A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma

Subjects assigned to CC-220 monotherapy, who develop progressive disease (PD) will have

the option to receive DEX in addition to CC-220 after consultation with the Medical

Monitor. The dose of CC-220 will not be higher than the dose of CC-220 used in

combination with dexamethasone in Cohort B that has been determined to be safe.

Progressive disease must be confirmed in accordance with international myeloma working

group (IMWG) criteria.

For Cohorts A and B, the starting dose level of CC-220, dose level 1, is 0.3 mg. A dose

level -1, of 0.15 mg, may also be evaluated if the starting dose level of 0.3 mg for 21

days of a 28-day cycle is not tolerated. For Cohorts E and F, the starting dose level of

CC-220, dose level 1, is one dose level below the maximum dose for Cohort B that has been

determined to be safe by the dose escalation committee (DEC) at the start of enrollment

for both cohorts. For Cohort E in addition to CC-220 and DEX, daratumumab will be

administered intravenously (IV) at a 16mg/kg dose. For Cohort F in addition to CC-220 and

DEX, bortezomib will be administered subcutaneous (SC) at a 1.3mg/m2 dose.

All subjects who discontinue study treatment in Part 1 or Part 2 of the study for a

reason other than PD or withdrawal of consent from the study will be followed for

response assessment every 28 days (every 21 days for Cohort F) until PD.

The study will be conducted in compliance with the International Council for

Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for

Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.

The initiation of Part 2 will begin when the recommended phase 2 dose (RP2D) is

established in Part 1 in either Cohort A, Cohort B, Cohort E or Cohort F. The cohorts may

begin once the RP2D is determined for each cohort independently during Part 1. All

expansion decisions will be determined by the DEC after review of all safety, PK,

biomarker and preliminary efficacy data, as applicable. During Part 2, the Independent

Expert Reviewer will review safety data and any other data deemed relevant so that

subject safety is ensured.