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Pancreatic Neoplasms: HELP
Articles by Thea Kalebic
Based on 2 articles published since 2010
(Why 2 articles?)

Between 2010 and 2020, Thea Kalebic wrote the following 2 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Clinical Trial A phase II study of antibody-drug conjugate, TAK-264 (MLN0264) in previously treated patients with advanced or metastatic pancreatic adenocarcinoma expressing guanylyl cyclase C. 2017

Almhanna, Khaldoun / Wright, David / Mercade, Teresa Macarulla / Van Laethem, Jean-Luc / Gracian, Antonio Cubillo / Guillen-Ponce, Carmen / Faris, Jason / Lopez, Carolina Muriel / Hubner, Richard A / Bendell, Johanna / Bols, Alain / Feliu, Jaime / Starling, Naureen / Enzinger, Peter / Mahalingham, Devalingham / Messersmith, Wells / Yang, Huyuan / Fasanmade, Adedigbo / Danaee, Hadi / Kalebic, Thea. ·Department of Gastrointestinal Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA. Khaldoun.Almhanna@moffitt.org. · Florida Cancer Specialists, Tampa, FL, USA. · Vall d'Hebron University Hospital, Barcelona, Spain. · Erasme University Hospital, Brussels, Belgium. · HM Universitario Sanchinarro, Centro Integral Oncológico Clara Campal (CIOCC), Madrid, Spain. · Departamento de Ciencias Médicas Clínicas, Universidad San Pablo CEU, Madrid, Spain. · Ramón y Cajal University Hospital, Madrid, Spain. · Massachusetts General Hospital Cancer Center, Boston, MA, USA. · Hospital Universitario Virgen de la Victoria, Málaga, Spain. · The Christie NHS Foundation Trust, Manchester, UK. · Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, USA. · Brugge Oostende Oncologisch Centrum, Bruges, Belgium. · CIBERONC, La Paz University Hospital, Madrid, Spain. · The Royal Marsden NHS Foundation Trust, London, UK. · Dana Farber Cancer Institute, Boston, MA, USA. · University of Texas Health Science Center, San Antonio, TX, USA. · University of Colorado, Aurora, CO, USA. · Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA. ·Invest New Drugs · Pubmed #28527133.

ABSTRACT: Background This phase II open-label, multicenter study evaluated the efficacy, safety, and tolerability of TAK-264 in previously treated patients with advanced or metastatic pancreatic adenocarcinoma expressing guanylyl cyclase C (GCC). Methods Patients with advanced or metastatic pancreatic adenocarcinoma expressing GCC (H-score ≥ 10) received TAK-264 1.8 mg/kg on day 1 of a 21-day cycle as a 30-min intravenous infusion for up to 1 year or until disease progression or unacceptable toxicity. The primary objective was overall response rate (ORR [complete response + partial response (PR)]). Secondary objectives included evaluations of the safety and pharmacokinetic profile of TAK-264 (NCT02202785). Results 43 patients were enrolled and treated with 1.8 mg/kg TAK-264: 11, 15, and 17 patients with low, intermediate, and high GCC expression, respectively. Median number of treatment cycles received was two (range 1-10). The ORR was 3%, including one patient with intermediate GCC expression who achieved a PR. All patients experienced ≥1 adverse events (AE). The majority of patients experienced grade 1/2 AEs affecting the gastrointestinal tract. Fifteen (35%) patients experienced ≥grade 3 drug-related AEs; five (12%) patients had a serious AE. The most common (≥10% of patients) all-grade drug-related AEs were nausea (33%), fatigue (28%), neutropenia (23%), decreased appetite (23%), vomiting (16%), asthenia (16%), and alopecia (14%). Conclusions TAK-264 demonstrated a manageable safety profile; however, the low efficacy of TAK-264 observed in this study did not support further clinical investigation.

2 Article Evaluation of TAK-264, an Antibody-Drug Conjugate in Pancreatic Cancer Cell Lines and Patient-Derived Xenograft Models. 2018

Schreiber, Anna R / Nguyen, Anna / Bagby, Stacey M / Arcaroli, John J / Yacob, Betelehem W / Quackenbush, Kevin / Guy, Joe L / Crowell, Thomas / Stringer, Bradley / Danaee, Hadi / Kalebic, Thea / Messersmith, Wells A / Pitts, Todd M. ·Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, CO, USA. · University of Colorado Cancer Center, Aurora, CO, USA. · Univeristy of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA. · Takeda, Cambridge, MA, USA. ·Clin Cancer Drugs · Pubmed #30631747.

ABSTRACT: Background: Antibody-drug conjugates (ADCs) are an emerging technology consisting of an antibody, linker, and toxic agent, which have the potential to offer a targeted therapeutic approach. A novel target recently explored for the treatment of pancreatic cancer is guanylyl cyclase C (GCC). The objective of this study was to determine the anti-tumorigenic activity of TAK-264, an investigational ADC consisting of an antibody targeting GCC linked to a monomethyl auristatin E payload Methods: The antiproliferative effects of TAK-264 assessed in a panel of eleven pancreatic cancer cell lines. Additionally, ten unique pancreatic ductal adenocarcinoma cancer patient-derived xenograft models were treated with TAK-264 and the efficacy was determined. Baseline levels of GCC were analyzed on PDX models and cell lines. Immunoblotting was performed to evaluate the effects of TAK-264 on downstream effectors. Results: GCC protein expression was analyzed by immunoblotting in both normal and tumor tissue; marked increase in GCC expression was observed in tumor tissue. The Conclusion: TAK-264 has shown suppression activity in pancreatic cancer cell lines and in pancreatic PDX models. These findings support further investigation of ADC targeting GCC.