Trial Outcomes & Findings for Safety and Efficacy of CC-486 in Previously Treated Patients With Locally Advanced or Metastatic Nasopharyngeal Carcinoma (NCT NCT02269943)

Last Updated: 2018-12-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Tumor response was assessed every (Q) 6 weeks for the first 3 evaluations then Q 9 weeks until disease progression as of the cut-off date of 08 August 2017; the median duration of treatment was 257 days for the 200 mg dose and 114.5 days for 300 mg dose

Results posted on

2018-12-12

Participant Flow

This was a multicenter study with 17 sites from the United States, Canada, France. Greece, Italy, Spain, Taiwan, Singapore and Tunisia.

Participants were enrolled according to a Simon 2-stage design. The first 6 participants of Asian-Pacific Island ethnicity received 200 mg/day CC-486 on days 1-14 of each 21-day cycle to monitor safety and tolerability; if there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity would receive the 300 mg daily dose

Participant milestones

Participant milestones
Measure	CC-486 200 mg Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Treatment Period STARTED	6	30
Treatment Period Investigational Product (IP) Stopped	6	30
Treatment Period COMPLETED	0	0
Treatment Period NOT COMPLETED	6	30
Follow-Up Survival Period STARTED	5	26
Follow-Up Survival Period COMPLETED	0	0
Follow-Up Survival Period NOT COMPLETED	5	26

Reasons for withdrawal

Reasons for withdrawal
Measure	CC-486 200 mg Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Treatment Period Death	0	1
Treatment Period Adverse Event	1	10
Treatment Period Progressive Disease	5	17
Treatment Period Symptomatic Deterioration	0	2
Follow-Up Survival Period Death	3	16
Follow-Up Survival Period Lost to Follow-up	0	2
Follow-Up Survival Period Alive	2	8

Baseline Characteristics

The Safety Population included all participants who received at least 1 dose of investigational product (IP)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CC-486 200 mg n=6 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=30 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.	Total n=36 Participants Total of all reporting groups
Age, Continuous	53.2 Years STANDARD_DEVIATION 11.70 • n=5 Participants	52.2 Years STANDARD_DEVIATION 11.60 • n=7 Participants	52.4 Years STANDARD_DEVIATION 11.46 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	25 Participants n=7 Participants	29 Participants n=5 Participants
Race/Ethnicity, Customized Asian	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized White	0 Participants n=5 Participants	23 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic or Latino	6 Participants n=5 Participants	30 Participants n=7 Participants	36 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Fully Active	4 Participants n=5 Participants	11 Participants n=7 Participants	15 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 = Restrictive but ambulatory	2 Participants n=5 Participants	18 Participants n=7 Participants	20 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = Ambulatory but unable to work	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 3 = Limited Self-Care	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Time From Initial Diagnosis to First Dose	3.60 years STANDARD_DEVIATION 3.204 • n=5 Participants	3.86 years STANDARD_DEVIATION 3.358 • n=7 Participants	3.81 years STANDARD_DEVIATION 3.287 • n=5 Participants
Nasopharyngeal Cancer (NPC) Diagnosis Types Undifferentiated Nasopharyngeal Carcinoma	2 Participants n=5 Participants	21 Participants n=7 Participants	23 Participants n=5 Participants
Nasopharyngeal Cancer (NPC) Diagnosis Types Poorly Differentiated Nasopharyngeal Carcinoma	2 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants
Nasopharyngeal Cancer (NPC) Diagnosis Types Other	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Participants with Prior Anti-Cancer Therapies	6 Participants n=5 Participants • The Safety Population included all participants who received at least 1 dose of investigational product (IP)	29 Participants n=7 Participants • The Safety Population included all participants who received at least 1 dose of investigational product (IP)	35 Participants n=5 Participants • The Safety Population included all participants who received at least 1 dose of investigational product (IP)

PRIMARY outcome

Timeframe: Tumor response was assessed every (Q) 6 weeks for the first 3 evaluations then Q 9 weeks until disease progression as of the cut-off date of 08 August 2017; the median duration of treatment was 257 days for the 200 mg dose and 114.5 days for 300 mg dose

Population: The Efficacy Evaluable Population included all enrolled participants who met eligibility criteria and either received 2 cycles of CC-486 at any dose and discontinued treatment for progressive disease or received 4 cycles of CC-486 and had a baseline and at least 2 post-screening tumor assessments.

Outcome measures

Outcome measures
Measure	CC-486 200 mg n=5 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=20 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Percentage of Participants Who Achieved a Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Based on an Independent Radiology Assessment (IRA)	0 percentage of participants Confidence interval could not be calculated because there were no participants who had a response.	15.0 percentage of participants Interval 4.2 to 34.4

PRIMARY outcome

Timeframe: From Day 1 of documented disease progression; up to data cut off date of 08 August 2017; median follow-up time for censored participants was 12.3 months

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.

Outcome measures

Outcome measures
Measure	CC-486 200 mg n=5 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=20 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Kaplan Meier Estimate of Progression-Free Survival (PFS) Based on an Independent Radiology Assessment According to RECIST 1.1 Criteria	6.2 months Interval 1.4 to NA = Upper limit of the confidence interval (CI) for PFS could not be calculated because the upper limit was not reached due to limited number of events.	4.4 months Interval 1.6 to 7.3

SECONDARY outcome

Timeframe: From Day 1 of study treatment to the first date of progressive disease or death; up to data cut-off date of 08 August 2017; overall median follow-up time for censored participants was 20.4 months

Overall survival was the time from the first dose of study drug to patient death from any cause. Participants who did not die were censored at the last known time the patient was alive date or the clinical data cutoff date, whichever was earlier.

Outcome measures

Outcome measures
Measure	CC-486 200 mg n=5 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=20 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Kaplan Meier Estimate of Overall Survival	18.0 months Interval 15.9 to NA = the CI for overall survival could not be calculated because the upper limit was not reached due to limited number of events.	NA months Interval 12.5 to NA = The median and upper limit of the CI for overall survival could not be calculated because the median or upper limit was not reached due to limited number of events.

SECONDARY outcome

Timeframe: Tumor response was assessed every 6 weeks for the first 3 evaluations then every 9 weeks until disease progression. As of the cut-off date of 08 August 2017 the median duration of treatment was 257 days for the 200 mg dose and 114.5 days for 300 mg dose

Population: Efficacy Evaluable Population = enrolled participants who met eligibility criteria and either received 2 cycles of IP at any dose and discontinued treatment for progressive disease or received 4 cycles of IP and had at least 2 post-screening tumor exams.

Disease Control Rate (DCR) was defined as the percentage of participants with a CR, PR, confirmed ≥ 4 weeks after the criteria for response were first met, or stable disease for ≥ 16 weeks from the first treatment, based on independent radiology assessment using RECIST 1.1 criteria. A complete response was defined as the disappearance of all target lesions and non-target lesions; a 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. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease

Outcome measures

Outcome measures
Measure	CC-486 200 mg n=5 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=20 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Percentage of Participants With Stable Disease for ≥ 16 Weeks From the Date of the First Treatment, or CR or PR According to RECIST 1.1 Criteria and Based on an Independent Radiology Assessment	60.0 percentage of participants Interval 18.9 to 92.4	50.0 percentage of participants Interval 30.2 to 69.8

SECONDARY outcome

Timeframe: From date of first dose of study treatment to 28 days after last dose of study treatment; up to final data cut-off date of 08 August 2017; median treatment duration was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg

Population: The Safety Population included all participants who received at least 1 dose of IP.

Treatment-emergent adverse events (TEAEs) were defined as any adverse event (AE) or serious adverse event (SAE) that occurred or worsened on or after the day of the first dose of the investigational product (IP) through 28 days after the last dose of IP. In addition, any SAE with an onset date more than 28 day after the last dose of IP that was assessed by the investigator as related to IP was considered a TEAE. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and based on the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death.

Outcome measures

Outcome measures
Measure	CC-486 200 mg n=6 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=30 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Number of Participants With Treatment Emergent Adverse Events Any TEAE	6 Participants	30 Participants
Number of Participants With Treatment Emergent Adverse Events Any TEAE Related to IP	6 Participants	28 Participants
Number of Participants With Treatment Emergent Adverse Events Any Serious TEAE	4 Participants	12 Participants
Number of Participants With Treatment Emergent Adverse Events Any Serious TEAE Related to IP	3 Participants	7 Participants
Number of Participants With Treatment Emergent Adverse Events Any CTCAE Grade 3 or 4 TEAE	6 Participants	20 Participants
Number of Participants With Treatment Emergent Adverse Events Any CTCAE Grade 3 or 4 TEAE Related to IP	6 Participants	16 Participants
Number of Participants With Treatment Emergent Adverse Events Any TEAE Leading to Death	1 Participants	1 Participants
Number of Participants With Treatment Emergent Adverse Events Any TEAE Leading to Dose Reduction	5 Participants	9 Participants
Number of Participants With Treatment Emergent Adverse Events Any TEAE Leading to Drug Interruption	4 Participants	9 Participants
Number of Participants With Treatment Emergent Adverse Events Any TEAE Leading to IP Discontinuation	1 Participants	10 Participants

SECONDARY outcome

Timeframe: Blood samples for oral azacitidine PK assessment were collected prior to each dose (pre-dose) and over the 8-hour period following each dose (0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose or similar schedule).

Population: The PK population includes participants with evaluable CC-486 plasma PK profiles.

Area under the plasma concentration-time curve from Time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.

Outcome measures

Outcome measures
Measure	CC-486 200 mg n=6 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=7 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of CC-486 (AUC-t) Cycle 1 Day 1	390.0 ng*h/mL Geometric Coefficient of Variation 58.8	351.7 ng*h/mL Geometric Coefficient of Variation 87.5
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of CC-486 (AUC-t) Cycle 1 Day 14	130.3 ng*h/mL Geometric Coefficient of Variation 995.5	461.3 ng*h/mL Geometric Coefficient of Variation 104.2

SECONDARY outcome

Population: The PK population includes participants with evaluable CC-486 plasma PK profiles.

Area under the plasma concentration-time curve from Time 0 extrapolated to infinity, calculated as \[AUCt + Ct/ λz\]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC %Extrap was ≥25%, AUC inf was not reported.

Outcome measures

Outcome measures
Measure	CC-486 200 mg n=6 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=7 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Area Under the Plasma Concentration -Time Curve From 0 Extrapolated to Infinity (AUC-inf, AUC0-∞) Of CC-486 Cycle 1 Day 1	392.5 ng*h/mL Geometric Coefficient of Variation 58.3	354.9 ng*h/mL Geometric Coefficient of Variation 87.1
Area Under the Plasma Concentration -Time Curve From 0 Extrapolated to Infinity (AUC-inf, AUC0-∞) Of CC-486 Cycle 1 Day 14	138.0 ng*h/mL Geometric Coefficient of Variation 802.1	466.0 ng*h/mL Geometric Coefficient of Variation 104.7

SECONDARY outcome

Population: The PK population includes participants with evaluable CC-486 plasma PK profiles

Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

Outcome measures

Outcome measures
Measure	CC-486 200 mg n=6 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=7 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Maximum Observed Concentration (Cmax) Of CC-486 Cycle 1 Day 1	266.3 ng/mL Geometric Coefficient of Variation 53.8	170.7 ng/mL Geometric Coefficient of Variation 95.0
Maximum Observed Concentration (Cmax) Of CC-486 Cycle 1 Day 14	102.7 ng/mL Geometric Coefficient of Variation 412.0	287.0 ng/mL Geometric Coefficient of Variation 50.7

SECONDARY outcome

Population: The PK population includes participants with evaluable CC-486 plasma PK profiles.

Time to Cmax, obtained directly from the observed concentration versus time data.

Outcome measures

Outcome measures
Measure	CC-486 200 mg n=6 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=7 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Time to Reach Maximum Concentration (Tmax) Of CC-486 Cycle 1 Day 1	1.0 Hours Interval 0.5 to 1.5	1.3 Hours Interval 0.5 to 1.5
Time to Reach Maximum Concentration (Tmax) Of CC-486 Cycle 1 Day 14	1.0 Hours Interval 0.0 to 2.0	1.0 Hours Interval 0.5 to 3.0

SECONDARY outcome

Population: The PK population includes participants with evaluable CC-486 plasma PK profiles.

Terminal phase half-life in plasma, calculated as \[(ln 2)/λz\]. t1/2 was only calculated when a reliable estimate for λz could be obtained.

Outcome measures

Outcome measures
Measure	CC-486 200 mg n=6 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=7 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Terminal Half-Life (t1/2) of CC-486 Cycle 1 Day 1	0.562 Hours Geometric Coefficient of Variation 23.1	0.635 Hours Geometric Coefficient of Variation 24.2
Terminal Half-Life (t1/2) of CC-486 Cycle 1 Day 14	0.584 Hours Geometric Coefficient of Variation 17.2	0.640 Hours Geometric Coefficient of Variation 32.0

SECONDARY outcome

Population: The PK population includes participants with evaluable CC-486 plasma PK profiles.

Apparent volume of distribution, calculated as \[(CL/F)/λz\].

Outcome measures

Outcome measures
Measure	CC-486 200 mg n=6 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=7 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Apparent Total Clearance (CL/F) Of CC-486 Cycle 1 Day 1	509.5 Liters/hour Geometric Coefficient of Variation 58.3	845.3 Liters/hour Geometric Coefficient of Variation 87.1
Apparent Total Clearance (CL/F) Of CC-486 Cycle 1 Day 14	1450 Liters/hour Geometric Coefficient of Variation 802.1	643.7 Liters/hour Geometric Coefficient of Variation 104.7

SECONDARY outcome

Population: The PK population includes participants with evaluable CC-486 plasma PK profiles.

Apparent volume of distribution, calculated as \[(CL/F)/λz\].

Outcome measures

Outcome measures
Measure	CC-486 200 mg n=6 Participants Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=7 Participants Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Apparent Volume of Distribution (Vz/F) Of CC-486 Cycle 1 Day 1	412.9 Liters Geometric Coefficient of Variation 42.9	774.6 Liters Geometric Coefficient of Variation 78.6
Apparent Volume of Distribution (Vz/F) Of CC-486 Cycle 1 Day 14	1221 Liters Geometric Coefficient of Variation 581.3	594.8 Liters Geometric Coefficient of Variation 69.7

Adverse Events

CC-486 200 mg

Serious events: 4 serious events

Other events: 6 other events

Deaths: 4 deaths

CC-486 300 mg

Serious events: 12 serious events

Other events: 29 other events

Deaths: 18 deaths

Serious adverse events

Other adverse events

Additional Information

Anne McClain, Senior Manager, Clinical Trial Disclosure

Celgene Corporation

Phone: 888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year from study completion. Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission or defer publication to permit patent applications.
Publication restrictions are in place

Restriction type: OTHER

Measure	CC-486 200 mg n=6 participants at risk Asian-Pacific island participants received CC-486 200 mg tablets by mouth (PO) on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event, a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death. If well tolerated, and there were no safety concerns, subsequent participants of Asian-Pacific Island ethnicity were administered CC-486 300-mg PO daily for 14 days of a 21-day cycle.	CC-486 300 mg n=30 participants at risk Participants received CC-486 300 mg tablets by mouth on days 1-14 of each 21-day cycle until radiologic disease progression, unacceptable toxicity, adverse event (AE), a new anticancer therapy is begun, withdrawal of consent, subject refusal, physician decision, or death.
Blood and lymphatic system disorders Febrile neutropenia	33.3% 2/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	6.7% 2/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Blood and lymphatic system disorders Neutropenia	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Congenital, familial and genetic disorders Tracheo-oesophageal fistula	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Eye disorders Cataract	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Gastrointestinal disorders Dysphagia	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	6.7% 2/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Gastrointestinal disorders Nausea	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Gastrointestinal disorders Vomiting	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	6.7% 2/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
General disorders Asthenia	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
General disorders Fatigue	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
General disorders Pyrexia	16.7% 1/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Infections and infestations Pneumonia	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Infections and infestations Septic shock	16.7% 1/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	0.00% 0/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Investigations Neutrophil count decreased	33.3% 2/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	0.00% 0/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Nervous system disorders Brain oedema	16.7% 1/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	0.00% 0/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Nervous system disorders Cerebrovascular accident	16.7% 1/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Nervous system disorders Hypoaesthesia	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/6 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.	3.3% 1/30 • From Day 1 of study treatment until 28 days after the last dose of IP and those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP; up to final cut-off date of 08 August 2017; median duration of study treatment was 257 days for CC-486 200 mg and 114.5 days for CC-486 300 mg.