Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
CC-122 · 8 trials · 13 indications
Observed maximum plasma concentration
Area under the plasma concentration-time curve calculated from time zero extrapolated to infinity
Time to Observed maximum serum concentration (Cmax)
Observed maximum serum concentration (Cmax)
Area under the serum concentration-time curve calculated from time zero to the last measured time point
Area under the serum concentration-time curve calculated from time zero to infinity
Terminal elimination half-life
Apparent clearance of drug from serum when dosed orally
Apparent volume of distribution when dosed subcutaneously during the terminal phase
Renal Clearance
Amount of excretion
During dose escalation, the DLT assessment period is defined as Days 1 to 28 of Cycle 1 including the predose assessments specified for Day 1 of Cycle 2. A DLT is defined as any of the following toxicities occurring within the DLT assessment window unless the event can clearly be determined to be unrelated to the drug.
During dose escalation, the TEAE phase 1 assessment period is defined as Days 1 to 28 of Cycle 1 including the predose assessments specified for Day 1 of Cycle 2. Number of participants who experienced a TEAE during the course of the study.
ORR is is defined as the number and percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR).
Number and severity of adverse events using the NCI CTCAE criteria (version 4.03), including DLTs
Determination of the NTD and MTD in CC-122 in combination with ibrutinib and CC-122 in combination with obinutuzumab
Biological matrices (whole blood, plasma, urine and feces) will be collected and analyzed for total \[14C\]-radioactivity
Urine and feces will be collected and analyzed for measurement of \[14C\]-radioactivity
Blood samples will be collected and analyzed for measurement of \[14C\]-radioactivity
Biological matrices (plasma, urine, and fecal samples) will be collected and select samples will undergo metabolite profiling/characterization
Blood samples will be collected and analyzed; Maximum observed plasma or whole blood concentration for up to 168 hours postdose will be calculated and reported as appropriate
Blood samples will be collected and analyzed; Area under the concentration-time curve from time zero up to 168 hours postdose will be calculated and reported as appropriate
Blood samples will be collected and analyzed; Time to reach the observed maximum (peak) concentration will be calculated and reported as appropriate.
Blood samples will be collected and analyzed; Terminal half-life will be calculated and reported as appropriate
Area under the plasma concentration-time curve
Dose-limiting toxicities (DLTs) will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE): * A clinically relevant AE that is suspected to be related to CC-122 and starts ≤ 30 days of first dose (Cycle 1) and ≥ grade (Gr) 3 except for Alopecia, Gr3 rash of the acneiform or maculopapular type \< 4 daysduration , Gr 3 diarrhea or vomiting lasting\< 72 hours * Clinically relevant laboratory abnormality suspected to be related to CC-122 and that commences within 30 days of first dose and ≥ Gr3. * Hematological toxicities as follows: Any febrile neutropenia (NP), Gr4 NP \> 7 days, Gr 4 thrombocytopenia \> 24 hours, Any Gr 3/4 thrombocytopenia with clinically significant bleeding. * Gr 4 liver function tests (LFTs) or Gr 3 ALT with ≥ Gr2 bilirubin * Any AE suspected to be CC-122 related and necessitating dose reduction during Cycle 1.
Maximum observed concentration in plasma (Cmax)
Area under the concentration-time curve
Time to maximum concentration
Terminal half-life
Apparent total body clearance
Apparent volume of distribution
Is defined as the dose level at which ≥2 out of 6 evaluable subjects in any dose cohort with DLT.
Is defined as the last dose level below the NTD with ≤1 out of 6 evaluable subjects with DLT) during Cycle (C) 1.
| Arm | Type | Description |
|---|---|---|
| CC-122 and Dexamethasone | EXPERIMENTAL | - |
| CC-122 Alone under fasted conditions | EXPERIMENTAL | Single oral dose of 3 mg CC-122 administered alone under fasted conditions |
| CC-122 plus Itraconazole | EXPERIMENTAL | Single oral dose of 3 mg CC-122 alone and with multiple doses of itraconazole. |
| CC-122 plus Fluvoxamine | EXPERIMENTAL | Single oral dose of 3 mg CC-122 alone and with multiple doses of fluvoxamine. |
| CC-122 plus Rifampin | EXPERIMENTAL | Single oral dose of 3 mg CC-122 alone and with multiple doses of rifampin |
| Single oral dose of 3 mg CC-122 | EXPERIMENTAL | All subjects will receive one 3 mg CC-122 capsule the morning of Day 1 which will be administered in the fasted state. |
| CC-122 with Nivolumab | EXPERIMENTAL | CC-122 orally 5/7 days with nivolumab Intravenously (IV) 3mg/kg every 2 weeks. Cohorts of up to 6 subjects per dose level until Recommended Phase 2 dose (RP2D). |
| CC-122 Single Agent | EXPERIMENTAL | An intrasubject dose escalation design was selected to determine the safety of single agent CC-122 (Arm A) in order to reach an optimal, clinically active dose and to mitigate the risk of early tumor flare reactions, based on earlier experience with lenalidomide monotherapy in CLL. |
| CC-122 in combination with ibrutinib | EXPERIMENTAL | Ascending fixed dose cohorts evaluated in a 3 + 3 dose-finding design will be used to determine the safety and tolerability of the combination of CC-122 and ibrutinib to determine the NTD, MTD, and Recommended Phase 2 Dose (RP2D). An intrasubject dose escalation cohort may also be evaluated at the discretion of the Safety Review Committee. The RP2D of the combination may be evaluated in ibrutinib-naïve and high-risk CLL patients in the dose expansion phase to continue to evalute safety and efficacy. |
| CC-122 in combination with obinutuzumab | EXPERIMENTAL | Ascending fixed dose cohorts evaluated in a 3 + 3 dose-finding design will be used to determine the safety and tolerability of the combination of CC-122 and obinutuzumab to determine the , MTD, and Recommended Phase 2 Dose (RP2D). An intrasubject dose escalation cohort may also be evaluated at the discretion of the Safety Review Committee.. The RP2D of the combination may be evaluated in CLL patients who failed a B-cell receptor pathway inhibitor or venetoclax in the dose expansion phase to continue to evalute safety and efficacy. |
| 3mg [14C]-CC-122 (Single Dose) | EXPERIMENTAL | Single oral capsule of 3mg \[14C\]-CC-122. given as a suspension under fasting conditions on Day 1 |
| 3 mg CC-122 reference capsule formulation | EXPERIMENTAL | 3 mg CC-122 reference capsule given by mouth with 240 mL of room temp tap water |
| 3 mg CC-122 test capsule formulation | EXPERIMENTAL | 3 mg CC-122 test capsule give by mouth with 240 mL of room temp tap water |
| 3 mg CC-122 test capsule + high fat meal | EXPERIMENTAL | 3 mg CC-122 test capsule given by mouth with 240 mL of room temp tap water approximately 5 minutes after eating a high-fat meal |
| CC-122 MM-2 | EXPERIMENTAL | A new MM cohort (MM-2) will be enrolled in order to evaluate tolerability, safety and preliminary efficacy of the CC-122 formulated capsule given on an intermittent schedule (5/7 days per week) in 2 parallel dose escalation cohorts (MM-2a and MM-2b, respectively) (DEX) in Pomalidomide naïve subjects |
| CC-122- DLBCL-2 | EXPERIMENTAL | A new DLBCL cohort (DLBCL-2) in order to evaluate intermittent schedules of CC-122 (5 continuous days out of 7 days per week \[5/7 days\] and/or 21 continuous days out of 28 days per cycle \[21/28 days\]). Doses to be explored include 4 mg and 5 mg on an intermittent schedule using the 3+3 design described in Part A in order to establish an MTD for the intermittent dosing schedules. Following dose escalation, one or more intermittent dosing schedules may be expanded at or below the new intermittent schedule MTD in at least 20 total subjects per dosing schedule. |
| CC-122- GBM-2 | EXPERIMENTAL | A new GBM cohort (GBM-2) in order to evaluate doses of CC-122 above the 3 mg QD MTD determined in all comers in Part A. CC-122 dose will increase in 1 mg increments starting with 4 mg daily on a continuous schedule using the 3+3 design described in Part A in order to establish an MTD specific for GBM subjects. Following dose escalation, the cohort will be expanded at or below the new MTD in up to 20 total subjects. |
| Primary Central Nervous System Lymphoma (PCNSL) | EXPERIMENTAL | During dose expansion of selected intermittent schedules, an additional cohort of up to 10 subjects with PCNSL will also be explored at the same dose and schedule as DLBCL to confirm some safety and preliminary efficacy signal |
| Name | Type | Description |
|---|---|---|
| CC-122 | DRUG | Specified dose on specified days |
| Dexamethasone | DRUG | Specified dose on specified days |
| Itraconazole | DRUG | CYP3A Inhibitor |
| Fluvoxamine | DRUG | CYP1A2 Inhibitor |
| Rifampin | DRUG | CYP3A Inducer |
| Nivolumab | DRUG | - |
| Ibrutinib | DRUG | - |
| Obinutuzumab | DRUG | Obinutuzumab will be administered as an intravenous (IV) infusion at a dose of 100 mg on Cycle 1 Day 1 and 900 mg on Cycle 1 Day 2 and 1000 mg on Cycle 1 Days 8 and 15. The dose of obinutuzumab on Days 1 and 2 of Cycle 1 may be adjusted per institutional practice as long as the combined dose equals 1000 mg. Obinutuzumab will be administered at a dose of 1000 mg on Day 1 of Cycles 2 through 6. |
Key Inclusion Criteria: * Participant who is currently receiving CC-122 on another CC-122 clinical trial that has met its primary and secondary endpoints. * Participant who has participated in previous CC-122 protocol (including CC-122-ST-001 \[NCT01421524\], CC-122-ST-002 \[NCT02509039\], CC-122-D...
CC-122 is an investigational small molecule being studied for use in oncology. Its clinical development includes studies in Non-Hodgkin Lymphoma, Multiple Myeloma, Carcinoma, and Hepatocellular conditions. It has also been evaluated in healthy volunteers for clinical pharmacology studies. CC-122 is not approved and remains in clinical development.
CC-122 is being developed by Bristol-Myers Squibb Company, which trades under the ticker BMY. The company is conducting clinical trials to evaluate the drug's safety and pharmacokinetics in various patient populations and healthy subjects.
CC-122 is in Phase 1 clinical development. All recorded trials for CC-122 are Phase 1 studies, including completed pharmacokinetic studies in healthy volunteers and an active rollover study in patients with Non-Hodgkin Lymphoma. The drug is investigational and has not been approved by regulatory authorities.
CC-122 has been studied in several clinical trials, including NCT02049528, a pharmacokinetic study in healthy male volunteers; NCT02234999, a radiolabeled study in healthy subjects; NCT02406742, a Phase 1/2 combination study with ibrutinib and obinutuzumab in chronic lymphocytic leukemia; and NCT05688475, an active rollover study in Non-Hodgkin Lymphoma.
CC-122 is also known by its code name CC-122. No alternative brand names or generic names have been disclosed for this investigational agent. It is being studied under this identifier across clinical trials registered by Bristol-Myers Squibb.