Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
CC-223 · 3 trials · 9 indications
AUC-area under the plasma concentration-time curve;
Total \[14C\]-radioactivity in whole blood, plasma, urine and feces
Cumulative excretion of Total \[14C\]-radioactivity (as fraction of radioactive dose) in urine and feces
Total \[14C\]-radioactivity whole blood-to-plasma ratios
Concentration of CC-223 and M1 metabolite (O-desmethyl-CC-223) in plasma, urine, and feces samples collected up to 14 times from the day prior to dosing to 8 days after dosing.
Cmax: Maximum observed concentration in plasma
Tmax: Time to maximum concentration
AUC: Area under the plasma concentration-time curve
t1/2: Terminal half-life
A dose-limiting toxicity was defined as: - ≥ Grade 3 (per Common Terminology Criteria for Adverse Events \[CTCAE\] Version 4) clinically relevant adverse event (AE) or laboratory abnormality suspected to be related to CC-223 that commenced within 30 days of first dose, except alopecia, Grade 3 rash of the acneiform or maculopapular type for \< 5 days, Grade 3 diarrhea or vomiting lasting \< 72 hours, repeated occurrence of Grade 3 hyperuricaemia in subjects with Grade 3 hyperuricemia at baseline, hyperglycemia, hematologic and liver function test (LFT) abnormalities due to disease progression. - Grade 2 fasting hyperglycemia lasting \> 14 days or ≥ Grade 3 lasting \> 4 days despite optimal medical treatment. - Hematological toxicities including febrile neutropenia, Grade 4 neutropenia or thrombocytopenia for \> 7 days, or Grade 3/4 thrombocytopenia with clinically significant bleeding. - Grade 4 LTFs - AE suspected to be CC-223 related necessitating dose reduction during cycle 1.
Cmax is defined as the maximum observed concentration (in plasma), obtained directly from the observed concentration versus time data. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Tmax is defined as the time to Cmax, obtained directly from the observed concentration versus time data. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
AUC0-24 is defined as the area under the concentration-time curve from Time 0 to 24 hours after a dose. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
AUCinf is defined as the area under the concentration-time curve from Time 0 extrapolated to infinity. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL. AUCinf was not assessed following multiple dosing as the blood sampling schedule on Day 15 did not allow robust assessment of the terminal elimination rate constant.
Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL. T1/2 was not assessed following multiple dosing as the blood sampling schedule on Day 15 did not allow robust assessment of the terminal elimination rate constant.
CL/F is defined as the apparent total body clearance when dosed orally, calculated as Dose/AUCinf. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL. VZ/F was not assessed following multiple dosing as the blood sampling schedule on Day 15 did not allow robust assessment of the terminal elimination rate constant.
Progression free survival rate of GBM participants at 6 months is defined as the percentage of participants without progressive disease per Evaluation Criteria in Solid Tumors (RECIST) 1.1 6 months after starting study treatment. Progressive disease is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
| Arm | Type | Description |
|---|---|---|
| CC-223 | EXPERIMENTAL | CC-223 administration on study day 1 of Period 1 and study day 5 of Period 2 |
| Ketokonazole | ACTIVE_COMPARATOR | Ketoconazole administration on study days 1 through 8 of Period 2 |
| 20 mg oral CC-223 with microtracer | EXPERIMENTAL | A single 20-mg oral dose of CC-223 capsule containing a microtracer of \[14C\]-CC-223 solution |
| 20 mg oral CC-223 fasting | EXPERIMENTAL | A single 20-mg oral dose of CC-223 tablet under fasting conditions |
| 20 mg oral CC-223 fed | EXPERIMENTAL | A single 20-mg oral dose of CC-223 tablet under fed conditions |
| Name | Type | Description |
|---|---|---|
| CC-223 | DRUG | CC-223 20 mg tablets |
| Ketoconazole | DRUG | Ketoconazole 400 mg tablets |
Inclusion Criteria: 1. Must understand and voluntarily sign a written informed consent form before participation. 2. Must be able to communicate with the study doctor, understand and comply with the requirements of the study, and agree to adhere to restrictions and examination schedules. 3. Healthy...
CC-223 is an investigational small molecule being studied for multiple myeloma, non-small cell lung cancer, and other advanced solid tumors. It has also been evaluated in healthy volunteers for safety and pharmacokinetic studies. All clinical trials of CC-223 are in Phase 1 and have been completed.
CC-223 is a small molecule being developed by Bristol-Myers Squibb. Its molecular target has not been disclosed in available clinical trial information. The drug has been studied in Phase 1 trials for multiple myeloma, non-small cell lung cancer, and other advanced cancers.
CC-223 is being developed by Bristol-Myers Squibb Company, which trades under the ticker BMY. The drug is an investigational small molecule that has completed Phase 1 clinical trials for multiple myeloma, non-small cell lung cancer, and other advanced solid tumors.
CC-223 is in Phase 1 clinical development. All four clinical trials of CC-223 are Phase 1 studies and have been completed. The drug is investigational and has not been approved by regulatory authorities for any indication.
CC-223 has been studied in four completed Phase 1 trials. NCT01177397 assessed safety and efficacy in advanced solid tumors, non-Hodgkin lymphoma, or multiple myeloma. NCT01545947 studied CC-223 with erlotinib or oral azacitidine in non-small cell lung cancer. NCT01611467 and NCT01896323 evaluated metabolism and drug interactions in healthy volunteers.
CC-223 is also known by the code name CC-223. No other alternative names have been disclosed in clinical trial records. The drug is an investigational small molecule being developed by Bristol-Myers Squibb for multiple myeloma and other cancers.