Rebeca Melara
Amgen
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Featured researches published by Rebeca Melara.
Pharmaceutical Research | 2011
Yow-Ming C. Wang; Bethlyn Sloey; Teresa Wong; Prerna Khandelwal; Rebeca Melara; Yu-Nien Sun
ABSTRACTPurposeRomiplostim, a treatment for adults with immune thrombocytopenia (ITP), is a novel thrombopoietin mimetic agent with a similar mechanism of action as thrombopoietin with no sequence homology. Structurally, it is a peptibody containing thrombopoietin mimetic peptides and the Fc portion of human IgG1. We investigated romiplostim pharmacokinetics in rodents with a focus on the clearance mechanism.MethodsStudies with appropriate controls were conducted in four models: FcRn knockout mice, thrombocytopenic mice, splenectomized rats, and bilateral nephrectomized rats. Catabolic breakdown of romiplostim was investigated in normal rats. The primary analytical method determines the intact/active romiplostim concentration, and the secondary method determines the sum of romiplostim and its catabolic degradants.ResultsFcRn interaction results in prolonged exposure. Platelets are involved in the target-mediated elimination, a saturable process and more prominent at low dose. Splenectomy does not affect the romiplostim pharmacokinetics in rats, an observation not unexpected. Nephrectomy in rats results in a greater increase of romiplostim exposure at a higher romiplostim dose, a nonlinearity likely due to saturation of competing pathway. Catabolism plays a major role in romiplostim elimination.ConclusionRomiplostim clearance involves multiple mechanisms, including a nonlinear pathway. Consequently, the relative contribution of different mechanisms appears to be dose dependent.
Gynecologic Oncology | 2014
Ignace Vergote; Russell J. Schilder; Charles H. Pippitt; Shirley Wong; Alan N. Gordon; Sidney A. Scudder; Frédéric Kridelka; Luc Dirix; Joseph W. Leach; Sumitra Ananda; Nuwan Nanayakkara; Rebeca Melara; Michael B. Bass; Jason Litten; Henry Adewoye; Robert M. Wenham
OBJECTIVE To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. METHODS In this open-label phase 1b study, patients received trebananib 10 mg/kg or 15 mg/kg IV QW plus PLD 50 mg/m(2) (cohorts A1 and A3, respectively) or topotecan 4 mg/m(2) (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary). RESULTS 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, the most common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n=1) and sudden death (n=1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug-drug interactions were apparent. CONCLUSIONS Trebananib 10mg/kg and 15 mg/kg IV QW plus PLD or topotecan appear to have acceptable toxicity profiles in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. Antitumor activity was evident across all cohorts.
Cancer Chemotherapy and Pharmacology | 2012
Jian-Feng Lu; Erik Rasmussen; Beth Y. Karlan; Ignace Vergote; Lynn Navale; Mita Kuchimanchi; Rebeca Melara; Daniel E. Stepan; David M. Weinreich; Yu-Nien Sun
Cancer Chemotherapy and Pharmacology | 2010
Jian-Feng Lu; Laurent Claret; Liviawati Sutjandra; Mita Kuchimanchi; Rebeca Melara; René Bruno; Yu-Nien Sun
Breast Cancer Research and Treatment | 2012
Richard de Boer; Dusan Kotasek; S. White; Bogda Koczwara; Paul N. Mainwaring; Arlene Chan; Rebeca Melara; Y. Ye; Adeboye H. Adewoye; Robert Sikorski; Peter A. Kaufman
Investigational New Drugs | 2008
Patricia LoRusso; Elisabeth I. Heath; Jesse McGreivy; Yu Nien Sun; Rebeca Melara; Lucy Yan; Lisa Malburg; Megan Ingram; Jeffrey Wiezorek; Li Chen; Mary Jo Pilat
Asia-pacific Journal of Clinical Oncology | 2012
Shirley Wong; Sumitra Ananda; Ignace Vergote; Russell J. Schilder; Charles H. Pippitt; Sidney A. Scudder; Nuwan Nanayakkara; Henry Adewoye; Rebeca Melara; Robert M. Wenham
Journal of Clinical Oncology | 2009
Jian-Feng Lu; Laurent Claret; L. Sutjandra; Mita Kuchimanchi; Daniel E. Stepan; René Bruno; Rebeca Melara; Y. Sun
Journal of Clinical Oncology | 2017
Nick Thatcher; Michael Thomas; Zhiying Pan; Jerome H. Goldschmidt; Michael Schenker; Rebeca Melara; Vladimir Hanes
Cancer Chemotherapy and Pharmacology | 2015
Benjamin Wu; Rebeca Melara; Erik Rasmussen; Lei Zhou; Teresa Wong; Cindy Kitahara; Mark Ma; Jessica Lu; Erick Gamelin; Cheryl A. Pickett; Yu-Nien Sun