HER2 negative (HR+/HER2- or TNBC) recurrent or metastatic BC patients. Patients are randomized to either study (DHP107) or control group (IV paclitaxel) in a 1:1 ratio and stratified by disease free interval (DFI≤48 weeks vs >48 weeks), visceral metastasis status (visceral vs non-visceral) and country. Patients are administrated with DHP107 (200mg/m2 p.o. bid) or IV paclitaxel (80mg/m2 infused) on D1, 8, 15, q4wks. Tumor assessments are performed on every 8 weeks (±7 days) from C1D1 until disease progression (RECIST V1.1). Key inclusion & exclusion criteria are hormone receptor (ER/PR) positive or negative, HER2 negative, ECOG performance status ≤1 and no prior chemotherapy in recurrent or metastatic disease. The primary endpoint is progression free survival (PFS). Secondary endpoints include ORR, overall survival (OS), time to treatment failure (TTF), DCR, quality of life (QoL) and safety. Total target number of patients is 476 with an estimated 10% drop-out rate. The test is based on non-inferiority hypothesis (HR=1.33) with 80% power. The primary endpoint will be analyzed using a one-sided test at a 2.5% significance level, and other endpoints will be analyzed using a two-sided test at a 5% significance level, with 95% confidence interval. The first subject was enrolled in Jan 2019 and recruitment is ongoing and is expected to be completed in Dec 2020. Final results of this study will be announced by the end of 2022. Clinical trial information: NCT03315364 .
CONTESSA TRIO: A multinational, multicenter, phase (P) II study of tesetaxel (T) plus three different PD-(L)1 inhibitors in patients (Pts) with metastatic triple-negative breast cancer (TNBC) and tesetaxel monotherapy in elderly pts with HER2-metastatic breast cancer (MBC).
Authors: Tolaney Sara M. , Bondarenko Igor , Chan Arlene , Dacosta Noshir Anthony , Izarzugaza Yann , Kim Gun Min , Liu Mei-Ching , Perez Maria EVA , Lu Yen-Shen , Oliveira Mafalda , Ow Samuel Guan Wei , Pavic Michel , Rugo Hope S. , Schwartzberg Lee S. , Stradella Agostina , Tan Tira Jing Ying , Wright-Browne Vance , O'Connell Joseph P. , Wei Thomas , Mittendorf Elizabeth A. 
Published: May 2020

TPS1111 Background: Chemotherapy treatments with robust efficacy that preserve quality of life are needed. T is a novel, oral taxane that has potential advantages over currently available taxanes, including: oral administration with a low pill burden and once every 3 week (Q3W) dosing; no observed hypersensitivity reactions; preclinical evidence of central nervous system (CNS) penetration; and improved activity against chemotherapy-resistant tumors. More than 600 pts have been treated with T in clinical studies. T had robust monotherapy activity in a P2 study in 38 pts with HER2-, HR+ MBC, with a confirmed objective response rate (ORR) per RECIST 1.1 of 45%. Methods: CONTESSA TRIO is a 2-cohort, multinational, multicenter, P2 study. In Cohort 1, 90 pts (potential expansion to up to 150 pts) with metastatic TNBC who have not received prior chemotherapy for advanced disease will be randomized 1:1:1 to receive T at 27 mg/m2 Q3W plus either: (1) nivolumab at 360 mg Q3W; (2) pembrolizumab at 200 mg Q3W; or (3) atezolizumab at 1,200 mg Q3W. Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are approved for the treatment of multiple types of cancer; atezolizumab, in combination with nab-paclitaxel, was recently approved in the US for the treatment of metastatic TNBC. The dual primary endpoints for Cohort 1 are ORR and progression-free survival (PFS). A sample size of 30 pts in each PD-(L)1 inhibitor treatment group has approximately 70% power to detect an ORR difference of ≥ 35% between the treatment group with the highest ORR and the treatment group with the lowest ORR. Secondary endpoints include duration of response (DoR) and overall survival (OS). Efficacy results for each of the 3 PD-(L)1 inhibitor combinations will be assessed for correlation with the results of each of the 3 approved PD-L1 diagnostic assays. CONTESSA TRIO is the first randomized clinical study to compare 3 approved PD-(L)1 inhibitors. In Cohort 2, 40 elderly pts (potential expansion to up to 60 pts) with HER2- MBC who have not received prior chemotherapy for advanced disease will receive T monotherapy at 27 mg/m2 Q3W. The primary endpoint for Cohort 2 is ORR. A sample size of 40 will allow the ORR to be estimated with a maximum standard error of < 8%. Secondary endpoints include PFS, DoR and OS. Pts with CNS metastases are eligible for both cohorts. The study was initiated in March 2019. Clinical trial information: NCT03952325 .
NCI protocol 10250: A phase II study of temozolomide and olaparib for the treatment of advanced uterine leiomyosarcoma.
Authors: Ingham Matthew , Allred Jacob B , Gano Katherine , George Suzanne , Attia Steven , Burgess Melissa Amber , Boikos Sosipatros Alexandros , Bui Nam , Chen James Lin , Close Julia Lee , Seetharam Mahesh , Thaker Premal H. , Schwartz Gary K. 
Published: May 2020

TPS11570 Background: Soft tissue sarcoma (STS) is a heterogenous malignancy of mesenchymal origin and includes more than 50 biologically distinct subtypes. Leiomyosarcoma (LMS), a neoplasm of smooth muscle origin, represents up to 20% of STS. The uterus is the most common site of origin in women. Advanced uterine LMS (uLMS) is initially treated with gemcitabine + docetaxel or anthracycline-based chemotherapy but overall survival remains < 24 mos. Besides recurrent alterations in RB1, TP53 and ATRX, insight into cancer biology of uLMS remains limited. Recently, whole exome and transcriptomic sequencing studies suggest uLMS harbors characteristic defects in the homologous recombination (HR) DNA repair pathway and thus features of BRCAness. HR-deficient cancers are unable to efficiently repair double-stranded DNA breaks and appear sensitive to treatment with poly ADP-ribose polymerase (PARP) inhibitors. In preclinical studies, the combination of temozolomide (T), an alkylating agent, and olaparib (O), a PARP inhibitor, was synergistic and markedly suppressed proliferation of uLMS models. A recent phase II study in small cell lung cancer defined the RP2D for T + O where the chief toxicity was myelosuppression. Methods: NCI Protocol #10250 is a single-arm, open-label, multi-center phase II clinical trial of T + O in patients with advanced uLMS. Eligible pts have ECOG PS ≤ 2, progression on ≥ 1 prior line of therapy and disease measurable by RECIST v1.1 and amenable to image-guided biopsy. Pts receive T 75 mg/m2 PO daily + O 200 mg PO BID on days 1-7 in 21-day cycles. The 1° endpoint is objective response rate (ORR). A one-stage binomial design is used to evaluate for an ORR ≤ 10% (null hypothesis) versus ≥ 35% (alternative hypothesis). The design calls for 22 patients. If 5/22 respond, the treatment is promising. This design yields 93% power and 1-sided type I error of 6%. 2° endpoints include progression free survival and safety. All pts undergo tumor biopsies pre-treatment and during cycle 2. Tissue is used for correlative analysis interrogating uLMS for features of BRCAness through (a) whole exome sequencing/RNAseq to evaluate for alterations in HR pathway component genes, (b) RAD51 foci formation by immunohistochemistry as a functional marker of HR pathway activity and (c) protein expression of Schlafen family member number 11 (SLFN11), an emerging biomarker for PARPi. Tumors are also evaluated for MGMT protein expression, a known determinant of sensitivity to T. The study opened to accrual 10/2019. Clinical trial information: NCT03880019.
The effect of longitudinal exercise programming in breast cancer patients.
Authors: Fukui Jami Aya , Cheng Shirley , Lim Shannon , Shepherd John , Yamada Paulette , Teranishi-Hashimoto Cheri 
Published: May 2020

TPS12124 Background: Obesity and weight gain are significant concerns for breast cancer survivors. Obesity at diagnosis is an established negative prognostic factor and studies suggest that post-diagnosis weight gain may increase risk for recurrence and decrease disease free survival. Various interventions such as dietary modification, physical activity, individualized counseling, cognitive behavioral therapy, and combinations of these interventions have been studied in order to identify strategies for weight loss in breast cancer survivors. However, one of the main challenges have been to show sustainability in these interventions. Given the adverse consequences of weight gain after diagnosis, continued efforts to identify appropriate weight management interventions aimed at promoting overall health and long term survivorship are needed. Methods: We have opened an investigator initiated Breast Cancer Exercise Study that provides a tailored exercise program and body health assessments for breast cancer patients along their treatment journey. We are enrolling women diagnosed with breast cancer up to 2 years after their diagnosis into a two 12-week exercise program. Participants’ biometrics and physical assessments will be assessed at baseline to determine the appropriate exercise intensity to implement. Women will attend private 1:1, 90min sessions, 3 days/week. At the end of the initial 12-week program, biometric assessments are again performed and participants are then randomized to either: a) continue with individual exercise classes, 2 days/week or b) continue with group exercise classes, 2 days/week. The study follows their long term outcomes including cancer recurrence, exercise adherence as well as quality of life symptoms. The functional health assessment and subsequent personalized exercise program utilizes kinesiology students from University of Hawaii-Manoa during their clinical practicum and is based at our community partner facility the Rehabilitation Hospital of the Pacific. Body assessments and other biomarkers are evaluated through expertise at University of Hawaii Cancer Center. Collectively, our study exemplifies our partnership with community facilities, utilizes cutting edge research and incorporates local students, to provide an important health program for cancer patients all the while enriching our understanding of the unique patient population. The results of this project may help to develop standardized exercise protocols for breast cancer survivors and provide insights to other important health concerns. Clinical trial information: NCT04013568 .
Phase III TRIDENT trial: Radiation and temozolomide +/- tumor treating fields in newly diagnosed glioblastoma.
Authors: Shi Wenyin , Kleinberg Lawrence , Jeyapalan Suriya A. , Goldlust Samuel Aaron , Nagpal Seema , Reardon David A. , Combs Stephanie E , Roberge David , Nishigawa Ryo , Glas Martin 
Published: May 2020

TPS2580 Background: Tumor treating fields (TTFields) is a non-invasive, regional antimitotic treatment approved as a standard of care for glioblastoma (GBM). In the EF-14 phase III trial, TTFields (200 kHz) plus temozolomide (TMZ) significantly increased the survival of patients with newly diagnosed GBM (ndGBM) without increase in systemic toxicity. TTFields-related AEs were mainly skin AEs. In preclinical models, TTFields increase the therapeutic effects of radiation therapy (RT). A pilot study showed that TTFields concomitant with RT and TMZ is well tolerated. The benefit of concomitant TTFields with RT and TMZ will be tested in this phase III TRIDENT randomized trial. Methods: TRIDENT is an international phase III randomized trial comparing standard RT with TMZ vs the triple combination of RT plus TMZ with concomitant TTFields. RT is delivered through the TTFields arrays. Patients in both arms will receive maintenance TTFields with TMZ. TTFields (200 KHz) will be delivered >18 hours/day using Optune. Patients will continue TTFields treatment until second recurrence. Patients with pathologically confirmed newly ndGBM, ≥ 18 years, KPS ≥ 70, either sex, post-surgery or biopsy, who are amenable for RT/TMZ therapy will be enrolled. Patients will be stratified by extent of resection and MGMT promoter methylation status. The primary endpoint is overall survival (OS). Secondary end points include: progression free survival (PFS; RANO), 1- and 2-year survival rates, overall radiological response (ORR; RANO), progression-free survival (PFS2, PFS6, PFS12); severity and frequency of AEs (CTCAE V5.0); pathological changes in resected GBM tumors post treatment; quality of life (EORTC QLQ-C30); and correlation of OS to TTFields compliance. The hypothesis is that concomitant TTFields with radiation and TMZ will significantly improve OS as compared to radiation and TMZ alone. The sample size is 950, with 475 in each arm to detect a HR <0.8 with a 5% type I error. Survival will be measured from the time of randomization until date of death. At the time of analysis, patients who are lost to follow-up or still on protocol follow-up will be censored at the last date known to be alive.