bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personalized neoadjuvant strategy in luminal A breast cancer to increase breast conserving surgery (BCS) rate [PLATO study].
Authors: Jung Ji Gwang , Kim Hong Kyu , Kim Yumi , Lee Han-Byoel , Moon Hyeong-Gon , Noh Dong-Young , Han Wonshik 
Published: May 2020

TPS603 Background: The most important and well established benefit of neoadjuvant therapy for breast cancer patients is increased breast conservation rate. However, in ER-positive and HER-2 negative breast cancer, the response to neoadjuvant chemotherapy (NCT) is not as good as other subtype of breast cancer, such as HER-2 or triple-negative breast cancer. In addition, with the advancement of multi-gene assay tools for this subtype, adjuvant chemotherapy is not needed at all in significant proportion of this subtype. Through a selective neoadjuvant therapy, either chemotherapy or endocrine therapy using histopathologic markers and 70-gene assay (Mammaprint. Agendia inc.), we hypothesize that we could increase the breast conservation rate in ER-positive and HER-2 negative breast cancer. Methods: This study is a non-randomized, phase II, prospective study. The main inclusion criteria is women with stage I-IIIA, ER-positive and HER-2 negative breast cancer that tumor size is measurable. BCS is not feasible considering the tumor size, location, and patient's breast size. Two surgeons in each institution will judge the feasibility of BCS. Main exclusion criteria is diffuse malignant microcalcification or multicentric breast cancer. The conversion rate from BCS-ineligible to BCS-eligible with NCT was 35.8% in ER-positive and HER-2 negative breast cancer in our previous study. We assumed that with the study regimen, the rate will be increased to 50.8% (15% increase). Given these estimates, under 10% type II error rate and 90% power, 122 patients in total will be enrolled from nine tertiary hospitals in Korea. All the patients initially will be tested with Mammaprint assay. When the Mammaprint result is high risk, the patients will receive NCT. When the Mammaprint result is low risk, the patients will receive neoadjuvant endocrine therapy. Postmenopausal women receive letrozole 2.5mg per day for 16 weeks. Premenopausal women receive leuprorelin every 4 weeks with letrozole for 16 weeks. Period of neoadjuvant endocrine therapy can be prolonged maximum 24 weeks by physician’s decision. The primary endpoint is conversion rate from BCS-ineligible to BCS-eligible of more than 50%. The secondary endpoint is actual breast conservation rate, pathologic complete response, clinical response rate, and disease-free survival. Clinical trial information: NCT03900637 .
NOGGO Ov-42/MAMOC: Rucaparib maintenance after bevacizumab maintenance following carboplatin-based first line-chemotherapy in ovarian cancer patients.
Authors: Braicu Elena Ioana , Wimberger Pauline , Richter Rolf , Keller Maren , Krabisch Petra , Deryal Mustafa , Runnebaum Ingo B. , Witteler Ralf , Bangemann Nikola , Marmé Frederik , Eichbaum Michael , Heitz Florian , Schmalfeldt Barbara , Egger Eva , Fischer Dorothea , Chekerov Radoslav , Grabowski Jacek P. , Sehouli Jalid 
Published: May 2020

TPS6102 Background: Ovarian cancer (OC) is associated with the highest mortality rates among gynecological malignancies, with most patients being diagnosed in advanced stages. The most common histological subtype is high grade serous OC, which is characterized by deficiency in homologous recombination. Debulking surgery, followed by platinum based chemotherapy and bevacizumab (bev), followed by maintenance therapy with bev, is the standard therapy for advanced BRCA wild type (BRCAwt) OC patients in Germany. BRCA mutant patients will receive maintenance with olaparib, according to SOLO1 data. The anticancer effects of PARP inhibitors (PARPi) seem to be increased by the addition of antiangiogenic drugs. Preclinical data showed increased HRD in tumors pretreated with bev, and clinical trials showed a benefit of the combination of antiangiogenic drugs and PARPi vs. PARPi alone. NOGGO Ov-42/MAMOC trial (NCT04227522) is a phase III, randomized, placebo-controlled study evaluating rucaparib maintenance following bevacizumab maintenance for the treatment of advanced primary high grade BRCAwt OC. Methods: 190 patients with histologically confirmed advanced (FIGO stage IIIA- IV of the 2014 FIGO classification) high grade serous or high grade endometrioid (based on local histopathological findings) OC, fallopian tube cancer, primary peritoneal cancer or clear cell carcinoma of the ovary will be randomized 2:1 to receive either rucaparib 600mg BID or placebo as maintenance therapy following first line chemotherapy with 6 cycles of Carboplatin/Paclitaxel and at least 12 cycles of bev, given together with chemotherapy and as maintenance. Only BRCAwt patients will be included in the trial. Randomization is stratified by surgery planned timepoint (neoadjuvant vs. adjuvant), surgical outcome (no residual tumor mass vs. residual tumor mass), response to chemotherapy followed by bev (CR/NED vs. PR/SD) and study center. Treatment will continue for 24 months or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoint is PFS in BRCAwt patients per RECIST v1.1. Secondary endpoints are PFS2, quality of life (EORTC QLQ-C30/OV28, FSI, SF-12, PROC-CTCAE, every day memory questionnaire), daily activity, time to next medical intervention, time to next subsequent therapy, safety assessments and OS. Clinical trial information: NCT04227522.
ENGOT-EN6/NSGO-RUBY: A phase III, randomized, double-blind, multicenter study of dostarlimab + carboplatin-paclitaxel versus placebo + carboplatin-paclitaxel in recurrent or primary advanced endometrial cancer (EC).
Authors: Mirza Mansoor Raza , Coleman Robert L. , Hanker Lars Christian , Slomovitz Brian M. , Valabrega Giorgio , Im Ellie , Walker Monica , Guo Wei , Powell Matthew A. 
Published: May 2020

TPS6107 Background: Carboplatin-paclitaxel is considered standard systemic anticancer therapy for recurrent or advanced EC for which surgery and/or radiation are not curative. Dostarlimab (TSR-042) is an anti-programmed cell death (PD)-1 humanized monoclonal antibody that has demonstrated antitumor activity and an acceptable safety profile in patients (pts) with recurrent or advanced EC in the GARNET trial. The RUBY trial was designed to evaluate the efficacy and safety of dostarlimab in combination with carboplatin-paclitaxel in recurrent or primary advanced EC compared with carboplatin-paclitaxel alone. Methods: This is a global, randomized, double-blind, multicenter, placebo-controlled study. Eligible pts must have first recurrent or primary stage III or stage IV EC with a low potential for cure by radiation therapy or surgery alone or in combination. Pts with carcinosarcoma are eligible for enrollment. 470 pts will be enrolled from approximately 160 sites in the ENGOT countries, United States, and Canada. Stratification factors are microsatellite instability (MSI) status (MSI-high [MSI-H] or microsatellite stable [MSS]), prior external pelvic radiotherapy (yes or no), and disease status (recurrent, primary stage III, or primary stage IV). Pts will be randomized 1:1 to receive combination dostarlimab 500 mg or placebo + carboplatin AUC 5 + paclitaxel 175 mg/m2 every 3 weeks for 6 cycles followed by dostarlimab 1000 mg or placebo monotherapy every 6 weeks for up to 3 years in the absence of progressive disease, death, unacceptable toxicity, or patient/physician decision to withdraw from the study. The primary endpoint is progression-free survival (PFS) as assessed by the investigator in the all-comers population and the MSI-H population per RECIST version 1.1. Secondary efficacy endpoints are PFS assessed by blinded independent central review per RECIST version 1.1, overall survival, objective response rate, duration of response, disease control rate, safety and tolerability, and patient-reported outcomes. Clinical trial information: NCT03981796.
DUO-E/GOG-3041/ENGOT-EN10: a randomized phase III trial of first-line carboplatin (carb) and paclitaxel (pac) in combination with durvalumab (durva), followed by maintenance durva with or without olaparib (ola), in patients (pts) with newly diagnosed (nd) advanced or recurrent endometrial cancer (EC).
Authors: Westin Shannon Neville , Moore Kathleen N. , Van Nieuwenhuysen Els , Oza Amit M. , Mileshkin Linda R. , Okamoto Aikou , Suzuki Akiko , Meyer Kassondra , Barker Laura , Rhee Joon , Vergote Ignace 
Published: May 2020

TPS6108 Background: There is a high unmet need for advances in EC treatment that provide progression-free survival (PFS) and overall survival (OS) benefits. EC tumors are sensitive to carb/pac (Pectasides et al. Gynecol Oncol 2008). Maintenance therapy with the poly(ADP-ribose) polymerase inhibitor (PARPi) ola (with or without bevacizumab) led to significant PFS benefits in advanced ovarian cancer pts with either nd (SOLO1, Moore et al. NEJM 2018; PAOLA-1, Ray-Coquard et al. NEJM 2019) or recurrent (SOLO2, Pujade-Lauraine et al. Lancet Oncol 2017; Study 19, Friedlander et al. Br J Cancer 2018) platinum-sensitive disease, regardless of BRCA mutation status (PAOLA-1; Study 19), and in BRCA-mutated metastatic pancreatic cancer pts (POLO, Golan et al. NEJM 2019). Molecular features of EC could predict sensitivity to PARPi (de Jonge et al. Clin Cancer Res 2019; Auguste et al. Mod Pathol 2018). PARPi has been shown to prime the immune microenvironment in a preclinical BRCA1 mutant ovarian model (Higuchi et al. Cancer Immunol Res 2015). Clinical trials have demonstrated antitumor activity of the anti-programmed cell death ligand-1 (anti-PD-L1) blocker durva (Antill et al. J Clin Oncol 2019) and anti-programmed cell death-1 (anti-PD-1) antibody therapies (Makker et al. ESMO 2019; Oaknin et al. SGO 2019) in EC pts. The DUO-E trial (EUDRACT 2019-004112-60, D9311C00001, NCT04269200) will investigate whether the addition of durva to carb/pac, followed by durva (with or without ola) maintenance treatment, improves PFS in pts with nd advanced or recurrent EC. Methods: Eligible pts for this multicenter, double-blind, Phase III trial must have nd Stage III/IV or recurrent EC and be naïve to first-line chemotherapy. Pts will be randomized (1:1:1; n=~233 per arm) to: arm A) carb/pac + placebo (pbo) (q3w for six cycles) followed by pbo maintenance treatment; arm B) carb/pac + durva (1120 mg; q3w for six cycles) followed by maintenance treatment with durva (1500 mg q4w) + pbo (tablets bid); or arm C) carb/pac + durva (1120 mg; q3w for six cycles) followed by maintenance treatment with durva (1500 mg q4w) + ola (300 mg bid tablets). Pts received maintenance treatment until disease progression. Primary endpoint: investigator-assessed PFS (RECIST 1.1) of arm B vs. arm A. Key secondary endpoints: PFS of arm C vs. arm A; OS of arm B vs. arm A, and of arm C vs. arm A. Enrollment began in Q1 2020. Clinical trial information: 2019-004112-60.
INDUCE-3: A randomized, double-blind study of GSK3359609 (GSK609), an inducible T-cell co-stimulatory (ICOS) agonist antibody, plus pembrolizumab (PE) versus placebo (PL) plus PE for first-line treatment of PD-L1-positive recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).
Authors: Hansen Aaron Richard , Stanton Thomas S. , Hong Min Hee , Cohen Ezra E.W. , Mehanna Hisham Mohamed , Chisamore Michael Jon , Turner David , Yadavilli Sapna , Bell Kelly , Baccan Carlos , Leone Rosalida , Chen Helen , Zhou Helen , Ellis Catherine Elizabeth , Ballas Marc S. , Hoos Axel , Rischin Danny 
Published: May 2020

TPS6591 Background: Pembrolizumab as part of first-line treatment for patients (pts) with R/M HNSCC has improved survival. However, in order to further improve outcomes in this population investigation of rational combinations targeting different mechanisms that cancers exploit to evade the immune system is required. ICOS, a member of the CD28/B7 immunoglobulin receptor superfamily, provides a co-stimulatory signal augmenting T-cell proliferation, cytokine production, cytotoxic function and survival. GSK609 is a humanized IgG4 antibody selected for its potent agonist activity and non-depleting properties. The rationale for targeting ICOS with GSK609 plus PD-1 blockade with PE is supported by preclinical and clinical evidence (Rischin, et al. Annals of Oncol 2019;30[Supplement_5]:v454–5). INDUCE-3 trial (NCT04128696) will explore if the addition of GSK609 to PE improves outcomes of pts with R/M HNSCC. Methods: INDUCE-3 uses a 2-in-1 adaptive design that has the option to seamlessly expand from an initial Phase 2 to a Phase 3 study. Pts (n = 600) will be stratified by PD-L1 status and HPV status (oropharynx only) then randomly assigned in a 1:1 ratio to receive GSK609 plus PE or PL plus PE, every 3 weeks until progression, unacceptable toxicity, or up to 35 cycles. GSK609 plus PE will be assessed for superiority versus PL plus PE in overall survival (OS) and progression-free survival (PFS) per RECISTv1.1 as dual primary endpoints; secondary endpoints include PFS per immune-based RECIST; milestone OS; safety and tolerability; time to deterioration in patient-reported physical function and pain. Efficacy and patient-reported outcome endpoints will be assessed in the PD-L1 combined positive score (CPS) ≥1 and ≥20 populations. Key eligibility criteria are aged ≥18 years; locally incurable R/M HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx; no prior systemic therapy in the R/M setting; PD-L1 CPS ≥1 by central testing; measurable disease per RECIST v1.1 and ECOG PS 0/1. Recruitment is ongoing in countries across the globe. Funding: Study is funded by GlaxoSmithKline and in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Clinical trial information: NCT04128696 .
Randomized, phase II study of ficlatuzumab with or without cetuximab in patients with pan-refractory, recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Authors: Bauman Julie E. , Roe Denise , Saba Nabil F. , Bauman Jessica Ruth , Kaczmar John M. , Burtness Barbara , Muzaffar Jameel , Julian Ricklie Ann , Wang Steven , Bearelly Shethal , Baker Audrey , Steuer Conor Ernst , Bhatia Aarti K. , Giri Anshu , Caulin Carlos , Stabile Laura P. , Centuori Sara , Chung Christine H. 
Published: May 2020

TPS6594 Background: Patients with pan-refractory R/M HNSCC, with clinical resistance to cytotoxic therapy, anti-EGFR molecular targeting, and immunotherapy, have poor survival. An established tumor-intrinsic resistance mechanism to cetuximab, an anti-EGFR IgG1 monoclonal antibody (mAb), is activation of the hepatocyte growth factor (HGF)/cMet pathway, which converges with the EGFR network at both the PI3K/Akt and MAPK nodes allowing for reciprocal compensation. Moreover, over-expression of HGF in the tumor microenvironment is immunosuppressive. Convergent data suggest that HGF/cMet pathway inhibition concurrent with EGFR blockade may overcome cetuximab resistance. We previously reported a Phase I study of ficlatuzumab, a humanized anti-HGF IgG1 mAb, with cetuximab in cetuximab-resistant R/M HNSCC. The combination showed promising safety, overall response rate (ORR) and progression-free survival (PFS). Preliminary biomarker analyses showed that high circulating cMet was associated with poor PFS whereas serum Veristrat, a proteomic classifier associated with worse prognosis in the setting of anti-EGFR monotherapy, was not. An increase in total peripheral T cells, particularly the CD8+ subset, was associated with treatment response while progression was associated with expansion of a unique myeloid population. We designed a follow-on randomized phase II trial evaluating ficlatuzumab with or without cetuximab in pan-refractory, R/M HNSCC with signaling and immune correlatives. Methods: This is a multicenter phase II trial with a randomized, non-comparative, two-arm design (ficlatuzumab 20 mg/kg with or without cetuximab 500 mg/m2 every 2 weeks) in patients with pan-refractory R/M HNSCC. Key eligibility criteria include: R/M HNSCC; cetuximab resistance (progression during or within 6 months of cetuximab-radiation or palliative cetuximab); platinum resistance; prior exposure to anti-PD1 mAb; ECOG 0-1; consent to baseline research biopsy. The primary objective is to evaluate the efficacy of each arm as measured by PFS. To test the hypothesis that either regimen improves historical PFS from 2 to 3.33 months requires 66 eligible patients. Key secondary endpoints are ORR and survival. Mechanistic biomarkers include tumor HGF/cMet pathway activation, tumor and peripheral immune profiles, soluble cMet, and serum Veristrat. Thirty-five of 66 subjects have enrolled at 6 centers. A Bayesian continuous monitoring rule for futility has not been triggered for either arm. Clinical trial information: NCT03422536 .
ROMAN: Reduction in oral mucositis with avasopasem manganese (GC4419)–Phase III trial in patients receiving chemoradiotherapy for locally advanced, nonmetastatic head and neck cancer.
Authors: Holmlund Jon , Brill Jeffrey Mark , Fairbanks Robert , Saunders Deborah , Sonis Stephen T. , Downs Matt , Anderson Carryn M. 
Published: May 2020

TPS6596 Background: Approximately 70% of patients receiving intensity-modulated radiotherapy (IMRT) plus cisplatin for locally advanced head and neck cancer (HNC) develop SOM, defined as WHO Grade 3 or 4, which limits patients' ability to eat solids (Gr 3) or liquids (Gr 4, requiring enteral nutrition). An RT-induced burst of superoxide initiates oral mucositis (OM) development. GC4419, a superoxide dismutase mimetic, interrupts this process by converting superoxide to H2O2. It showed promising reduction of SOM in a published open-label Phase 1b/2a trial (IJROBP 1 Feb 2018). In a subsequent randomized, double-blind placebo-controlled trial in 223 patients receiving IMRT/cisplatin for HNC (ASCO 2018), 90 mg of GC4419 administered M-F prior to IMRT demonstrated statistically significant reduction in SOM duration (p=0.024, median 1.5 days @ 90 mg vs. 19 days placebo) and meaningful reductions @ 90 mg in SOM incidence (43% vs. 65%) and severity (incidence of Grade 4, 16% vs. 30%). The safety results were acceptable and consistent with the known toxicities of IMRT/cisplatin. Methods: 335 patients at multiple centers in the U.S. and Canada with locally-advanced, nonmetastatic head and neck cancer (oral cavity/oropharyngeal) receiving 70 Gy IMRT (>50 Gy to > 2 oral sites) plus cisplatin (40 mg/m2 qwk x 6-7, or 100 mg/m2 q3wk x 3) are being randomized (double-blinded) 3:2 to 90 mg of GC4419 or placebo, M-F before each RT fraction. Enrollment is stratified by cisplatin schedule and treatment setting (definitive vs. post-op). OM by the WHO scale will be assessed twice weekly during RT & weekly for 2 weeks post RT. The primary efficacy endpoint is incidence of SOM through the end of IMRT. Secondary efficacy endpoints include severity (incidence of Grade 4 OM through the end of IMRT), & days of SOM (days from first to last SOM for all patients, with patients never developing SOM having 0 days of SOM by definition). Days of SOM for the subset developing SOM will be analyzed descriptively. Patients will be followed for one year post IMRT for tumor progression/recurrence and for two years for survival. Clinical trial information: NCT03689712 .
A phase I/II study of IMGN632, a novel CD123-targeting antibody-drug conjugate, in patients with relapsed/refractory acute myeloid leukemia, blastic plasmacytoid dendritic cell neoplasm, and other CD123-positive hematologic malignancies.
Authors: Daver Naval Guastad , Montesinos Pau , DeAngelo Daniel J. , Wang Eunice S. , Todisco Elisabetta , Tarella Corrado , Martinelli Giovanni , Erba Harry Paul , Deconinck Eric , Sweet Kendra L , Walter Roland B. , Levy Moshe Yair , Pemmaraju Naveen , Lane Andrew A. , Rizzieri David , Konopleva Marina , Sloss Callum Mortimer , Wang Jiuzhou , Malcolm Kara E , Zweidler-McKay Patrick A 
Published: May 2020

TPS7563 Background: Overexpression of CD123 occurs in multiple hematological malignancies, including acute myeloid leukemia (AML), blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute lymphoblastic leukemia (ALL) and others, thus making this antigen an attractive target for the development of new therapeutics. IMGN632 is a CD123-targeting antibody-drug conjugate (ADC) comprising a novel anti-CD123 antibody coupled, via a peptide linker, to a unique DNA-alkylating cytotoxic payload of the recently developed IGN (indolinobenzodiazepine pseudodimer) class. Preclinically, IMGN632 has demonstrated potent activity against AML, BPDCN and ALL models, with a wide therapeutic index in animal models, as well as a 150-fold differential cytotoxicity in AML patient samples compared to normal hematopoietic progenitors (PMIDs: 29661755, 30361418). Remarkable sensitivity of BPDCN patient derived xenografts to IMGN632 has been demonstrated (Blood 2018 132:3956). Methods: This Phase I/II study comprises a dose escalation phase designed to establish the recommended phase II dose (RP2D) for IMGN632, as well as dose expansion cohorts to further explore the safety and preliminary anti-leukemia activity of IMGN632. Expansion cohorts were designed to evaluate the following patient populations: adult patients with relapsed or refractory BPDCN or patients with untreated BPDCN who are inappropriate for available therapies, patients with relapsed or refractory AML, or with other CD123+ relapsed or refractory hematologic malignancies including ALL. Inclusion criteria include up to four prior lines of therapy which may include transplant. Patients with active central nervous system disease, history of veno-occlusive disease of the liver, or history of grade IV capillary leak syndrome or non-cardiac grade IV edema are ineligible. Expansion cohorts for unfit frontline and relapsed/refractory BPDCN, and relapsed/refractory ALL continue to enroll at the RP2D (0.045 mg/kg Q3W). Clinical trial information: NCT03386513 .