Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
CC-486 · 7 trials · 32 indications
A treatment emergent adverse event is any untoward medical occurrence that begins or worsens after the first dose of study treatment, including any unfavorable sign, symptom, disease, or abnormal lab finding, whether or not related to the product, and may include worsening of pre-existing conditions. A Serious Adverse Event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs hospitalization, causes persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect, or is considered an important medical event requiring intervention to prevent these outcomes.
Overall response rate was defined as the combined incidence of Complete Response (CR) or Partial Response (PR), confirmed no less than 4 weeks after the criteria for response were first met, based on independent radiology assessment according to RECIST 1.1 criteria. Complete response was defined as the disappearance of all target lesions and non-target lesions; Partial response is at least a 30% decrease from baseline in the sum of diameters of target lesions with no progression of non-target lesions and no new lesions or disappearance of target lesions with persistence of one or more non-target lesions from baseline.
PFS was defined as the time from the date of start of the study treatment to the date of disease progression or death (any cause) on or prior to the data cut-off date for the statistical analysis, whichever occurred earlier, based on an independent radiology assessment of response using RECIST v1.1 criteria. Progressive disease was defined as at least a 20% increase in the sum of diameters of target or non-target lesions from nadir or appearance of a new lesion.
The observed maximum concentration
The observed time to first maximum concentration
Area under the concentration-time curve from time zero to the last quantifiable time point calculated by the linear trapezoidal rule
Area under the concentration time-curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity. It will be calculated as AUC∞ = \[AUCt + Ct/λz\]. Ct is the last quantifiable concentration
Terminal phase rate constant, determined by linear regression of the terminal points of the log-linear concentration-time curve
Terminal phase half-life, calculated according to the following equation: t½ = 0.693/λz
Apparent total clearance, calculated as Dose/AUC∞
Apparent volume of distribution, calculated according to the equation: Vd/F = (CL/F) / λz
The observed maximum concentration
The observed time to first maximum concentration
Area under the concentration-time curve from time zero to the last quantifiable time point calculated by the linear trapezoidal rule.
Area under the concentration time-curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity. It will be calculated as AUC∞ = \[AUCt + Ct/λz\]. Ct is the last quantifiable concentration.
Terminal phase rate constant, determined by linear regression of the terminal points of the log-linear concentration-time curve
Terminal phase half-life, calculated according to the following equation: t½ = 0.693/λz
Apparent total clearance, calculated as Dose/AUC∞
Apparent volume of distribution, calculated according to the equation: Vd/F = (CL/F) / λz
A DLT included events that started within 28 days of the first dose of CC-486 in a 28-day cycle, constituted a change from baseline irrespective of outcome, as decided by the investigator to be related to CC-486 including: * ≥ Grade (GR) 3 nausea, diarrhea, or vomiting despite the use of medical support * Other significant nonhematologic toxicity of ≥ GR 3 considered not related to the disease or intercurrent illness • Absolute neutrophil count (ANC) \< 0.5 x 10\^9/L for \> 1 week despite growth factor support * Platelets \< 25 x 10\^9/L for \> 1 week despite transfusion support * Failure of recovery to an ANC ≥ 1.0 x 10\^9/L and/or platelets ≥ 50 x 10\^9/L with a hypocellular marrow by 56 days after the start of a cycle of CC-486 not due to relapse or progressive disease. The maximum tolerated dose is defined as the cohort delivering the highest dose in which no more than 33% of the evaluable subjects had a DLT The safety population included subjects who received ≥ 1 dose of CC-486
A TEAE was defined as any AE with an onset date on or after the first dose of IP or any event already present that worsened in severity or increased in frequency after exposure to IP up to 28 days after the last dose. In addition, an AE that occurred beyond the timeframe and was assessed by the doctor as possibly related to IP was considered to be treatment-emergent. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for AEs (NCI CTCAE) version 4.0, where 1= Mild; 2= Moderate; 3= Severe; 4= Life-threatening; 5= Death related to AE. Serious AEs resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in a medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes above.
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity.
| Arm | Type | Description |
|---|---|---|
| CC-486/Oral Azacitidine Administration | EXPERIMENTAL | - |
| Placebo Administration | PLACEBO_COMPARATOR | - |
| Oral Azacitidine (CC-486) | EXPERIMENTAL | This study is an open-label, single-arm study and is divided into the screening period, treatment period and follow-up period. It is intended to evaluate the long-term safety of CC-486 and is to be taken at the same dose, schedule and frequency used from the last dose of CC-486 given in the parent study. |
| CC-486 | EXPERIMENTAL | CC-486 will be administered orally every day on Days 1-14 of a 21 day cycle at a dose of 300 mg. The first 6 participants of Asian-Pacific ethnicity will receive a starting dose of 200 mg. If there are no safety concerns, the 300 mg dose will be administered to all subsequent participants of Asian-Pacific ethnicity. |
| CC-486 in combination with Venetoclax | EXPERIMENTAL | - |
| CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 1 | EXPERIMENTAL | Two 150-mg tablets of CC-486 under fasting condition on PK dosing Day 1, followed by one 300-mg tablet of CC-486 on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered. |
| CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 1 | EXPERIMENTAL | One 300-mg tablet of oral CC-486 under fasting condition on PK dosing Day 1, followed by one 300-mg tablet of oral CC-486 under fed condition on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered. |
| CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 2 | EXPERIMENTAL | One 300-mg tablets of CC-486 under fasting condition on PK dosing Day 1, followed by two 150-mg tablets on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered. |
| CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 2 | EXPERIMENTAL | One 300-mg tablet of oral CC-486 under fed condition on PK dosing Day 1, followed by one tablet of 300-mg oral CC-486 under fasted conditions on PK dosing Day 2; if PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine of Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered. |
| Arm A: CC-486 plus Carboplatin | EXPERIMENTAL | CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability. Carboplatin will be given by intravenous (IV) infusion once every 21 Days at a dosage of AUC x 4. |
| Arm B: CC-486 plus ABI-007 | EXPERIMENTAL | CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability ABI-007 will be administered by intravenous (IV) infusion on two of every three weeks at a dosage of 100 mg/m\^2 |
| Arm C: CC-486 | EXPERIMENTAL | CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability |
| Name | Type | Description |
|---|---|---|
| CC-486 | DRUG | Specified dose on specified days |
| Placebo | OTHER | Specified dose on specified days |
| Venetoclax | DRUG | Specified dose on specified days |
| Vidaza | DRUG | 75mg/m\^2 IV or SC daily x 7 days every 4 weeks for ≤ 6 (four-week) cycles |
| Carboplatin | DRUG | Carboplatin will be given by intravenous (IV) infusion once every 21 Days at a dosage of AUC x 4. |
| ABI-007 | DRUG | ABI-007 will be administered by intravenous (IV) infusion on two of every three weeks at a dosage of 100 mg/m\^2 |
Inclusion Criteria: * Newly diagnosed, histologically confirmed de novo acute myeloid leukemia (AML) or AML secondary to prior myelodysplastic disease or chronic myelomonocytic leukemia (CMML) * Eastern cooperative oncology group performance status of 0, 1, or 2 * Has undergone induction therapy wi...
CC-486 is an investigational oral small molecule being studied for use in oncology, specifically in acute myeloid leukemia, nasopharyngeal neoplasms, hematologic neoplasms, and urinary bladder neoplasms. It is being evaluated as maintenance therapy after allogeneic hematopoietic stem cell transplantation and in combination therapy for acute myeloid leukemia.
CC-486 is an oral formulation of azacitidine, a nucleoside metabolic inhibitor that works by incorporating into DNA and RNA, leading to hypomethylation and direct cytotoxicity. It targets rapidly dividing cells, including cancer cells, by inhibiting DNA methyltransferase, which results in reduced DNA methylation and reactivation of tumor suppressor genes.
CC-486 is being developed by Bristol-Myers Squibb Company, which trades under the ticker symbol BMY on the New York Stock Exchange. The company is conducting clinical trials to evaluate the safety and efficacy of this oral azacitidine formulation across multiple oncology indications.
CC-486 is currently in Phase 2 clinical development. It has completed Phase 1 trials and is being studied in an active Phase 2 trial in China for acute myeloid leukemia. The drug is investigational and has not been approved by regulatory authorities for any indication.
CC-486 has been studied in several clinical trials, including NCT01835587, a completed Phase 1 study as maintenance therapy after allogeneic stem cell transplant in AML or MDS; NCT02494258, a completed Phase 2 long-term safety study in hematological disorders; NCT04887857, a completed Phase 1 combination therapy study in AML; and NCT05413018, an active Phase 2 maintenance therapy study in Chinese AML patients.
Yes, CC-486 is also known as ONUREG, which is the brand name for oral azacitidine. In clinical trials, it is referred to as CC-486 (ONUREG, oral azacitidine), indicating that these names refer to the same drug substance.