Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Avadomide (CC-122), CC-122, BMS-986381
Avadomide · 7 trials · 12 indications
Frequency of dose-limiting toxicities (DLTs) associated with the addition of avadomide (CC-122) to R-CHOP-21 therapy
CR is defined as target nodes/nodal masses regress to ≤ 1.5 cm in LDi; no extralymphatic sites of disease; no measurable lesions, no organ enlargement and normal morphology on bone marrow (BM) exam; immunohistochemically (IHC) negative
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
Number of participants with adverse events
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 | - |
| Avadomide (CC-122) plus R-CHOP-21 | EXPERIMENTAL | Avadomide (CC-122) by mouth (PO) at varying dose levels (Ph 1) on Days 1 through 5 and Days 8 through 12 plus Rituxan 375 mg/m2 by intravenous (IV) infusion, cyclophosphamide 750mg/m2 by IV infusion, doxorubicin 50 mg/m2 IV, vincristine 1.4 mg/m2 (max is 2.0 mg) IV and 100 mg PO prednisone/prednisolone on Days 1 through 5 of each 21-day treatment cycles for up to 6 total treatment cycles (approximately 18 weeks or 4 months) |
| 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. |
| 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 |
| Avadomide (CC-122) | DRUG | Avadomide (CC-122) by mouth at the assigned dose in Ph 1 starting on Day 1 for 5 consecutive days per week, followed by 2 days without avadomide (CC-122) administration (5/7) for the first two weeks of a 21-day treatment cycle. If the highest proposed dose level to be explored in Phase 1 is applied, the dosing regimen will be 5/7 days for all 3 weeks of each 21-day treatment cycle. |
| Rituximab | DRUG | Rituxan 375 mg/m2 on Day 1 by intravenous (IV) infusion of a 21-day treatment cycle for up to a total of 6 cycles |
| Cyclophosphamide 750mg/m2 by IV infusion | DRUG | Cyclophosphamide 750mg/m2 on Day 1 by IV infusion of a 21-day treatment cycle for up to a total of 6 cycles |
| Vincristine | DRUG | Vincristine 1.4 mg/m2 (maximum of 2.0 mg total) on Day 1 by IV bolus on Day 1 of a 21-day treatment cycle for up to a total of 6 cycles |
| Prednisone | DRUG | Prednisone 100 mg PO on Days 1 through 5 of each 21-day treatment or 100mg IV on Day 1 is also acceptable for up to a total of 6 cycles |
| 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...
Avadomide is an investigational small molecule being studied for diffuse B-cell lymphoma, a type of non-Hodgkin lymphoma. It has been evaluated in a Phase 1 trial in combination with RCHOP chemotherapy for newly diagnosed diffuse large B-cell lymphoma (DLBCL) with poor risk factors. It is not approved for any indication.
Avadomide targets cereblon, a protein that is part of the E3 ubiquitin ligase complex. It belongs to the -domide class of compounds, which modulate cereblon activity to promote degradation of specific proteins. This mechanism is being investigated for its potential anti-lymphoma effects in diffuse B-cell lymphoma.
Avadomide is being developed by Bristol-Myers Squibb Company (ticker: BMY). The company is responsible for its clinical development in oncology, specifically for diffuse B-cell lymphoma.
Avadomide is in Phase 1 clinical development. It is investigational and has not been approved by the FDA or any regulatory agency for any indication. The Phase 1 trial for diffuse B-cell lymphoma has been completed.
Avadomide has been studied in one clinical trial: NCT03283202, titled "Study of Safety and Efficacy of Avadomide (CC-122) Combined With RCHOP for Newly-diagnosed DLBCL With Poor Risk Factors." This Phase 1 trial enrolled 35 participants across the United States, Belgium, Canada, and Spain, and is now completed.
Yes, Avadomide is also known as CC-122. Both names refer to the same investigational compound developed by Bristol-Myers Squibb for diffuse B-cell lymphoma.