bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I study of AMG 160, a half-life extended bispecific T-cell engager (HLE BiTE immune therapy) targeting prostate-specific membrane antigen, in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Tran Ben , Horvath Lisa , Rettig Matthew , Fizazi Karim , Lolkema Martijn P. , Dorff Tanya B. , Greil Richard , Machiels Jean-Pascal H. , Autio Karen A. , Rottey Sylvie , Adra Nabil , Garje Rohan , Roncolato Felicia , Tagawa Scott T. , Shariat Shahrokh F. , Salvati Mark , Poon Shirley , Kouros-Mehr Hosein 
Published: May 2020

TPS5590 Background: Prostate-specific membrane antigen (PSMA) is a clinically validated therapeutic target for the imaging and treatment of mCRPC. AMG 160 is an HLE BiTE immune therapy designed to redirect T cells to cancer cells by binding to PSMA on cancer cells and CD3 on T cells. BiTE immune therapy leads to direct tumor cell killing, T-cell activation and expansion, and the creation of a pro-inflammatory tumor microenvironment. Combining AMG 160 with a PD-1 inhibitor may enhance antitumor activity by enabling sustained T-cell-dependent killing of tumor cells in the inflamed tumor microenvironment. Methods: NCT03792841 is a phase I study of AMG 160 as monotherapy (part 1) and in combination with pembrolizumab (part 2) in men with histologically/cytologically confirmed mCRPC who are refractory to a novel hormonal therapy (abiraterone, enzalutamide, and/or apalutamide) and have failed 1–2 taxane regimens (or are medically unsuitable or have refused taxanes), who have ongoing castration with total serum testosterone ≤ 50 ng/dL, and have evidence of progressive disease. Patients who received prior PSMA radionuclide therapy may be eligible. Patients with CNS metastases, leptomeningeal disease, spinal cord compression, or active autoimmune disease will be excluded. Primary objectives are to evaluate safety and tolerability and determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of AMG 160 given as monotherapy or in combination with pembrolizumab. Secondary objectives are to characterize pharmacokinetics and preliminary antitumor activity. Exploratory objectives include evaluation of potential pharmacodynamic and patient selection biomarkers, immunogenicity, and patient-reported pain and functional outcomes. The part 1 dose exploration will determine the MTD/RP2D of AMG 160. The part 1 dose expansion will confirm the safety and tolerability of the MTD/RP2D. The part 2 dose exploration will estimate the MTD/RP2D of AMG 160 in combination with pembrolizumab. Evaluation of preliminary antitumor activity will be based on RECIST 1.1 with Prostate Cancer Working Group 3 modifications, PSA response, CTC response, progression-free survival (radiographic and PSA), and overall survival. PSMA PET/CT and FDG PET/CT imaging will be used for evaluation of exploratory objectives. The study opened in February 2019 and is currently recruiting patients into both part 1 and part 2. Clinical trial information: NCT03792841 .
Phase III study of pembrolizumab (pembro) plus enzalutamide (enza) and androgen deprivation therapy (ADT) for patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC): KEYNOTE-991.
Authors: Gratzke Christian , Burgents Joseph E , Niu Cuizhen , Poehlein Christian Heinrich , Drake Charles G. 
Published: May 2020

TPS5595 Background: Pembro, an anti–PD-1 antibody, has shown antitumor activity as monotherapy and in combination with other agents in metastatic castration-resistant prostate cancer (mCRPC). As the antitumor effects of enza may be pro-immunogenic, we hypothesized that combining pembro and enza could show additive or synergistic antitumor activity. Furthermore, pembro + enza previously showed antitumor activity in pts with mCRPC for whom abiraterone failed (KEYNOTE-365, NCT02861573) and in pts with mCRPC for whom enza monotherapy failed (KEYNOTE 199, NCT02787005). These data warrant further evaluation of the combination of pembro + enza when given at the initiation of ADT. Methods: KEYNOTE-991 (NCT04191096) is a phase III trial to evaluate the efficacy and safety of enza + ADT + either pembro or placebo in patients with mHSPC. Approximately 1232 pts will be randomly assigned 1:1 to receive enza 160 mg orally once daily + ADT + pembro 200 mg IV every 3 weeks (Q3W) or enza 160 mg orally once daily + ADT + placebo IV Q3W. ADT is receipt of an LHRH agonist or antagonist during study treatment or bilateral orchiectomy. Treatment will be stratified by prior docetaxel therapy (yes or no) and presence of high-volume disease (yes or no). Pts with mHSPC, with ≥2 bone lesions and/or visceral disease, who are naive to next-generation hormone agents, and who have ECOG PS 0 or 1 are eligible. Pts must provide tissue for biomarker analysis. Responses will be assessed by CT or MRI and radionuclide bone imaging per Prostate Cancer Working Group 3 (PCWG3)–modified RECIST v1.1 by blinded independent central review (BICR) Q12W from the date of randomization. Treatment will continue with pembro for up to 35 cycles, and treatment with enza will proceed continuously from day 1 of cycle 1 until disease progression, unacceptable toxicity, or withdrawal of consent. Dual primary end points are radiographic progression-free survival (PFS) per PCWG3-modified RECIST v1.1 assessed by BICR and overall survival. Secondary end points are time to first subsequent anticancer therapy, time to symptomatic skeletal-related event, PFS2 (progression after next line of therapy or death), prostate-specific antigen (PSA) response rate, time to PSA progression, PSA undetectable rate, objective response rate, duration of response, and time to radiographic soft tissue progression. Other end points are safety and patient-reported outcomes (eg, time to pain progression). Clinical trial information: NCT04191096 .
ADAPTcycle: Adjuvant dynamic marker-adjusted personalized therapy (ADAPT) comparing endocrine therapy plus ribociclib versus chemotherapy in intermediate-risk HR+/HER2- early breast cancer (EBC).
Authors: Harbeck Nadia , Gluz Oleg , Christgen Matthias , Graeser Monika , Hilpert Felix , Krauss Katja , Thill Marc , Warm Mathias , Müller Volkmar , Braun Michael Wilhelm , Just Marianne , Kreipe Hans Heinrich , Nitz Ulrike , Kates Ronald E. , Schinkoethe Timo , Wuerstlein Rachel , Kuemmel Sherko 
Published: May 2020

TPS601 Background: The WSG ADAPT trial program represents the concept of individualization of (neo)-adjuvant decision-making in EBC in a subtype-specific manner. The first WSG ADAPT umbrella trial aimed to establish early predictive molecular surrogate markers for response after a short 3-week induction treatment. The goals of the WSG ADAPT trial program are early response assessment and subtype-specific therapy tailoring to those patients who are most likely to benefit. Methods: WSG-ADAPTcycle is a prospective, multi-center, interventional, two-arm, open-label, (neo)adjuvant, non-blinded, randomized, controlled phase III trial (NCT04055493). It investigates whether patients (pts.) with HR+/HER2- EBC identified during screening as intermediate risk (based on Oncotype DX and response to 3 weeks of preoperative endocrine therapy [ET]) derive additional benefit from 2 years of the CDK4/6 inhibitor ribociclib combined with ET compared to chemotherapy (CT) (followed by standard ET). Co-primary endpoints are disease-free survival (DFS) and distant DFS. It is planned to screen 5600 pts and to randomize 1670 pts in a 3:2 ratio (ribociclib + ET/CT). Study start was in July 2019 (80 sites, enrollment period 36 months) and until date of submission, 180 pts. have been screened and 40 randomized. Pts with HR+/HER2- EBC with clinically enhanced risk (cT2-4 or Ki67 20% or G3 or cN+) are eligible if they fulfill the ADAPT intermediate-risk group criteria: either Recurrence Score (RS) ≤25 and Ki67postendocrine>10%, RS >25 and Ki67postendocrine<10% in p/cN0-1 pts, or RS ≤25 and Ki67postendocrine<10% in c/pN2-3 pts. Treatment duration is 2 years for the ribociclib + ET (premenopausal: AI + GnRH) arm and 16-24 weeks for the CT arm; treatment is possible either in the neoadjuvant (ET + ribociclib duration 16 – 32 weeks) or adjuvant setting. ePROs are collected using CANKADO; ECG monitoring is performed using a novel cardiology-supported CANKADO-based eHealth method. Translational analyses: Exploratory tissue biomarker research will be conducted to assess alterations in molecular markers. In addition, ctDNA/ctRNA from optional blood samples will be assessed for mutations and gene expression. Conclusions: ADAPTcycle seeks to evaluate whether endocrine-based therapy with ET and a CDK 4/6 inhibitor is superior to CT followed by ET in patients with luminal EBC who may be undertreated with ET alone (based on either lack of endocrine responsiveness or high tumor burden). Clinical trial information: 2018-003749-40 .
A phase III trial of nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2- primary breast cancer: CheckMate 7FL.
Authors: Loi Sherene , McArthur Heather L. , Harbeck Nadia , Pusztai Lajos , Delaloge Suzette , Letrent Kristen , Chen Tian , Li Bin , Tatsuoka Kay , Zardavas Dimitrios , Curigliano Giuseppe 
Published: May 2020

TPS604 Background: Patients (pts) diagnosed with primary estrogen receptor-positive (ER+), human epidermal growth factor 2-negative (HER2−) breast cancer (BC) of high grade and/or low ER expression are at increased risk of relapse, despite current standard of care (SoC). Promising data assessing programmed death-1 (PD-1) inhibition coupled with neoadjuvant chemotherapy for pts with high-risk ER+, HER2− BC noted improved pathologic complete response (pCR), which is identified as a valid surrogate endpoint for long-term clinical outcomes. Methods: CheckMate 7FL (NCT04109066) is a randomized, double-blind, placebo-controlled, multicenter, global phase 3 study evaluating nivolumab (NIVO) vs placebo (PBO) in combination with neoadjuvant chemotherapy and adjuvant endocrine therapy (ET) in pts with high-risk, ER+, HER2− primary BC. Eligible pts are male or female, aged ≥18 years with newly diagnosed grade 2 with ER expression of 1–9%, or grade 3, T1c-2, cN1-2 (tumor size ≥2 cm) or T3-T4, cN0-cN2 ER+, HER2− BC. Pts eligible for neoadjuvant chemotherapy and surgery, with adequate organ function, ECOG PS of 0 or 1, and tissue available for biomarker assessments will be enrolled. Approximately 1200 pts will be randomized 1:1 to NIVO or PBO, stratified by programmed death ligand 1 (PD-L1) expression, tumor grade (2 or 3), axillary nodal status (+ or −), and anthracycline + cyclophosphamide schedule (Q3W or Q2W). In the neoadjuvant phase, pts will receive NIVO 360 mg Q3W or PBO + paclitaxel 80 mg/m2 QW for four 3-week cycles, followed by NIVO 360 mg Q3W (or 240 mg Q2W) or matching PBO in combination with either doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 Q3W or Q2W for 4 cycles. Pts will undergo surgery after completion of the neoadjuvant phase. Following surgery, pts will enter the adjuvant phase and receive NIVO 480 mg Q4W or PBO for 7 cycles + investigator’s choice of ET per local SoC. Primary endpoints are pCR (ypT0/is, ypN0) and event-free survival. Secondary endpoints include overall survival, disease-free survival, distant-metastasis-free survival, safety, pCR (ypT0 ypN0 and ypT0/is) rates, overall response rates, residual cancer burden, and quality of life. Interim analyses are planned. The study is currently enrolling. Clinical trial information: NCT04109066 .
Phase Ib/II trial of tisotumab vedotin (TV) ± bevacizumab (BEV), pembrolizumab (PEM), or carboplatin (CBP) in recurrent or metastatic cervical cancer (innovaTV 205/ENGOT-cx8/GOG-3024).
Authors: Vergote Ignace , Concin Nicole , Mirza Mansoor Raza , Andreassen Camilla Mondrup , Lorusso Domenica , Gennigens Christine N. , Banerjee Susana N. , O'Cearbhaill Roisin Eilish , Campos Susana , Viana Nicacio Leonardo , Eaton Lamar , O'Malley David M. , Soumaoro Ibrahima , Monk Bradley J. 
Published: May 2020

TPS6095 Background: Patients (pts) with recurrent/metastatic cervical cancer (r/mCC) receive paclitaxel/platinum or paclitaxel/topotecan ± BEV as first-line standard-of-care therapy. Tissue factor (TF) expression has been associated with poor prognosis in solid tumors, and TF is highly expressed in r/mCC. TV is an investigational antibody-drug conjugate composed of a fully human, TF-directed monoclonal antibody covalently attached to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. Upon internalization, MMAE is released resulting in cell cycle arrest and apoptotic cell death. In pts with previously treated r/mCC, TV monotherapy (IV 2.0 mg/kg Q3W) demonstrated a manageable safety profile and encouraging antitumor activity (investigator-assessed confirmed ORR, 24%; median DOR, 4.2 mo) [Hong DS et al. Clin Cancer Res. 2019. doi: 10.1158/1078-0432.CCR-19-2962]. The preliminary safety and efficacy data for TV monotherapy suggest a positive benefit/risk profile and warrant further investigation of TV in combination with therapies commonly administered to pts with r/mCC. The global, open-label, phase Ib/II trial innovaTV 205/ENGOT-cx8/GOG-3024 (NCT03786081) evaluates the safety and antitumor activity of TV monotherapy and TV in combination with BEV, PEM, or CBP in pts with untreated or previously treated r/mCC. This abstract presents the new TV monotherapy weekly dosing schedule. Results from this study will inform the further clinical development of TV in the treatment of r/mCC. Methods: Approximately 170 adult pts with recurrent or stage IVB squamous, adenosquamous, or adenocarcinoma of the cervix; measurable disease; and ECOG PS 0-1 will be enrolled. The phase I part of the study will consist of 3 dose-escalation arms for identification of the recommended phase II dose (RP2D) of TV administered Q3W with BEV, PEM, or CBP. In this part, previously treated pts will receive escalating doses of TV (IV Q3W) in combination with escalating doses of BEV (IV Q3W), a fixed dose of PEM (IV Q3W), or a fixed dose of CBP (IV Q3W). The phase II part will include 4 expansion arms. In this phase, pts who have not received prior systemic therapy for r/mCC will receive 1) TV RP2D + PEM or 2) TV RP2D + CBP; pts who received 1-2 prior treatments for r/mCC will receive 3) TV RP2D + PEM or 4) TV monotherapy with weekly dosing (IV 3Q4W). The primary endpoint of phase II is ORR by RECIST v1.1. Secondary endpoints include DOR, time to response, PFS, OS, and safety. Clinical trial information: NCT03786081.
SIENDO/ENGOT-EN5: A randomized phase III trial of maintenance with selinexor/placebo after combination chemotherapy in patients with advanced or recurrent endometrial cancer.
Authors: Vergote Ignace , Hamilton Erika Paige , Romero Ignacio , Guerra Eva M. , Buscema Joseph , Laenen Annouschka , Perri Tamar , Estévez-García Purificación , Gomez Raposo Cesar , Levy Tally , Valabrega Giorgio , Martinez Garcia Jeronimo , Mangili Giorgia , Makker Vicky , Michel Dayana , Wang Hongwei , Mirza Mansoor Raza 
Published: May 2020

TPS6105 Background: Endometrial cancer is one of the most common gynecologic malignancies with increasing incidence and mortality. Patients with advanced disease that has relapsed or received prior platinum-based therapy or radiotherapy have limited options and the prognosis remains poor. Selinexor is a novel, oral selective inhibitor of nuclear export (SINE) which forces nuclear retention and activation of tumor suppressor proteins. Selinexor in combination with low dose dexamethasone was recently approved for patients with multiple myeloma. In addition, single agent selinexor has demonstrated broad activity in other hematologic malignancies and solid tumors. In a phase II study, 50 mg/m2 (~80 mg) selinexor administered twice weekly demonstrated a disease control rate of 35% with 2 confirmed partial responses among 23 patients with heavily pretreated endometrial cancer (Vergote I et al. Gynecol Oncol 2020). In the absence of approved maintenance therapies, we conducted this study to evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent endometrial cancer. Methods: This is a multicenter, double-blind, placebo-controlled, randomized phase III study in patients in partial or complete remission after completing at least 12 weeks of taxane-platinum combination therapy for primary Stage IV disease and recurrent disease (i.e., relapse after primary therapy for early stage disease including surgery and/or adjuvant therapy). A total of 192 patients will be enrolled at 80 sites in Europe, North America, and Israel. Patients will be randomized in a 2:1 ratio to either maintenance therapy with 80 mg oral selinexor once weekly or placebo. Stratification factors include primary Stage IV versus first recurrent disease at the time of taxane-platinum therapy and disease status after chemotherapy (partial versus complete response). Treatment will continue until disease progression. The primary endpoint is progression free survival (PFS) per RECIST v1.1. Secondary endpoints include disease-specific survival, overall survival, time to first subsequent therapy, time to second subsequent therapy, PFS on subsequent therapy and safety and tolerability. The study is currently open and enrolling patients. Clinical trial information: NCT03555422.
Head-to-head comparison of the non-G-CSF small molecule single agent (SA) plinabulin with SA pegfilgrastim for the prevention of docetaxel chemotherapy (chemo)-induced neutropenia (CIN) in the protective-1 trial.
Authors: Blayney Douglas W. , Huang Lan , Mohanlal Ramon W. 
Published: May 2020

TPS7087 Background: Plinabulin (Plin) is a small molecule with anti-cancer activity and CIN effects. The Phase (Ph) 2 clinical trial NPI-2358-101 ( NCT00630110 ) evaluated Plin at 20 or 30 mg/m2 on Day (D) 1 and D8) plus D1 Docetaxel (Doc) 75 mg/m2 combination versus D1 Doc alone in patients (pts) with non-small cell lung cancer(NSCLC). In a large ( > 70%) subset of pts with a measurable lung lesion in the lung (per RECIST 1.1) receiving 30 mg/m2 Plin + Doc (n = 38), mOS was 4.6 months longer vs Doc alone (n = 38) (Mohanlal ASCO-SITC 2018). An unexpected post-hoc finding was a CIN benefit with adding at 20 or 30 mg/m2 Plin to Doc: 33% of pts in the Doc arm had grade 4 neutropenia, whereas in the Plin +Doc group 4% of pts (P < 0.0003) (Blayney ASH 2018). Plin boost the number the number of hematopoietic/progenitor cells in bone marrow. We subsequently initiated two global Ph3 programs with Plin: 1. A Ph 3 trial confirming its anticancer activity in NSCLC (study BPI-2358-103; NCT02504489; this trial is ongoing) and 2. An evaluation of Plin for CIN prevention through studies BPI-2358-105 (NCT03102606; PROTECTIVE-1), and study 106 (NCT03294577; PROTECTIVE-2). We previously reported from the Ph 2 portion of study 105, that SA Plin and Pegfigrastim (Peg) had comparable protection against CIN induced by Doc, however in contrast to Peg, Plin did not cause bone pain or thrombocytopenia (Blayney IASLC 2018, ESMO 2018). Plin is given by 30 min IV infusion on the same day of Chemo, 30 min after Chemo. The Ph3 portion of Study 105 in ongoing. Methods: In the Ph 3 portion of PROTECTIVE-1, pts with NSCLC, HRPC or BC are randomized (1:1) to either Plin 40 mg (over 30 minutes on D1; n = 75) or Peg 6mg (on D2, n = 75), and the primary endpoint is Duration of Severe Neutropenia (DSN). Plin 20 mg/m2 is similar to a 40 mg fixed dose. Absolute neutrophil counts (ANC) is determined on D 0, 1,2,3,6,8,9,10, 15 in Cycle 1 The trial aims to demonstrate non-inferiority of Plin vs Peg. Non-inferiority will be declared if the non-inferiority margin (NIM) of 0.65 day will be met, which NIM is more conservative than the 1 day NIM, typically employed for G-CSG biosimilar trials. Pts should have at least 1 risk factor as per NCCN guidelines.The trial is double-blinded to enable reliable PRO, Bone Pain and QoL assessments through validated questionnaires (EQ-5D-5L; EORTC QLQ-C30; Wang Baker Faces Pain Rating Scale). Following an Interim Analysis, the trial will continue without modifications. Clinical trial information: NCT03102606 .
A phase II study of BP1001 (liposomal Grb2 antisense oligonucleotide) in patients with hematologic malignancies.
Authors: Ohanian Maro , Lin Tara L. , Craig Michael , Agrawal Apurv , Halka Kathleen , Tari Ashizawa Ana , Cortes Jorge E. , Roboz Gail J. 
Published: May 2020

TPS7561 Background: The growth factor receptor bound protein-2 (Grb2) is vital to oncogene signaling and tumor progression. BP1001 is a liposome-incorporated Grb2 antisense oligonucleotide that inhibits Grb2 expression. Grb2 inhibition suppresses cancer growth and survival. A Phase I/Ib single center study in patients with refractory/relapsed leukemias demonstrated the safety of BP1001 up to 90 mg/m2 dose and the efficacy of BP1001 in combination with low dose cytarabine (LDAC) in refractory/relapsed acute myeloid leukemia (AML) patients (Ohanian, Lancet Haematol 2018). Based on pharmacokinetic (PK) considerations, the recommended Phase II dose was 60 mg/m2. A phase II study was initiated to explore the clinical impact of BP1001 in combination with LDAC in untreated AML patients. Interim safety and efficacy of BP1001 + LDAC in untreated AML patients was presented at the 2018 Annual ASH Meeting. BP1001 was safely administered to 25 patients with untreated AML, who were considered unfit for standard chemotherapy. Efficacy data compared favorably to what has been reported with available options for unfit patients largely with secondary AML or adverse-risk AML. Since the Interim Data presentation, the study was amended to investigate BP1001 + decitabine combination and include myelodysplastic syndrome (MDS) patients. This is because BP1001 enhanced decitabine anti-leukemic effects in preclinical studies. Methods: This is a multi-center, open-label study with 2 parallel cohorts of BP1001 + decitabine treatment in untreated AML/high risk MDS patients and refractory/relapsed AML/high risk MDS patients who are considered by the investigator unsuitable for or refused intensive chemotherapy. BP1001 is given intravenously (IV) at 60 mg/m2 twice weekly. Decitabine is given 20 mg/m2 IV daily for 5 consecutive days. Each cycle is 28 days. Each cohort can enroll 19 patients, with a decision to stop or proceed to 54 patients. The primary objective of this study is to assess whether BP1001 + decitabine provides higher complete remission rates than decitabine alone (by historical comparison) in AML/high risk MDS patients. The secondary objectives of this study are to assess: Safety of BP1001 + decitabine; partial remissions and blast count reductions; overall survival, time to response and duration of response; minimal residual disease status in patients who achieve complete remission; and plasma PK profile of BP1001. The exploratory objective of this study is to evaluate the association of treatment response with cytogenetic and molecular characteristics. Clinical trial information: NCT02781883 .