CC-220

The primary objective is to evaluate the clinical efficacy of three doses of CC-220 (0.45 mg once per day \[QD\], 0.3 mg QD or 0.15 mg QD) compared to placebo, for the treatment of active systemic lupus erythematosus (SLE) using the SLE Responder Index at Week 24 Composite endpoint SRI(4), defined by the following criteria: - Reduction from Baseline of ≥ 4 points in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K score and - No new one or more British Isles Lupus Assessment Group (BILAG) A or new (excludes A to B) 2 or more BILAG B items compared to Baseline using BILAG 2004 Index and - No worsening from Baseline defined by an increase of \< 0.30 points from Baseline on a Physician's Global Assessment (PGA) visual analog scale (VAS) from 0-3

A TEAE was defined as any adverse event (AE) that began or worsened on or after the start of IP up to 28 days after the last dose of IP or IP discontinuation date, whichever was later. Each participant was counted once for each applicable category. An IP-related TEAE was defined as a TEAE that the investigator considered to be of suspected relationship to IP. The severity of each adverse event and serious AE (SAE) was assessed by the investigator and graded based on a scale from mild - mild symptoms to severe AEs (non-serious or serious). A serious adverse event (SAE) was any AE which: • Resulted in death • Was life-threatening • Required inpatient hospitalization or prolongation of existing hospitalization • Resulted in persistent or significant disability/incapacity • Was a congenital anomaly/birth defect • Constituted an important medical event.

A TEAE was defined as any adverse event (AE) that began or worsened on or after the start of IP through 28 days after the last dose of IP or IP discontinuation date, whichever was later. Each participant was counted once for each applicable category. An IP-related TEAE was defined as a TEAE that the investigator considered to be of suspected relationship to IP. The severity of each adverse event and serious AE (SAE) was assessed by the investigator and graded based on a scale from mild - mild symptoms to severe AEs (non-serious or serious). A serious adverse event (SAE) was any AE which: • Resulted in death • Was life-threatening • Required inpatient hospitalization or prolongation of existing hospitalization • Resulted in persistent or significant disability/incapacity • Was a congenital anomaly/birth defect • Constituted an important medical event.

Frequency of dose-limiting toxicities (DLT) associated with addition of iberdomide (CC-220) to R-CHOP-21 therapy and the addition of CC-99282 to R-CHOP-21 therapy

Defined as the dose that will be selected for dose expansion based on MTD

AEs evaluated using NCI CTCAE criteria, v. 5.0, including treatment -emergent adverse events (TEAEs) and laboratory assessments

Frequency of DLTs associated with addition of iberdomide (CC-220) to polatuzumab-R-CHP therapy and the addition of CC-99282 to polatuzumab-R-CHP therapy

Defined as the dose that will be selected for dose expansion based on MTD

Estimation of AUC calculated from time zero to the last measured time point

Estimation of AUC calculated from time zero to infinity

Estimation of observed maximum concentration

Estimation of time to Cmax

Estimation of terminal elimination half-life

Estimation of apparent clearance of drug from plasma after extravascular administration

Estimation of apparent volume of distribution during the terminal phase

Total \[14C\]-RA in whole blood, plasma, urine, and feces (and vomit, if applicable) will be measured via AMS.

Total RA recovery will be computed as the sum of the cumulative excretion (as % dose) in urine and feces (and vomit, if applicable).

Total \[14C\]-RA in whole blood and plasma will be converted to ngEq/mL concentration of \[14C\]-CC-220 based on specific activity of the dose.

Percentage of the administered dose attributed to CC-220 and metabolite(s), and the RA of \[14C\]-CC-220 and metabolite(s), as appropriate, will be estimated.

Observed maximum plasma concentration, provided sufficient data available

Area under the concentration-time curve, provided sufficient data available

Time to Cmax, provided sufficient data available

Terminal elimination half-life, provided sufficient data available

Observed maximum plasma concentration

Area under the concentration-time curve calculated from time zero to the last measured time point

The dose-limiting toxicity (DLT) population includes subjects who missed no more than 4 doses of CC-220, 2 doses of DEX, 1 dose of IV DARA (Cohort E), 1 dose of BTZ (Cohort F), or 1 dose of CFZ (Cohort G1 or G2) during Cycle 1 for reasons other than DLT. This population will be used for analyzing the primary endpoint regarding the determination of the MTD. Hematologic DLTs: Grade 4 neutropenia (ANC \<500/μL for \>5 days) Grade 3 neutropenia (ANC \<1,000/μL) with fever ≥38.5°C Grade 4 thrombocytopenia (platelet count \<25,000/μL) or Grade 3 thrombocytopenia with bleeding or need for platelet transfusion Any other grade 4 hematologic toxicity, except anemia, not resolving to pretreatment baseline within 72 hours. Non-hematologic DLT: Any non-hematological toxicity ≥ Grade 3, except alopecia and nausea controlled by medical management.

Tumor response, including progressive disease (PD) according to the IMWG Uniform Response Criteria (Kumar, 2016) for subjects who achieved partial response (PR) or better.

Maximum plasma concentration

Area under the plasma concentration from time zero extrapolated to infinity

Number of participants with adverse events

Blood samples will be collected at pre-specified times to determine levels of CC-220 free base and its R-enantiomer in plasma