Lymphoma, Non-Hodgkin
Conditions
Keywords
CC-122, Phase1, solid tumor, non-Hodgkin's lymphom
Brief summary
To determine the safety and tolerability of CC-122 when administered orally to adult Japanese subjects with advanced solid tumors or Non-Hodgkin's Lymphoma (NHL) and to define the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
Detailed description
This is a phase 1, multicenter, open-label, dose-escalation study that will evaluate the safety, tolerability, (Pharmacokinetics) PK, and preliminary efficacy of CC-122 in Japanese subjects with advanced solid tumors or Non-Hodgkin's Lymphoma (NHL). Subjects will receive ascending dose levels of CC-122 from Cycle 1 onwards to measure PK and to determine safety and tolerability. An initial cohort of at least three subjects will be given CC-122 at a dose of 2.0 mg on an intermittent dosing schedule (5 continuous days out of 7 days per week) and 3-6 subjects will be enrolled in subsequent dose levels. Dose escalation for subsequent cohorts will proceed according to a standard dose escalation design (3+3 design) (Storer, 1989) to establish initial toxicity.
Interventions
DRUGCC-122
5 continuous days out of 7 days per week intermittent dosing
Sponsors
Celgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures are conducted 2. 20 years or older, with histological or cytological confirmation of advanced solid tumors or Non-Hodgkin's Lymphoma (NHL), including those who have progressed on standard anticancer therapy or for whom no other conventional therapy exists 3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 for all tumors 4. Subjects must have the following laboratory values: ・Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L * Hemoglobin (Hgb) ≥ 9 g/dL, drawn at least 7 days after the last RBC transfusion * Platelets (Plt) ≥ 100 x 109/L, drawn at least 7 days after the last platelet transfusion * Potassium within normal limits or correctable with supplements * Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) or ≤ 5.0 x ULN if liver tumors are present * Serum bilirubin ≤ 1.5 x ULN; subjects with serum bilirubin \>1.5 x ULN and ≤ 2 x ULN may be enrolled if agreed to by the sponsor * Serum creatinine ≤ ULN or 24-hour clearance ≥ 50 mL/min * Negative serum pregnancy test in females of childbearing potential as per the CC-122 Pregnancy Prevention Rist Management Plan 5. Able to adhere to the study visit schedule and other protocol requirements 6. Must adhere to the Pregnancy Prevention Rist Management Plan
Exclusion criteria
1. Subjects with primary central nervous system (CNS) malignancies or symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed 2. Known acute or chronic pancreatitis 3. Any peripheral neuropathy ≥ NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade 2 4. Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management 5. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: * Left Ventricular Ejection Fraction (LVEF) \< 45% as determined by Multiple Gated Acquisition Scan (MUGA) scan or Echocardiogram (ECHO) * Complete left bundle branch, or bifascicular block * Congenital long QT syndrome * Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation * QTcF \> 460 msec on screening electrocardiogram (ECG) (mean of triplicate recordings) * Unstable angina pectoris or myocardial infarction ≤ 3 months prior to starting CC-122 * Troponin-T value \>0.4 ng/mL or Brain Natriuretic Peptide (BNP) \>300 pg/mL Subjects with baseline troponin-T \>ULN or BNP \>100 pg/mL are eligible but must and optimization of cardioprotective therapy. * Other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure ≥ 160/95 mmHg) 6. Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks, whichever is shorter, prior to starting CC-122 or who have not recovered from side effects of such therapy. Luteinizing hormone-releasing hormone (LHRH) agonists will be allowed for subjects with metastatic prostate cancer 7. Major surgery ≤ 2 weeks prior to starting CC-122 or still recovering from post operative side effects 8. Women who are pregnant or breast feeding. Adults of reproductive potential not employing two forms of birth control as per Pregnancy Prevention Risk Management Plan (PPRMP) 9. Known human immunodeficiency virus (HIV) infection 10. Known acute or chronic hepatitis B or C virus infection 11. Status post solid organ transplant 12. Less than 100 days for subjects receiving autologous hematologic stem cell transplant (HSCT); or 6 months for subjects receiving allogeneic HSCT, or if otherwise not fully recovered from HSCT-related toxicity a. The 6-month exclusionary period for recovery from HSCT-associated toxicity, applies regardless of whether an autologous or allogeneic transplant was performed 13. Known hypersensitivity to any component of the formulation of CC-122 14. Any significant medical condition (including active or controlled infection or renal disease), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study 15. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study 16. Any condition that confounds the ability to interpret data from the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Accumulation Index of CC-122 | 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) | Accumulation Index defined as AUCtau (Cycle 1 Day 10, 11 or 12)/AUCtau (Cycle 1 Day 1) |
| Pharmacokinetic Parameters of CC-122: CL/F | 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) | Apparent clearance (CL/F) |
| Pharmacokinetic Parameters of CC-122: Vz/F | 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) | Apparent volume of distribution (Vz/F) |
| Number of Participants With Dose-Limiting Toxicities (DLTs) | From first dose up to at least 28 days (Cycle 1) | NCI CTCAE Version 4.03 will be used to grade adverse events. Events described below will be classified as DLTs: * Non-hematologic AEs: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3 * Laboratory abnormalities: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3 * Hematologic: Any febrile neutropenia, Grade 4 neutropenia lasting \> 7 days, Grade 4 thrombocytopenia lasting \> 24 hours or thrombocytopenia of any grade requiring platelet transfusions, Any Grade 3/4 thrombocytopenia with clinically significant bleeding * Hepatic: Grade 4 liver function tests or Grade 3 ALT with Grade 2 or higher bilirubin will be considered a DLT, irrespective of underlying attribution. Other Grade 3 LFTs due to disease progression in the liver will not be considered DLTs * Other adverse events: Suspected to be related to CC-122 and necessitating a dose reduction during the DLT evaluation period |
| Maximum Tolerated Dose (MTD) | From first dose up to at least 28 days (Cycle 1) | The MTD is defined as the last dose level below the non-tolerated dose (NTD) with zero or one out of six evaluable participants experiencing dose-limiting toxicities (DLTs) during the DLT evaluation period. At least 6 participants will be enrolled at the MTD/recommended phase 2 dose (RP2D). MTD will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria Version 4.03 |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From first dose to 28 days post last dose of investigational product (Up to approximately 92 months) | An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria version 4.03 |
| Pharmacokinetic Parameters of CC-122: AUC0-t | 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) | Area under the plasma concentration time-curve up to the last measurable concentration (AUC0-t) |
| Pharmacokinetic Parameters of CC-122: AUCtau | 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) | Area under the plasma concentration time-curve during a dosing interval (AUCtau) |
| Pharmacokinetic Parameters of CC-122: Cmax | 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) | Peak (maximum) plasma concentration (Cmax) |
| Pharmacokinetic Parameters of CC-122: Tmax | 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) | Time to maximum plasma concentration (Tmax) |
| Pharmacokinetic Parameters of CC-122: t1/2 | 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) | Terminal half-life of CC-122 (t1/2) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) | From first dose until objectively documented progression (Up to 92 Months) at Day 15 of Cycle 2, 4, 6, and every 3 cycles thereafter (Cycle = 28 Days) | DoR for NHL patients is defined as the time from the date when complete response (CR) or partial response (PR), whichever is first recorded are met, until the date when disease progression (PD) is first objectively documented, or the date of the last adequate tumor assessment when no disease progression is documented throughout the study according to International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR=disappearance of all evidence of disease. PR=regression of measurable disease and no new sites. Progressive disease (PD)=any new lesion or increase by \>=50% of previously sites from nadir. |
| Best Overall Response (BOR) | From first dose until objectively documented progression (Up to 92 Months) at Day 15 of Cycle 2, 4, 6, and every 3 cycles thereafter (Cycle = 28 Days) | BOR by investigator is defined according to International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma for NHL patients and Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for solid tumors patients. For NHL, complete remission (CR)=disappearance of all evidence of disease. Partial response (PR)=regression of measurable disease and no new sites. Stable disease (SD)=failure to attain CR/PR or PD. Progressive disease (PD)=any new lesion or increase by \>=50% of previously sites from nadir. For solid tumors, complete response (CR)=disappearance of all target and non-target lesions and no new lesions. PR=at least a 30% decrease in the sum of diameters of target lesions and no new lesions. SD=neither sufficient shrinkage to qualify for PR or increase to qualify for PD. PD=at least 20% increase in the sum of diameters of target lesions from nadir. |
Countries
Japan
Participant flow
Pre-assignment details
15 participants treated
Participants by arm
| Arm | Count |
|---|---|
| AIC 2.0 mg CC-122 administered orally at a dose of 2.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using active ingredient in capsule (AIC) | 3 |
| AIC 3.0 mg CC-122 administered orally at a dose of 3.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using active ingredient in capsule (AIC) | 3 |
| AIC 4.0 mg CC-122 administered orally at a dose of 4.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using active ingredient in capsule (AIC) | 3 |
| F6 3.0 mg CC-122 administered orally at a dose of 3.0 mg on a 5 continuous days out of 7 days per week intermittent dosing schedule using formulated capsules (F6) | 6 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 1 |
| Overall Study | Progressive disease | 2 | 2 | 1 | 5 |
| Overall Study | Study terminated by Sponsor | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | AIC 2.0 mg | AIC 3.0 mg | AIC 4.0 mg | F6 3.0 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 61.7 Years STANDARD_DEVIATION 4.51 | 62 Years STANDARD_DEVIATION 14.53 | 68.7 Years STANDARD_DEVIATION 8.62 | 65.3 Years STANDARD_DEVIATION 7.5 | 64.6 Years STANDARD_DEVIATION 8.42 |
| Race/Ethnicity, Customized Primary Race Japanese | 3 Participants | 3 Participants | 3 Participants | 6 Participants | 15 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 0 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 0 / 3 | 0 / 3 | 1 / 6 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 1 / 3 | 2 / 6 |
Outcome results
Primary
Accumulation Index of CC-122
Accumulation Index defined as AUCtau (Cycle 1 Day 10, 11 or 12)/AUCtau (Cycle 1 Day 1)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Population: Pharmacokinetics (PK) population: The PK Evaluable Population includes all participants who take at least one dose of CC- 122, and have at least one measurable CC- 122 concentration datum.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AIC 2.0 mg | Accumulation Index of CC-122 | 1.41 ng/mL*h | Geometric Coefficient of Variation 9.3 |
| AIC 3.0 mg | Accumulation Index of CC-122 | 1.26 ng/mL*h | Geometric Coefficient of Variation 8.3 |
| AIC 4.0 mg | Accumulation Index of CC-122 | 1.47 ng/mL*h | Geometric Coefficient of Variation 9 |
| F6 3.0 mg | Accumulation Index of CC-122 | 1.25 ng/mL*h | Geometric Coefficient of Variation 24.6 |
Primary
Maximum Tolerated Dose (MTD)
The MTD is defined as the last dose level below the non-tolerated dose (NTD) with zero or one out of six evaluable participants experiencing dose-limiting toxicities (DLTs) during the DLT evaluation period. At least 6 participants will be enrolled at the MTD/recommended phase 2 dose (RP2D). MTD will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria Version 4.03
Time frame: From first dose up to at least 28 days (Cycle 1)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AIC 2.0 mg | Maximum Tolerated Dose (MTD) | 4.0 mg |
Primary
Number of Participants With Dose-Limiting Toxicities (DLTs)
NCI CTCAE Version 4.03 will be used to grade adverse events. Events described below will be classified as DLTs: * Non-hematologic AEs: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3 * Laboratory abnormalities: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3 * Hematologic: Any febrile neutropenia, Grade 4 neutropenia lasting \> 7 days, Grade 4 thrombocytopenia lasting \> 24 hours or thrombocytopenia of any grade requiring platelet transfusions, Any Grade 3/4 thrombocytopenia with clinically significant bleeding * Hepatic: Grade 4 liver function tests or Grade 3 ALT with Grade 2 or higher bilirubin will be considered a DLT, irrespective of underlying attribution. Other Grade 3 LFTs due to disease progression in the liver will not be considered DLTs * Other adverse events: Suspected to be related to CC-122 and necessitating a dose reduction during the DLT evaluation period
Time frame: From first dose up to at least 28 days (Cycle 1)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AIC 2.0 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| AIC 3.0 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| AIC 4.0 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| F6 3.0 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | 1 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria version 4.03
Time frame: From first dose to 28 days post last dose of investigational product (Up to approximately 92 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AIC 2.0 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| AIC 3.0 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| AIC 4.0 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| F6 3.0 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
Primary
Pharmacokinetic Parameters of CC-122: AUC0-t
Area under the plasma concentration time-curve up to the last measurable concentration (AUC0-t)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Population: Pharmacokinetics (PK) population: The PK Evaluable Population includes all participants who take at least one dose of CC- 122, and have at least one measurable CC- 122 concentration datum.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: AUC0-t | Cycle 1 Day 1 | 634.70 ng/mL*h | Geometric Coefficient of Variation 39.2 |
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: AUC0-t | Cycle 1 Day 10, 11, or 12 | 895.49 ng/mL*h | Geometric Coefficient of Variation 45.7 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: AUC0-t | Cycle 1 Day 10, 11, or 12 | 744.65 ng/mL*h | Geometric Coefficient of Variation 4.9 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: AUC0-t | Cycle 1 Day 1 | 590.30 ng/mL*h | Geometric Coefficient of Variation 6.2 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: AUC0-t | Cycle 1 Day 1 | 953.89 ng/mL*h | Geometric Coefficient of Variation 11 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: AUC0-t | Cycle 1 Day 10, 11, or 12 | 1399.3 ng/mL*h | Geometric Coefficient of Variation 2.6 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: AUC0-t | Cycle 1 Day 1 | 982.59 ng/mL*h | Geometric Coefficient of Variation 35.9 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: AUC0-t | Cycle 1 Day 10, 11, or 12 | 1282.80 ng/mL*h | Geometric Coefficient of Variation 27.9 |
Primary
Pharmacokinetic Parameters of CC-122: AUCtau
Area under the plasma concentration time-curve during a dosing interval (AUCtau)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Population: Pharmacokinetics (PK) population: The PK Evaluable Population includes all participants who take at least one dose of CC- 122, and have at least one measurable CC- 122 concentration datum.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: AUCtau | Cycle 1 Day 1 | 634.70 ng/mL*h | Geometric Coefficient of Variation 39.2 |
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: AUCtau | Cycle 1 Day 10, 11, or 12 | 895.49 ng/mL*h | Geometric Coefficient of Variation 45.7 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: AUCtau | Cycle 1 Day 10, 11, or 12 | 744.65 ng/mL*h | Geometric Coefficient of Variation 4.9 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: AUCtau | Cycle 1 Day 1 | 590.3 ng/mL*h | Geometric Coefficient of Variation 6.2 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: AUCtau | Cycle 1 Day 1 | 953.89 ng/mL*h | Geometric Coefficient of Variation 11 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: AUCtau | Cycle 1 Day 10, 11, or 12 | 1399.3 ng/mL*h | Geometric Coefficient of Variation 2.6 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: AUCtau | Cycle 1 Day 1 | 982.59 ng/mL*h | Geometric Coefficient of Variation 35.9 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: AUCtau | Cycle 1 Day 10, 11, or 12 | 1282.8 ng/mL*h | Geometric Coefficient of Variation 27.9 |
Primary
Pharmacokinetic Parameters of CC-122: CL/F
Apparent clearance (CL/F)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Population: Pharmacokinetics (PK) population: The PK Evaluable Population includes all participants who take at least one dose of CC- 122, and have at least one measurable CC- 122 concentration datum.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: CL/F | Cycle 1 Day 1 | 2.84 L/h | Geometric Coefficient of Variation 35.6 |
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: CL/F | Cycle 1 Day 10, 11 or 12 | 1.55 L/h | Geometric Coefficient of Variation 59.6 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: CL/F | Cycle 1 Day 10, 11 or 12 | 2.63 L/h | Geometric Coefficient of Variation 7.5 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: CL/F | Cycle 1 Day 1 | 4.11 L/h | Geometric Coefficient of Variation 3.8 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: CL/F | Cycle 1 Day 1 | 3.17 L/h | Geometric Coefficient of Variation 15.8 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: CL/F | Cycle 1 Day 10, 11 or 12 | 2.12 L/h | Geometric Coefficient of Variation 6.2 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: CL/F | Cycle 1 Day 1 | 2.53 L/h | Geometric Coefficient of Variation 34.6 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: CL/F | Cycle 1 Day 10, 11 or 12 | 1.9 L/h | Geometric Coefficient of Variation 30.1 |
Primary
Pharmacokinetic Parameters of CC-122: Cmax
Peak (maximum) plasma concentration (Cmax)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Population: Pharmacokinetics (PK) population: The PK Evaluable Population includes all participants who take at least one dose of CC- 122, and have at least one measurable CC- 122 concentration datum.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: Cmax | Cycle 1 Day 1 | 52.78 ng/mL | Geometric Coefficient of Variation 30.4 |
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: Cmax | Cycle 1 Day 10,11 or 12 | 72.13 ng/mL | Geometric Coefficient of Variation 34.6 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: Cmax | Cycle 1 Day 10,11 or 12 | 58.88 ng/mL | Geometric Coefficient of Variation 28.6 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: Cmax | Cycle 1 Day 1 | 52.26 ng/mL | Geometric Coefficient of Variation 17.4 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: Cmax | Cycle 1 Day 1 | 73.8 ng/mL | Geometric Coefficient of Variation 20 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: Cmax | Cycle 1 Day 10,11 or 12 | 112.61 ng/mL | Geometric Coefficient of Variation 24.5 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: Cmax | Cycle 1 Day 1 | 107.72 ng/mL | Geometric Coefficient of Variation 42.3 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: Cmax | Cycle 1 Day 10,11 or 12 | 113.54 ng/mL | Geometric Coefficient of Variation 28.7 |
Primary
Pharmacokinetic Parameters of CC-122: t1/2
Terminal half-life of CC-122 (t1/2)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Population: Pharmacokinetics (PK) population: The PK Evaluable Population includes all participants who take at least one dose of CC- 122, and have at least one measurable CC- 122 concentration datum.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: t1/2 | Cycle 1 Day 1 | 11.67 hours | Geometric Coefficient of Variation 19.8 |
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: t1/2 | Cycle 1 Day 10, 11 or 12 | 13.51 hours | Geometric Coefficient of Variation 28.4 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: t1/2 | Cycle 1 Day 10, 11 or 12 | 15.5 hours | Geometric Coefficient of Variation 3 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: t1/2 | Cycle 1 Day 1 | 9.98 hours | Geometric Coefficient of Variation 19.2 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: t1/2 | Cycle 1 Day 1 | 11.67 hours | Geometric Coefficient of Variation 12.3 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: t1/2 | Cycle 1 Day 10, 11 or 12 | 12.36 hours | Geometric Coefficient of Variation 11.4 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: t1/2 | Cycle 1 Day 1 | 9.27 hours | Geometric Coefficient of Variation 29.9 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: t1/2 | Cycle 1 Day 10, 11 or 12 | 9.7 hours | Geometric Coefficient of Variation 19.6 |
Primary
Pharmacokinetic Parameters of CC-122: Tmax
Time to maximum plasma concentration (Tmax)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Population: Pharmacokinetics (PK) population: The PK Evaluable Population includes all participants who take at least one dose of CC- 122, and have at least one measurable CC- 122 concentration datum.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: Tmax | Cycle 1 Day 1 | 2.24 hours | Geometric Coefficient of Variation 78.8 |
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: Tmax | Cycle 1 Day 10, 11 or 12 | 1.65 hours | Geometric Coefficient of Variation 60.1 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: Tmax | Cycle 1 Day 10, 11 or 12 | 1.55 hours | Geometric Coefficient of Variation 166.4 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: Tmax | Cycle 1 Day 1 | 1.5 hours | Geometric Coefficient of Variation 78.5 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: Tmax | Cycle 1 Day 1 | 1.19 hours | Geometric Coefficient of Variation 41.7 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: Tmax | Cycle 1 Day 10, 11 or 12 | 1.5 hours | Geometric Coefficient of Variation 78.5 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: Tmax | Cycle 1 Day 1 | 0.88 hours | Geometric Coefficient of Variation 46.1 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: Tmax | Cycle 1 Day 10, 11 or 12 | 1.28 hours | Geometric Coefficient of Variation 73.3 |
Primary
Pharmacokinetic Parameters of CC-122: Vz/F
Apparent volume of distribution (Vz/F)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Population: Pharmacokinetics (PK) population: The PK Evaluable Population includes all participants who take at least one dose of CC- 122, and have at least one measurable CC- 122 concentration datum.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: Vz/F | Cycle 1 Day 1 | 47.75 L | Geometric Coefficient of Variation 15 |
| AIC 2.0 mg | Pharmacokinetic Parameters of CC-122: Vz/F | Cycle 1 Day 10, 11, or 12 | 30.29 L | Geometric Coefficient of Variation 37.4 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: Vz/F | Cycle 1 Day 1 | 59.11 L | Geometric Coefficient of Variation 18.6 |
| AIC 3.0 mg | Pharmacokinetic Parameters of CC-122: Vz/F | Cycle 1 Day 10, 11, or 12 | 58.78 L | Geometric Coefficient of Variation 4.5 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: Vz/F | Cycle 1 Day 10, 11, or 12 | 37.82 L | Geometric Coefficient of Variation 5.2 |
| AIC 4.0 mg | Pharmacokinetic Parameters of CC-122: Vz/F | Cycle 1 Day 1 | 53.46 L | Geometric Coefficient of Variation 8.5 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: Vz/F | Cycle 1 Day 10, 11, or 12 | 26.64 L | Geometric Coefficient of Variation 31.4 |
| F6 3.0 mg | Pharmacokinetic Parameters of CC-122: Vz/F | Cycle 1 Day 1 | 33.80 L | Geometric Coefficient of Variation 46.2 |
Secondary
Best Overall Response (BOR)
BOR by investigator is defined according to International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma for NHL patients and Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for solid tumors patients. For NHL, complete remission (CR)=disappearance of all evidence of disease. Partial response (PR)=regression of measurable disease and no new sites. Stable disease (SD)=failure to attain CR/PR or PD. Progressive disease (PD)=any new lesion or increase by \>=50% of previously sites from nadir. For solid tumors, complete response (CR)=disappearance of all target and non-target lesions and no new lesions. PR=at least a 30% decrease in the sum of diameters of target lesions and no new lesions. SD=neither sufficient shrinkage to qualify for PR or increase to qualify for PD. PD=at least 20% increase in the sum of diameters of target lesions from nadir.
Time frame: From first dose until objectively documented progression (Up to 92 Months) at Day 15 of Cycle 2, 4, 6, and every 3 cycles thereafter (Cycle = 28 Days)
Population: Efficacy Evaluable (EE) population: all participants who complete at least one cycle of their assigned treatment regimen, and have a baseline and at least one post-baseline efficacy assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AIC 2.0 mg | Best Overall Response (BOR) | NHL Complete Remission | 1 Participants |
| AIC 2.0 mg | Best Overall Response (BOR) | NHL Partial Response (PR) | 1 Participants |
| AIC 2.0 mg | Best Overall Response (BOR) | NHL Stable Disease (SD) | 0 Participants |
| AIC 2.0 mg | Best Overall Response (BOR) | NHL Progressive Disease (PD) | 0 Participants |
| AIC 2.0 mg | Best Overall Response (BOR) | Solid Tumors Complete Response | 0 Participants |
| AIC 2.0 mg | Best Overall Response (BOR) | Solid Tumors PR | 0 Participants |
| AIC 2.0 mg | Best Overall Response (BOR) | Solid Tumors SD | 0 Participants |
| AIC 2.0 mg | Best Overall Response (BOR) | Solid Tumors PD | 1 Participants |
| AIC 3.0 mg | Best Overall Response (BOR) | Solid Tumors PR | 0 Participants |
| AIC 3.0 mg | Best Overall Response (BOR) | Solid Tumors Complete Response | 0 Participants |
| AIC 3.0 mg | Best Overall Response (BOR) | NHL Partial Response (PR) | 1 Participants |
| AIC 3.0 mg | Best Overall Response (BOR) | Solid Tumors PD | 0 Participants |
| AIC 3.0 mg | Best Overall Response (BOR) | Solid Tumors SD | 0 Participants |
| AIC 3.0 mg | Best Overall Response (BOR) | NHL Progressive Disease (PD) | 0 Participants |
| AIC 3.0 mg | Best Overall Response (BOR) | NHL Stable Disease (SD) | 1 Participants |
| AIC 3.0 mg | Best Overall Response (BOR) | NHL Complete Remission | 1 Participants |
| AIC 4.0 mg | Best Overall Response (BOR) | Solid Tumors SD | 0 Participants |
| AIC 4.0 mg | Best Overall Response (BOR) | NHL Stable Disease (SD) | 0 Participants |
| AIC 4.0 mg | Best Overall Response (BOR) | NHL Progressive Disease (PD) | 0 Participants |
| AIC 4.0 mg | Best Overall Response (BOR) | Solid Tumors Complete Response | 0 Participants |
| AIC 4.0 mg | Best Overall Response (BOR) | Solid Tumors PR | 0 Participants |
| AIC 4.0 mg | Best Overall Response (BOR) | Solid Tumors PD | 0 Participants |
| AIC 4.0 mg | Best Overall Response (BOR) | NHL Complete Remission | 2 Participants |
| AIC 4.0 mg | Best Overall Response (BOR) | NHL Partial Response (PR) | 1 Participants |
| F6 3.0 mg | Best Overall Response (BOR) | NHL Stable Disease (SD) | 2 Participants |
| F6 3.0 mg | Best Overall Response (BOR) | NHL Progressive Disease (PD) | 2 Participants |
| F6 3.0 mg | Best Overall Response (BOR) | NHL Partial Response (PR) | 1 Participants |
| F6 3.0 mg | Best Overall Response (BOR) | NHL Complete Remission | 0 Participants |
| F6 3.0 mg | Best Overall Response (BOR) | Solid Tumors Complete Response | 0 Participants |
| F6 3.0 mg | Best Overall Response (BOR) | Solid Tumors PD | 0 Participants |
| F6 3.0 mg | Best Overall Response (BOR) | Solid Tumors SD | 0 Participants |
| F6 3.0 mg | Best Overall Response (BOR) | Solid Tumors PR | 0 Participants |
Secondary
Duration of Response (DoR)
DoR for NHL patients is defined as the time from the date when complete response (CR) or partial response (PR), whichever is first recorded are met, until the date when disease progression (PD) is first objectively documented, or the date of the last adequate tumor assessment when no disease progression is documented throughout the study according to International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR=disappearance of all evidence of disease. PR=regression of measurable disease and no new sites. Progressive disease (PD)=any new lesion or increase by \>=50% of previously sites from nadir.
Time frame: From first dose until objectively documented progression (Up to 92 Months) at Day 15 of Cycle 2, 4, 6, and every 3 cycles thereafter (Cycle = 28 Days)
Population: Efficacy Evaluable (EE) population with complete response (CR) or partial response (PR): all participants who complete at least one cycle of their assigned treatment regimen, and have a baseline and at least one post-baseline efficacy assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AIC 2.0 mg | Duration of Response (DoR) | NA weeks |
| AIC 3.0 mg | Duration of Response (DoR) | NA weeks |
| AIC 4.0 mg | Duration of Response (DoR) | 139.4 weeks |
| F6 3.0 mg | Duration of Response (DoR) | 39.9 weeks |