bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I/II study of bintrafusp alfa and NHS-IL12 in combination with docetaxel in adults with metastatic castration sensitive (mCSPC) and castration-resistant prostate cancer (mCRPC).
Authors: Atiq Mohammad O. , Bilusic Marijo , Karzai Fatima , Cordes Lisa M. , Strauss Julius , Abdul Sater Houssein , Redman Jason , Floudas Charalampos S. , Hodge James W. , Gameiro Sofia , Figg William Douglas , Schlom Jeffrey , Dahut William L. , Gulley James L. , Madan Ravi Amrit 
Published: June 2021

TPS5096 Background: Immune checkpoint inhibition is successful in a small subpopulation of men with prostate cancer. This could be related to barriers to immune response in the tumor microenvironment. Immunocytokines present an opportunity to specifically target the pleiotropic tumor microenvironment impacting immune cells beyond T-cells. NHS-IL12 is an immunocytokine that carries IL-12 (shown to impact natural killer and myeloid cells) and binds to necrotic tissue with exposed histones. Phase 1 studies have indicated immune and even PSA responses in prostate cancer to NHS-IL12 (Strauss J, CCR 2019). Preclinical data has demonstrated synergy with docetaxel, which is standard therapy in both mCSPC and mCRPC. Further synergy has been shown with a novel first-in-class bifunctional fusion protein (bintrafusp alfa) composed of the extracellular domain of human TGF-β receptor II (TGFβRII), which effectively functions to sequester or “trap” all three TGF-β isoforms (Lind H, JITC 2020), fused to a monoclonal antibody against PD-L1. This study will examine the potential of a novel combination of chemotherapy, checkpoint inhibition, and immunocytokines in metastatic prostate cancer. Methods: The study will evaluate safety of NHS-IL12 with docetaxel at escalating doses followed by the addition of bintrafusp alfa in all metastatic patients. Once safety of the combination is established, patients will enroll in 2 cohorts with either mCSPC or mCRPC. Eligible patients include mCSPC (≤134 days of starting ADT) and mCRPC (must have been previously treated with abiraterone or enzalutamide), with good performance status (ECOG of ≤ 2). Patients with brain metastases or who are immunocompromised are excluded. For mCSPC, the primary endpoint will evaluate the increase in the proportion of patients who have a PSA less than 0.2 ng/mL 7 months after the start of ADT, which is based on the prognostic value of PSA less than 0.2 ng/mL at 7 months in mCSPC (Harshman L, JCO 2017). The secondary endpoint is biochemical and radiographic time to progression. The primary endpoint for the mCRPC patients will evaluate progression free survival with secondary endpoints examining the percentage of patients with a 50% PSA decline from baseline and radiographic response rates per RECIST. Exploratory analysis will analyze changes in immune cell subsets after treatment as well as immune status of the tumor microenvironment. Clinical trial information: NCT04633252.
Identifying androgen receptor (AR) and genomic characteristics that define populations of patients with mHSPC who benefit from early PARP inhibition therapy with talazoparib.
Authors: Kasparian Saro , Burnham Leanne , Kittles Rick , Sun Zj , Bedell Fornati , Tran Justin , Li Min , Dorff Tanya B. 
Published: June 2021

TPS5097 Background: A minority of men with mCRPC, those with DNA repair mutations, can benefit from PARP inhibitor therapy. In addition to DNA repair, PARP is used by cancer cells to interact with other cellular mechanisms including androgen receptors (AR). The next generation PARP inhibitor talazoparib can, in addition to inhibiting DNA repair, trap PARP, preventing it from carrying out its other functions. As progression in mHSPC is based on AR escape mechanisms, we predict that early exposure to PARP inhibition will delay progression. In addition, AR characteristics and function vary by ethnic populations. AR expression is inversely related with the number of polymorphic CAG repeats. As African American (AfrAm) men commonly have shorter CAG repeats in their AR, they may experience different response duration, but have been under-represented in clinical trials. Furthermore, CAG repeats may be associated with greater signaling through pathways such as wnt and Myc, which is associated with aggressive disease. Thus, studying intensified up-front therapy in a diverse prostate cancer population is a critical unmet need. Methods: 70 subjects will be treated with ADT + abiraterone + talazoparib. Outreach by our Division of Health Equities and accrual at community satellites located near diverse populations will be enlisted to accrue a target of 30% African American. Talazoparib will be dosed at 1mg daily (0.75 mg in renal insufficiency). LHRH and abiraterone formulations will be left to physician’s choice. PSA and safety labs will be checked every 4 weeks for the first 12 weeks. Imaging will be performed every 12 weeks for the first year then every 24 weeks if PSA is decreasing, or 12 weeks if rising. Data safety monitoring for toxicity after every 10 subjects have been accrued. Diversity of accrual will be evaluated after 30 subjects are enrolled; amendments will be made if the diversity goal is not achieved. Tissue genomics and ctDNA will be measured at baseline; ctDNA will be repeated after 4 weeks and at castration resistance. Endpoints: Primary: PSA nadir at 7 months has been found to be associated with overall survival and is achieved by 55% of men with mHSPC with ADT + abiraterone. With 70 subjects there is 97% power to confirm improved nadir rate of 75%, and 83% power to determine a nadir rate >70%. Secondary endpoints include objective response by RECIST 1.1 for subjects with measurable disease. radiographic progression free survival. Correlative objectives include comparing outcomes in subsets of men with high vs low number of AR CAG repeats, men with genomic alterations, and the change in ctDNA alteration fractions from baseline to 4 weeks and at progression. Progress: The trial is open to accrual as of Feb 2021. Sponsor: Pfizer/ Prostate Cancer Foundation RFP Clinical trial information: NCT04734730.
A randomized phase III, two-arm trial of paclitaxel, carboplatin, and maintenance letrozole versus letrozole monotherapy in patients with stage II-IV, primary low-grade serous carcinoma of the ovary or peritoneum.
Authors: Nickles Fader Amanda , Gien Lilian Tran , Miller Austin , Covens Al , Gershenson David Marc 
Published: June 2021

TPS5601 Background: Low-grade serous carcinoma of the ovary or peritoneum (LGSOC) is a rare subtype of epithelial carcinoma. Differences in epidemiology, pathogenesis, disease presentation, and clinical outcomes have been characterized between women diagnosed with LGSOC and those with the p53-driven high-grade serous carcinoma (HGSOC). Ultimately, patients with LGSOC should be treated differently than those with HGSOC. Several studies suggest that LGSOC is relatively chemoresistant and that most tumors robustly express estrogen and progesterone receptors. Recently, retrospective reports suggest that utilization of the aromatase inhibitor, letrozole, as monotherapy or in addition to platinum/taxane-based chemotherapy in those with primary advanced-stage LGSOC results in preliminarily promising survival outcomes. Methods: This study is a two-arm, randomized, open-label, Phase III clinical trial. The primary objective is to assess whether letrozole monotherapy (2.5 mg po daily) is non-inferior to carboplatin (AUC 5-6) and paclitaxel (175 mg/m2) followed by letrozole maintenance therapy with respect to progression free survival in women with primary, Stage II-IV LGSOC who have undergone an attempt at maximal surgical cytoreduction. Secondary endpoints include incidence of adverse events, objective response rate in those with measurable disease after surgery, response duration, overall survival, and adherence to letrozole maintenance therapy. Study subjects must have undergone a bilateral salpingo-oophorectomy, and p53 IHC testing of tumors is required to rule out those with aberrant p53 expression commonly observed in HGSOC tumors. Study strata include residual disease status and country of enrollment. Four hundred and fifty patients will be enrolled in the United States, Canada and South Korea through the NRG Oncology trials network. Correlative aims include analyzing the association of ER/PR tumoral expression with aromatase inhibitor therapy response and determining ESR1 mutational status in those who develop letrozole resistance. The study includes two interim analyses; at 20% information time, a futility analysis will be conducted, and at 40% information time, both efficacy and futility will be assessed. This is one of the first randomized trials performed in women with primary, advanced LGSOC, and the study is open with 71 patients enrolled at the time of abstract submission. Clinical trial information: NCT04095364.
ALEXANDRA/IMpassion030: A phase 3 study of standard adjuvant chemotherapy with or without atezolizumab in patients with early-stage triple-negative breast cancer.
Authors: Saji Shigehira , McArthur Heather L. , Ignatiadis Michail , Bailey Andrew , El-Abed Sarra , Brandao Mariana , Metzger Otto , Lai Catherine , Guillaume Sebastien , Fumagalli Debora , Agbor-tarh Dominique , Seiller Aicha , Altarcheh Xifro Rosa , Honvault Vanessa , Viale Giuseppe , DuFrane Carter , Barata Teresa , Winer Eric P. , Gelber Richard D. , Piccart-Gebhart Martine J. 
Published: June 2021

TPS597 Background: Early stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. Because TNBC does not currently have specific targeted agents approved for use in the early setting, it is treated primarily with chemotherapy. TNBC may be more immunogenic than other subtypes of breast cancer. Atezolizumab (an anti–PD-L1 antibody), in combination with nab-paclitaxel has been approved in >70 countries for the treatment of PD-L1-positive unresectable locally advanced or metastatic TNBC based on the results of the randomized phase 3 IMpassion130 trial. The phase 3 IMpassion031 study, evaluating atezolizumab in combination with chemotherapy (nab-paclitaxel followed by doxorubicin and cyclophosphamide) in comparison to placebo plus chemotherapy as neoadjuvant treatment demonstrated a statistically significant and clinically meaningful improvement in pCR in both PD-L1 positive and PD-L1 negative tumors. ALEXANDRA/IMpassion030 is a global, prospective, randomized, open-label, phase 3 trial currently investigating the efficacy, safety and pharmacokinetic profile of adjuvant atezolizumab plus standard anthracycline/taxane adjuvant chemotherapy versus chemotherapy alone in early stage TNBC. Methods: ALEXANDRA/IMpassion030 will randomize 2300 patients with operable stage II-III TNBC, confirmed by central pathology review. Patients are stratified by type of surgery, nodal status, and centrally assessed PD-L1 status. Adjuvant chemotherapy consist of weekly paclitaxel 80 mg/m2 for 12 weeks followed by dose dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks or the same chemotherapy regimen (T-EC/AC) given concomitantly with atezolizumab 840 mg every 2 weeks followed by maintenance atezolizumab 1200 mg every 3 weeks until completion of 1 year of atezolizumab. The primary endpoint is invasive disease-free survival (iDFS) and secondary endpoints include, iDFS in the PD-L1 selected tumour status (IC1/2/3) and node-positive subpopulations, overall survival, safety, patient functioning and health related quality of life (HRQoL). Tumor tissue and blood samples will be collected for biomarker research. The first site was activated on May 4 2018, and approximately 373 sites in 30 countries are currently participating in this trial. This trial is sponsored by F. Hoffmann-La Roche Ltd and conducted in partnership with the Breast International Group, Frontier Science and Technology Research Foundation, Institute Jules Bordet and Alliance Foundation Trials. Clinical trial information: NCT03498716.
V2 Trial: A phase I study of venetoclax and CPX-351 for young patients with relapsed/refractory acute leukemia.
Authors: Agresta Laura , O'Brien Maureen Megan , O'Brien Eric Justin , Norris Robin Elizabeth , Breese Erin Haag , Burns Karen Cristly , Mizukawa Benjamin , Ryan Thomas D , Desai Pankaj B , Vinks A.a. , Grimes H. Leighton , Absalon Michael , Perentesis John Peter 
Published: June 2021

TPS7052 Background: Despite significant advances in therapy for acute myeloid leukemia (AML), 30-40% of young patients will relapse, after which prognosis is poor. In young patients, curative-intent salvage therapy involves intensive re-induction followed by hematopoietic stem cell transplant. Recently, the COG Phase II study of CPX-351 (liposomal cytarabine:daunorubicin, Vyxeos™) in pediatric patients with AML in first relapse (NCT02642965) demonstrated a CR/CRi rate of 81.3%. Separately, our first-in-pediatrics CPX-351 Phase I (NCT01943682) showed 48% in a heavily pre-treated pediatric cohort with multiply relapsed and refractory (R/R) AML. Our integrated pilot study of single cell RNA sequencing (scRNA-seq) done before, during, and after CPX-351 showed p53 targets over time with enrichment for genes regulating apoptosis (ex.: FAS, BAX), suggesting blasts may be primed for apoptosis following CPX-351. Venetoclax is a small molecule inhibitor of the anti-apoptotic protein BCL-2, a regulator of apoptotic balance in some leukemias. Based on our preclinical data, we developed a Phase I study to investigate venetoclax with CPX-351 for the treatment of young patients with R/R acute leukemias. Methods: The V2 Trial (NCT03826992) is a single-institution Phase I study to evaluate the safety and tolerability of venetoclax with CPX-351 in patients ages 1-39 years with R/R acute leukemias. Inclusion diagnoses include AML, mixed phenotype acute leukemia (MPAL), KMT2A-rearranged acute lymphoblastic leukemia (ALL), and T-ALL. Exclusion criteria include CNS status 3, bone marrow failure syndromes, and prior cardiotoxic exposures above acceptable risk thresholds. Subjects receive a single course of CPX-351 at the FDA approved adult dose on Days 1, 3, 5 with concurrent daily venetoclax. In the dose exploration phase, venetoclax dosing is 400 mg daily (or allometrically-scaled equivalent) for 21 (Dose Level 0) or 14 days (Dose Level -1) using a rolling 6 design. Primary endpoints are determination of the recommended phase 2 dose of venetoclax in combination with CPX-351 and description of toxicities. Secondary endpoints include estimations of CR/CRp/CRi +/- MRD negativity in the context of a phase I study and evaluation of therapy-related cardiac dysfunction. Correlative studies include analysis of venetoclax pharmacokinetics with concomitant CPX-351. At the initial dose level, DLT were encountered and the study is now continuing enrollment at Dose Level -1. Clinical trial information: NCT03826992.
A phase 3, randomized, double-blind, placebo-controlled study of ruxolitinib plus parsaclisib in patients with JAK- and PI3K-inhibitor treatment-naïve myelofibrosis.
Authors: Yacoub Abdulraheem , Erickson-Viitanen Susan , Zhou Feng , Assad Albert 
Published: June 2021

TPS7058 Background: Ruxolitinib (JAK1/JAK2 inhibitor) significantly improves outcomes in patients with myelofibrosis (MF); however, a subset of patients may experience a suboptimal response. Recent phase 2 data showed that addition of PI3Kδ inhibitor parsaclisib to ruxolitinib monotherapy resulted in additional alleviation of MF symptoms and splenomegaly in patients with MF (Yacoub. EHA2020. S216). This phase 3, randomized, double-blind study (INCB 50465-313; NCT04551066), evaluates the combination of ruxolitinib and parsaclisib in patients with MF who are naïve to Janus kinase (JAK) and PI3K inhibitor therapies. Methods: Eligible patients are aged ≥18 years with a diagnosis of primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF, have a Dynamic International Prognostic Scoring System (DIPSS; Passamonti. Blood. 2010;115:1703-1708) risk category of at least Intermediate (INT)-1, palpable spleen ≥5 cm below left subcostal margin; total symptom score ≥10 at screening, ECOG PS 0–2, and life expectancy ≥24 weeks. Patients will be excluded if they previously received therapy with any JAK inhibitor, any PI3K inhibitor, any experimental or standard drug therapy for MF ≤3 months of first study dose and/or lack of recovery from all toxicities related to previous therapies to grade ≤1, have recent history of inadequate bone marrow reserve (eg, platelet count = 50×109/L) or have inadequate liver or renal function at screening. Approximately 440 patients will be randomized (1:1) to ruxolitinib plus parsaclisib 5 mg QD or ruxolitinib plus matching placebo, with stratification at randomization by DIPSS risk category (high vs INT-2 vs INT-1) and platelet count (≥100×109/L vs 50 to = 100×109/L inclusive). Treatment will begin on Day 1, with starting ruxolitinib dose level determined by baseline platelet count, and will continue as long as treatment is tolerated and discontinuation criteria are not met. When the last enrolled patient has completed 24 weeks of treatment, the study will be unblinded and patients randomized to ruxolitinib plus placebo who have adequate hematology parameters will be able to crossover to receive parsaclisib together with continued ruxolitinib. The primary objective is the evaluation and comparison of spleen volume at Week 24 for patients who received ruxolitinib plus parsaclisib versus ruxolitinib plus placebo. Secondary objectives include evaluation and comparison of patient-reported MF symptoms, overall survival, time to onset and duration of response in spleen volume, and safety and tolerability for ruxolitinib plus parsaclisib versus ruxolitinib plus placebo. Sites are opening across the United States, Europe, Asia, and New Zealand. Clinical trial information: NCT04551066.
A phase III clinical trial of adjuvant chemotherapy versus chemoimmunotherapy for stage IB-IIIA completely resected non-small cell lung cancer (NSCLC) patients nadim-adjuvant: New adjuvant trial of chemotherapy versus chemoimmunotherapy.
Authors: Calvo Virginia , Domine Manuel , Sullivan Ivana , Gonzalez-Larriba Jose-Luis , Ortega Ana Laura , Bernabé Reyes , Sala Maria Angeles , Campos Begona , De Castro Javier , Martín-Martorell Paloma , Bosch-Barrera Joaquim , Mielgo Xabier , Vilà Laia , Casal Joaquin , Ros Silver , Martinez Aguillo Maite , Padilla Airam , Sandiego Sergio , Aires Machado Jonathan , Provencio-Pulla Mariano 
Published: June 2021

TPS8581 Background: The results of current studies are considered acceptable evidence to support the hypothesis of efficacy of the proposed combination of immunotherapy with chemotherapy (CT-IO) in patients with NSCLC stages Ib-IIIA candidates for adjuvant treatment. Methods: This is an open-label, randomised, two-arm, phase III, multi-centre clinical trial. Primary objective and endpoint: The primary objective is disease free survival (DFS) defined time from randomization to the earliest event defined as disease recurrence, any new lung cancer (even in the opposite lung), or death from any cause at any known point in time Sample size: 210 patients NSCLC stages Ib-IIIA (Experimental Arm (Adjuvant Chemotherapy-Inmunotherapy + maintenance adjuvant Inmunotherapy): 105 patients, Control Arm (Adjuvant Chemotherapy): 105 patients Treatment Patients randomised to the experimental arm will receive Nivolumab 360mg + Paclitaxel 200mg/m2 + Carboplatin AUC5 for 4 cycles every 21 days (+/- 3 days) as adjuvant treatment followed by maintenance adjuvant treatment for 6 cycles with Nivolumab 480 mg Q4W (+/- 3 days). Patients randomized to the control arm will receive Paclitaxel 200mg/m2 + Carboplatin AUC5 for 4 cycles every 21 days (+/- 3 days) followed by 2 observation visits. Total trial duration: 6.5 years, 3.5 years of recruitment, 1 year of adjuvant treatment or observation and 2 years of follow up. The start date was January 2021. The estimated primary completion date is June 2027. Clinical trial information: NCT04564157.
Blood-based biomarker analysis in high PD-L1 expressing NSCLC treated with PD-1/PD-L1 based therapy with or without the addition of platinum-based chemotherapy.
Authors: Fidler Mary J. , Villaflor Victoria Meucci , Rao Amol , Halmos Balazs , Bertino Erin Marie , Osarogiagbon Raymond U. , Carbone David Paul 
Published: June 2021

TPS9126 Background: Immunotherapy directed against the programmed death-1 / ligand-1 (PD-1/L1) axis has revolutionized the treatment of advanced non-small cell lung cancer (aNSCLC). Tumor PD-L1 is currently the only biomarker validated for predicting patient response to front line PD-1/L1 directed immunotherapy, yet 20% of patients with ≥50% PD-L1 expression die within six months of starting therapy (Reck et al. 2016). Blood-based agents such as autoantibodies and circulating inflammatory biomarkers have stratified patient outcomes on anti-PD-1/L1 immunotherapy in preliminary studies (Tarhoni, Kollipara et al. 2019; Tarhoni, Fidler et al. 2019). Moreover, a serum-based proteomic test that uses mass spectrometry and machine learning to provide three classifications (Good, Intermediate and Poor) has stratified non-treatment naïve aNSLCC patients treated with nivolumab based on their outcomes (Mueller et al. 2020) and identified a subset of patients who progressed rapidly. This study will evaluate these blood-based biomarkers as predictors of response and early progression in patients with >50% PD-L1 positive aNSCLC treated with immunotherapy regimens. Methods: This is a prospective, observational, multicenter study (NCT04676386) designed to assess biomarkers (serum and plasma) as predictive of early progression in 390 patients with aNSCLC treated with anti-PD 1/PD-L1 immunotherapy with or without platinum-based chemotherapy. Key eligibility criteria are treatment naïve aNSCLC with tumor biopsy PD-L1 tumor proportion score > 50%, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2, and ability to consent to participate. Prior to enrollment, tumor specimens will be tested for PD-L1 expression according to participating centers’ standard operating procedures. For each treatment cohort of 195 patients, enrollment will proceed in sub-cohorts to ensure a population with 20% patients with ECOG PS2 and a total of 40 patients with squamous cell carcinoma per treatment arm. Patients will be followed for a maximum of 3 years. Blood draw for biomarker assessment will be performed prior to treatment initiation, start of 3rd cycle and investigator assessed progression. Biomarker analysis will be performed retrospectively. As a secondary objective, this study will evaluate proteomic test performance in predicting early overall survival (OS) and rapid progression, and in stratifying patient survival and response. Exploratory analyses will correlate baseline and serial circulating protein analytes and autoantibodies with the proteomic test, response measures (RECIST 1.1) and toxicities. Enrollment opened in February 2021. Clinical trial information: NCT04676386.