bluuebunny/crossref_metadata_2025_split huggingface dataset:
FLEX, the 30,000 breast cancer transcriptome project: A platform for early breast cancer research using full-genome arrays paired with clinical data.
Authors: Ma Cynthia X. , Whitworth Pat W. , Vukelja Svetislava J. , Gray Carl R. , Diab Sami , Crozier Jennifer , Berrocal Julian , Habibi Mehran , Brufsky Adam , Maganini Robert , Srkalovic Gordan , Bupathi Manojkumar , Feinstein Trevor , O'Shaughnessy Joyce , Barone Julie , Rehmus Esther Hoogland , Lee Laura A. , Nguyen Holly , Blumencranz Lisa Eileen , Audeh M. William ,   FLEX Investigators Group
Published: June 2022

TPS612 Background: The ongoing, multi-center FLEX trial (NCT03053193) began in the United States in 2017, with the ultimate goal of 30,000 patients enrolled. The primary objective is to create a large-scale collaborative registry of early-stage breast cancer patients that links comprehensive clinical and full genome expression data to reveal new prognostic and/or predictive gene signatures. A key secondary objective of the trial is to enable investigator-initiated studies to explore early-stage breast cancer at a relatively low cost to the investigator. Methods: The prospective FLEX trial enrolls patients aged ≥ 18 years with histologically proven stage I-III breast cancer, with negative or 1-3 positive lymph nodes. Eligible patients have received MammaPrint, with or without BluePrint testing as standard of care, and consent to clinically annotated full transcriptome data collection. The FLEX base study protocol permits investigators to submit their own concept proposal, and upon review and approval by the Research and Scientific Review Committees, investigators interrogate clinical and genomic data from the FLEX database. The 10-year enrollment goal is a minimum of 30,000 patients. Since April 2017, 9,170 patients have been enrolled at over 109 sites in the United States. To date, 38 investigator-initiated substudies have been approved and are in progress, and 28 abstracts have been published in the US scientific congresses. To ensure inclusion of diverse populations, patients from local communities and 11 National Cancer Institute-designated Comprehensive Cancer Centers were included. Our diverse data set is helping meet the needs of historically under-represented patients with breast cancer. Of the self-reported ethnicities within the FLEX database, 65% are White or Caucasian, 8% Black or African American, 4% Latin American, and 2% Asian. There are 5 ongoing FLEX sub studies investigating racial disparities. The molecular profiling and differential gene expression analysis in early-stage breast cancer patients of African American, Asian, Hispanic ancestries helps to provide critical insights that correlate tumor biology with treatment outcomes. FLEX is expanding globally with sites anticipated in multiple European countries. The FLEX trial continues to expedite the discovery and development of novel genomic profiles, bringing precision oncology into the clinic to improve breast cancer management. Clinical trial information: NCT03053193.
A single-arm, phase 2 study of perioperative ipilimumab, nivolumab, and cryoablation in women with hormone receptor-negative, HER2-negative, early-stage/resectable breast cancer.
Authors: McArthur Heather L. , Comen Elizabeth Anne , Bryce Yolanda , Solomon Stephen Barnett , Leal Jorge Henrique S. , Abaya Christina DiLauro , Martinez Cristal , Basho Reva K , Park Dorothy J. , McAndrew Philomena , Larkin Brigid , Mills William , Page David B. , Mellinger Staci L. , Fredrich Nicole , Moxon Nicole , Reddy Sangeetha M. , Carter Meredith , Patil Sujata , Norton Larry 
Published: June 2022

TPS617 Background: Local tumor destruction with cryoablation (cryo) induces inflammation and releases antigens that can activate tumor-specific immune responses. Pre-clinically, cryo with checkpoint inhibition augmented tumor-specific immune responses and prevented recurrence. Clinically, we established that peri-operative (peri-op) cryo with ipilimumab (ipi) +/- nivolumab (nivo) was not only safe in patients (pts) with operable, early stage breast cancer (ESBC) but also generated robust intra-tumoral and systemic immune responses. In this phase 2 study, we evaluate the disease specific impact of peri-op ipi/nivo/cryo in women with residual triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC), a subset at high risk of early relapse. Methods: Eligible pts are ≥18y, with ER < 10%, PR < 10%, HER2 negative (per ASCO/CAP definition), ≥ 1.0 cm, residual operable disease after taxane-based NAC. Approximately 80 pts will be enrolled and treated with ipi/nivo/cryo followed by breast surgery and adjuvant nivo. Pts undergo percutaneous, image-guided cryo with concurrent research core biopsy 7-10 days prior to surgery and will receive ipi (1mg/kg IV) with nivo (240mg IV) 1 to 5 days prior to cryo. After surgery, pts will receive 3 additional doses of nivo at 240mg IV Q2 weeks. Adjuvant capecitabine is recommended for all patients per local standard-of-care. Patients will be stratified by NAC platinum administration, NAC anthracycline administration, and clinical nodal status (positive versus negative). The primary endpoint is 3-year Event Free Survival (EFS). Secondary endpoints include Invasive Disease-Free Survival (IDFS), Distant Disease-Free Survival (DDFS), overall survival (OS) and safety. Exploratory correlative studies will be performed on tumor and serum to characterize the immunologic impact of the intervention and to explore predictors of efficacy and toxicity. Clinical trial information: NCT03546686.
A randomized study to measure and enhance the health-related quality of life in patients with cancer receiving immune checkpoint modulators (ME-Q).
Authors: Fonseca Magalhaes Filho Marcos Aurelio , VOON PEI JYE , Carlsson Lindsay , Silver Grace , Hansen Aaron Richard 
Published: June 2022

TPS6603 Background: Existing data demonstrate the impact of Immune checkpoint modulators (ICMs) on Health-Related Quality of Life (HRQOL), but this was from studies that used HRQOL tools developed for patients treated with chemotherapy and/or radiation. To address this gap, we developed a toxicity subscale to cover important immune-related adverse events (irAEs) to combine this subscale with the generic FACT-G to measure HRQOL in patients treated with ICMs, the FACT-ICM. This trial proposes to validate the use of the FACT-ICM as a tool for HRQOL measurement and simultaneously to assess the benefit of remote symptom monitoring and management using a new electronic platform developed specifically for patients receiving ICMs. Methods: Participants will be randomized (1:1) before starting their standard of care ICM therapy to either usual care or the monitoring arm. The ME-Q platform uses a web-based application to enable remote monitoring of patient symptoms and HRQOL, allowing all participants enrolled in both the usual care or monitoring arms to complete the FACT-ICM and other questionnaires (DART, Health Resource Utilization, Decision regret scale, post-study system usability questionnaire) at set time points. Patients on the monitoring arm will have their electronic responses sent automatically, and new or significant worsening symptoms of clinical concern will generate an alert to the advanced practicing nurse (APN) responsible for replying to the patient and acting on responses. Via phone or a video teleconference, the nurse will perform a targeted assessment and provide standardized clinical advice and interventions based on well-established clinical algorithms and international guidelines for the management of irAEs. The APN will inform the patient's clinical team about the patient's responses and obtain the treating team's input and agreement on a proposed treatment plan. Patients enrolled in the usual care arm will respond to the questionnaires; however, their responses are not transmitted to their clinical team. The primary objective will be to validate the PRO tool for HRQOL measurement, and the secondary objective is to improve HRQOL in cancer patients receiving ICMs by remote monitoring and symptom management using the ME-Q electronic platform. We estimate that a total sample size of 266 patients (divided into two arms) achieves 90% power to detect an effect size of 0.4 in mean score changes (from baseline to 4 months) between arms using a two-sample t-test with a two-sided significance level of 0.05. Enrolment is to be completed in 2 years.
Assessment of adolescent and young adult oncology patient and provider perspectives in Philadelphia (AYA-4P).
Authors: Terry Christopher , Pomerantz Miriam , Sandos Jodi , Wilde Lindsay 
Published: June 2022

TPS6604 Background: The overall cancer incidence continues to increase in adolescent and young adult patients (AYAs), defined by the National Cancer Institute as individuals diagnosed between the ages of 15-39. Both disease biology and psychosocial needs are unique for young adults living with cancer. AYAs are more likely to have challenges related to work, insurance, relationships, fertility and emotional distress. Studies demonstrate that specialized supportive care improves outcomes such as health-related quality of life, mental health, and physical functioning. Most AYA oncology programs are developed without patient input and affiliated with pediatrics. The Sidney Kimmel Cancer Center (SKCC) at Jefferson is an adult oncology group serving over 900 new patients annually between the ages of 18-39, but does not have a formal AYA program. With guidance from patient advocates and other validated tools, a unique survey-based needs assessment was created by SKCC to provide data for the development of a comprehensive, patient-centered model of care for AYAs. Methods: A one-time survey will be administered electronically to participants through Qualtrics. Solicitation from SKCC and the Young Adult Cancer Connection, a local patient advocacy group, will occur via social media and email aggregation. Eligible patients are those who received the majority of their cancer care within 30 miles of Philadelphia between the ages of 18-39. Eligible healthcare providers include current advanced practice providers or physicians who have practiced at SKCC for at least 1 year. There are no hypotheses being tested or primary outcome variables, therefore no sample size calculations were performed. A $10 Amazon card is offered as incentive for the patient-directed survey to improve response rates and reach at least 100 completed surveys. The provider survey includes no completion incentive. Each survey should take no longer than 20 minutes to complete and no follow-up is required. Surveys are multiple choice with a single open-ended, free response question at the end for additional comments. Categorical survey responses will be summarized using frequencies and percentages. Descriptive statistics and data visualization will be used to characterize the patient demographics and summarize awareness, experiences, and priorities of the participants. Primary objectives of the surveys are to assess AYAs’ current perspective of age-specific medical services and psychosocial support in Philadelphia, as well as to assess the knowledge and perspective of providers of the current care and available services for AYAs at SKCC. The secondary objective is to identify patient preferences and areas for improvement. By using the data generated from the surveys, SKCC will be more informed in their patient-centric approach to program development in an effort to improve the overall care for Philadelphia’s AYA oncology community.
Phase 1/2, open-label, dose-escalation, dose-expansion study of menin inhibitor DSP-5336 in adult patients with acute leukemia with and without mixed-lineage leukemia (MLL)-rearrangement (r) or nucleophosmin 1 (NPM1) mutation (m).
Authors: Daver Naval Guastad , Affinito John , Cai Hongliang , Dobrowolska Hanna , Eguchi Ken , Zhang Zijing , Stoudemire Jay , Watanabe Akinobu , Martinez Pablo , Komarnitsky Philip 
Published: June 2022

TPS7066 Background: DSP-5336, a menin MLL interaction inhibitor, elicited antitumor activity in MLL–r or NPM1m acute leukemia models in vitro and in vivo. An open-label, single-arm, phase 1/2 study (NCT04988555) will evaluate the safety and efficacy of DSP-5336 and determine the recommended phase 2 dose (RP2D) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL). Methods: Patients aged ≥18 y with R/R AML, ALL, or acute leukemia of ambiguous lineage after ≥1 line of standard therapy, ECOG PS 0–2, and adequate organ function are eligible. Patients will receive DSP-5336 twice daily for 28 d/cycle. In phase 1, there will be two parallel escalation cohorts: patients who do not receive concomitant azole antifungal medication and patients who receive antifungal azoles (ie, posaconazole, voriconazole, or fluconazole); 21–30 patients will be enrolled during phase 1 into multiple ascending dose levels. Dose escalation will use a Bayesian logistic regression model. Phase 2 will enroll two arms: R/R AML with MLL –r and R/R AML with NPM1m (10 –20 patients/arm). Patients will be treated at the RP2D to evaluate clinical activity and safety. Clinical trial information: NCT04988555. [Table: see text]
A phase 1/2 study of REGN5093-M114, a METxMET antibody-drug conjugate, in patients with mesenchymal epithelial transition factor (MET)-overexpressing NSCLC.
Authors: Drilon Alexander E. , Awad Mark M. , Gadgeel Shirish M. , Villaruz Liza C , Sabari Joshua K. , Perez Javier , Daly Christopher , Patel Shraddha , Li Siyu , Seebach Frank A. , Lowy Israel , Magnan Heather D. , Rietschel Petra 
Published: June 2022

TPS8593 Background: MET, also called hepatocyte growth factor receptor (HGFR), is a high-affinity transmembrane protein receptor for HGF. MET is overexpressed in various malignancies, including non-small cell lung cancer (NSCLC). MET overexpression can accompany MET exon 14 alteration or de novo/acquired MET amplification. REGN5093-M114 is an antibody drug conjugate composed of a novel linker-payload (M114, carrying the maytansine derivative M24, a potent inhibitor of microtubule assembly) covalently bound to lysine residues on a MET-targeting human IgG4p bispecific antibody, REGN5093. In preclinical models of MET overexpressing cancers, REGN5093-M114 demonstrated significant dose-dependent antitumor activity. Methods: This is an open label, phase 1/2, first-in-human, multicenter dose-escalation study with cohort expansion evaluating REGN5093-M114 in patients with MET-overexpressing NSCLC (NCT04982224). Patients must have advanced stage NSCLC for which there are no approved therapies available expected to confer clinical benefit, with tumor overexpressing MET (≥75% tumor cell staining at 2+) as centrally confirmed by immunohistochemistry. For the expansion phase, patients must have at least one lesion that is measurable by RECIST 1.1. REGN5093-M114 will be administered intravenously once every 3 weeks over 30 minutes until disease progression, intolerable adverse events, withdrawal of consent, or study withdrawal. The primary objectives in dose escalation are to evaluate safety, tolerability, PK, and maximum tolerated dose and/or recommended phase 2 dosing regimen of REGN5093-M114. PKs will include the assessment of REGN5093-M114, total antibody, and payload M24 concentrations. The primary objective in dose expansion is to assess preliminary anti-tumor activity of REGN5093-M114 in MET-overexpressing NSCLC as measured by the objective response rate. The secondary objectives of both phases of the study include an evaluation of treatment durability, and the immunogenicity of REGN5093-M114. This study is currently open to enrollment. Clinical trial information: NCT04982224.
Phase 2 study of tarlatamab, a DLL3-targeting, half life–extended, bispecific T-cell engager (HLE BiTE)immuno-oncology therapy, in relapsed/refractory small cell lung cancer (SCLC).
Authors: Ramalingam Suresh S. , Ahn Myung-Ju , Akamatsu Hiroaki , Blackhall Fiona Helen , Borghaei Hossein , Hummel Horst-Dieter , Johnson Melissa Lynne , Reck Martin , Zhang Yiran , Jandial Danielle , Cheng Sunfa , Paz-Ares Luis G. 
Published: June 2022

TPS8603 Background: SCLC is characterized by rapid growth and early development of metastases. Platinum-based first-line chemotherapy is associated with a high initial response rate; however, disease recurrence is common. Delta-like ligand 3 (DLL3) is a Notch ligand that is upregulated and aberrantly expressed on the cell surface in most SCLC, making it a compelling therapeutic target. Tarlatamab is an HLE BiTE immuno-oncology therapy designed to bind DLL3 on target cancer cells and CD3 on T cells, forming a cytolytic synapse inducing T cell activation and expansion and T cell-dependent killing of tumor cells. Interim results of an ongoing first-in-human study in patients with relapsed/refractory SCLC (NCT03319940) show preliminary evidence for tarlatamab efficacy in pretreated patients with confirmed partial responses in 20% of patients and duration of response of 8.7 months (Owonikoko TK, et al. Abstract 8510. Presented at: ASCO Annual Meeting, June 4–8, 2021; Virtual). Grade ≥ 3 treatment-related AEs (TRAEs) occurred in 27% of patients and TRAEs resulted in discontinuation in 5% of patients. This promising efficacy/safety profile supports further study of tarlatamab in SCLC. Methods: NCT05060016 is a phase 2, open-label study evaluating tarlatamab in patients with relapsed/refractory SCLC after two or more lines of prior treatment. Part 1 is a dose characterization phase in which subjects will be randomized 1:1 to two active doses of tarlatamab. Part 2 will continue enrollment for the selected target dose only based on interim analysis of Part 1. Key eligibility criteria include adults with histologically or cytologically confirmed SCLC whose disease progressed/recurred after two or more lines of prior treatment including at least 1 platinum-based regimen (including a PD-L1 inhibitor, if standard of care, with certain exceptions per protocol), treated brain metastases, ECOG performance status ≤1, and life expectancy ≥ 12 weeks in the opinion of the investigator. The primary endpoint for the primary analysis is ORR per RECIST 1.1 as assessed by blinded independent central review. Secondary objectives are to evaluate antitumor activity by additional measures (duration of response, progression-free survival, disease control rate and duration, overall survival), safety and tolerability, immunogenicity, and pharmacokinetics. Sites in North America, Asia and Europe are participating in the trial with subjects already enrolled and enrollment ongoing. Clinical trial information: NCT05060016.
A biomarker-guided Bayesian response-adaptive phase II trial for metastatic melanoma: The Personalized Immunotherapy Platform (PIP) trial design.
Authors: Lo Serigne N. , Gide Tuba Nur , Gonzalez Maria , Silva Ines , Menzies Alexander M. , Carlino Matteo S. , Scolyer Richard A. , Heritier Stephane , Wilmott James S. , Long Georgina V. 
Published: June 2022

TPS9599 Background: Anti-PD1-based immunotherapies have been approved for many cancer types and are now a standard therapy for advanced melanoma. Despite this, ̃50% of advanced melanoma patients (pts) fail to respond or eventually progress after response. It is therefore critical to identify pts with a low likelihood of response to anti-PD1-based therapy and efficiently assess activity of rationally-selected alternative novel immunotherapies. Methods: We designed this investigator-initiated phase II PIP-Trial to evaluate two consecutive biomarker testing platforms, followed by the activity of rationally selected 5 novel agents in pts with advanced melanoma. Two separate pt populations are included: Part-A) treatment-naïve pts predicted to be resistant to either anti-PD-1 alone or combined with ipilimumab using Biomarker Test-1); and Part-B) pts who had progressed on 1 prior line of PD1-based therapy. Part-A) is a Bayesian adaptive multi-arm multi-stage design using response adaptive randomisation after a burn-in period where pts are randomised to the existing arms with equal probability. From then on, regular interim analyses will be carried out with the objective to either drop poorly performing arms or continue. Part-B) is an open platform without control that combined a selection and an expansion phase to identify best novel agent(s) as second-line therapy. Expansion phase decisions will be based on enrichment for biomarker Test-2. Dropping an arm occurs when the posterior probability of observing a clinically significant effect on the primary outcome (i.e. 6-month RECIST objective response rate (ORR)) is low. The operational characteristics of the design were investigated through simulations considering 4 plausible scenarios with 40% ORR in the control arm (anti-PD1 + Anti-CTLA4). Simulations were based on the upcoming R package BATS. Part-A has at least 85% power to detect a 30% absolute improvement in ORR with respect to the control arm (with a max N = 216 – Table below). Part-B will be able to select two promising treatments in the expansion phase and formally test their efficacy against a minimum ORR of 25% at 80% power (max N = 150). [Table: see text]
Reliability of Drug History to Verify Androgen Abuse in Men
Authors: Shankara-Narayana Nandini , Brooker Lance , Goebel Catrin , Speers Naomi , Handelsman David J 
Published: June 2022

Abstract

Context
Clinical evaluations that require excluding androgen abuse, a secretive, illicit activity, rely on the drug history, but its veracity for androgen abuse has neither been verified nor has any objective corroborating laboratory test been validated.

Objective
In a high-risk population, to (a) validate the drug history of androgen abuse objectively using state-of-the-art World Anti-Doping Agency–accredited antidoping laboratory urine mass spectrometry tests and (b) to determine what biochemical tests best distinguish androgen abuse from nonuse in this population.

Methods
Urine samples from current (n = 41) and past (n = 31) androgen abusers and nonusers (n = 21) were analyzed by comprehensive mass spectrometry-based detection tests for androgens and related drugs (ARD).

Results
No prohibited ARDs were identified among nonusers. Current users had a median of 5 (range 1-13) drugs detected comprising 176 ARDs among 220 drug identifications. Past users had a median of 1 (range 0-9) drugs detected comprising 21 ARDs among 43 drugs. Negative predictive value was high (&gt;0.8) for those denying drug usage while positive predictive value was good (&gt;0.6) for both those reporting currently using (current) and not using (nonusers plus past users) ARD. Serum luteinizing hormone (LH) alone had high, but imperfect, discriminatory power (89%) to distinguish between current and noncurrent androgen use.

Conclusions
We demonstrates that a negative drug history in a high-risk group has high reliability and that even a single suppressed serum LH exhibits high discrimination for objectively detecting androgen abuse.