Phase Ib study of the MEK inhibitor cobimetinib (GDC-0973) in combination with the PI3K inhibitor pictilisib (GDC-0941) in patients with advanced solid tumors

Summary Purpose We investigated the combination of the MEK inhibitor, cobimetinib, and the pan-PI3K inhibitor, pictilisib, in an open-label, phase Ib study. Experimental Design Patients with advanced solid tumors were enrolled in 3 dose escalation schedules: (1) both agents once-daily for 21-days-on...

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Veröffentlicht in:	Investigational new drugs 2020-04, Vol.38 (2), p.419-432
Hauptverfasser:	Shapiro, Geoffrey I., LoRusso, Patricia, Kwak, Eunice, Pandya, Susan, Rudin, Charles M., Kurkjian, Carla, Cleary, James M., Pilat, Mary Jo, Jones, Suzanne, de Crespigny, Alex, Fredrickson, Jill, Musib, Luna, Yan, Yibing, Wongchenko, Matthew, Hsieh, Hsin-Ju, Gates, Mary R., Chan, Iris T., Bendell, Johanna
Format:	Artikel
Sprache:	eng
Schlagworte:	1-Phosphatidylinositol 3-kinase Adenocarcinoma Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics Appetite loss Azetidines - administration & dosage Azetidines - adverse effects Azetidines - pharmacokinetics Biomarkers Class I Phosphatidylinositol 3-Kinases - antagonists & inhibitors Class I Phosphatidylinositol 3-Kinases - genetics Creatine Creatine kinase Dehydration Design of experiments Diarrhea Endometrial cancer Experimental design Fatigue Female GTP Phosphohydrolases - genetics Humans Hypersensitivity Indazoles - administration & dosage Indazoles - adverse effects Indazoles - pharmacokinetics Inhibitors Kinases Lipase Male MAP kinase Medicine Medicine & Public Health MEK inhibitors Melanoma Membrane Proteins - genetics Metabolic response Middle Aged Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinase Kinases - genetics Nausea Neoplasms - drug therapy Neoplasms - genetics Neoplasms - metabolism Oncology Pharmacology Pharmacology/Toxicology Phase I Studies Phosphoinositide-3 Kinase Inhibitors - administration & dosage Phosphoinositide-3 Kinase Inhibitors - adverse effects Phosphoinositide-3 Kinase Inhibitors - pharmacokinetics Piperidines - administration & dosage Piperidines - adverse effects Piperidines - pharmacokinetics Protein Kinase Inhibitors - administration & dosage Protein Kinase Inhibitors - adverse effects Protein Kinase Inhibitors - pharmacokinetics Proto-Oncogene Proteins p21(ras) - genetics Schedules Solid tumors Stomatitis Studies Sulfonamides - administration & dosage Sulfonamides - adverse effects Sulfonamides - pharmacokinetics Taste disorders Toxicity Treatment Outcome Tumors Vomiting Young Adult
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