A Study of Durvalumab in Combination With Lenalidomide With and Without Dexamethasone in Adults With Newly Diagnosed Multiple Myeloma

The dose-finding phase will determine recommended dose (RD) for durvalumab in combination with lenalidomide (LEN) with and without dexamethasone (dex) in a 28-day treatment cycle. Three treatment Cohorts (A, B, and C) will be enrolled in parallel: * Cohort A: durvalumab + LEN + dex in high risk transplant non-eligible (TNE) newly diagnosed multiple myeloma (NDMM) participants; * Cohort B: durvalumab + LEN + dex (dex for up to 12 cycles) in ≥ 65 years old TNE NDMM participants who are not high risk; * Cohort C: durvalumab + LEN as maintenance in post-transplant high risk NDMM participants. Based on experience with durvalumab for other indications, the initial dose of durvalumab will be 1500 mg for each treatment cohort. The dose of durvalumab might be de-escalated to 750 mg level. The dose of LEN will be 25 mg (adjustable per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle for participants in Cohort A and B. The dose of LEN will be 10 mg on Days 1 to 21 of each 28-day treatment cycle for participants in Cohort C. The dose of dex will be 40 mg/day (for participants ≤ 75 years old) or 20 mg/day (for participants \> 75 years old) on Days 1, 8, 15, and 22 of a 28-day cycle for Cohort A and Cohort B (for up to 12 cycles). Initially, 6 participants will be enrolled into each cohort and each will receive 1500 mg durvalumab. The dose-limiting toxicity (DLT) evaluation period will be the first treatment cycle. * If ≤ 1 of the 6 initial participants experience a DLT within the first cycle, then the dose expansion phase may be initiated with durvalumab 1500 mg as the recommended dose (RD); * If 2 or more of the 6 initial participants experience a DLT within the first cycle, then the maximum tolerated dose (MTD) has been exceeded and de-escalation to durvalumab 750 mg level after review of safety and pharmacokinetic/pharmacodynamic (PK/Pd) of the initial 6 participants by the Dose Review Team (DRT). Any of the cohorts may be removed from the study based on emerging PK, Pd, efficacy or safety data. Dose de-escalation will only occur after review of safety (DLT) and possibly PK/Pd data by the Dose Review Team ( DRT). Note: In the US, two treatment arms (A and B) will be enrolled in parallel. Cohort C will enroll upon completion of at least 4 cycles of follow-up for safety assessment of Cohorts A and B.