A Study to Determine the Efficacy of the Combination of Daratumumab (DARA) Plus Durvalumab (DURVA) (D2) in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)

Indication: This study will include subjects that have relapsed and refractory multiple myeloma (RRMM) after treatment with at least 3 prior antimyeloma therapies, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD®) or after development of double-refractoriness to a both a PI and an IMiD. The most recent multiple myeloma (MM) treatment regimen should contain daratumumab (DARA) and subjects must have progressed on DARA while on this regimen. Stage 1 A cohort of 18 subjects will be enrolled to determine the preliminary efficacy of DARA plus DURVA. Once the 18 subjects have been enrolled, an interim analysis for futility purpose will be conducted to determine if the study can proceed to Stage 2. Early Safety Monitoring Once 6 subjects have been enrolled and completed the first treatment cycle in Stage 1 of this study, the enrollment continuity would depend on the availability of safety data from the on-going Phase 2 study (MEDI4736-MM-003) of DARA and DURVA in previously DARA-naïve patients. * If MEDI4736-MM-003 safety data are available and the tolerability profile of DARA plus DURVA has been determined to be adequate, then enrollment will continue as planned in Stage 1 without an early safety monitoring review of the data. * If safety data are not available enrollment in this study will be paused for a review of the safety profile of DARA plus DURVA by a Dose Review Team (DRT), using the data from the first 6 patients. * If ≥ 1 of the first 6 patients experiences a dose-limiting toxicity (DLT), the study will be halted for review and a change in the dosing regimen may be implemented. * The DRT will consist of the Celgene Medical Monitor, Celgene lead Safety Physician, Celgene biostatistician, other Celgene functional area representatives, as appropriate, study specific consultants (MD/PhD), and site investigator and/or designees who have enrolled subjects to the study. * All available safety and, if applicable, PK/(pharmacodynamic) Pd, biomarker, and preliminary efficacy data will be reviewed and can be considered in the DRT's decisions. * A DRT meeting will be held to review all data and make decisions regarding continuity of the study. Dose-limiting Toxicity Dose-limiting toxicities (DLTs) may be evaluated during the DLT evaluation period for the initial 6 patients in Part 1 of the study. The DLT evaluation period will be defined as the first treatment cycle. Subjects are considered evaluable for assessment of DLT if they: * Receive at least 1 dose of study treatments and experience a DLT OR * Receive 1 dose of DURVA, 4 doses of DARA and complete the safety follow-up through the end of the DLT evaluation period. Grading of DLTs will be according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT will be defined as below: Hematologic DLT 1. Grade 4 neutropenia observed for greater than 5 days duration 2. Grade 3 neutropenia associated with fever (≥ 38.5 °C) of any duration. 3. Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement for platelets transfusion. 4. Any other Grade 4 hematologic toxicity that does not resolve to subject's pretreatment baseline level within 72 hours 5. Grade 4 anemia, unexplained by underlying disease. Non-hematologic DLT a. Any nonhematological toxicity ≥ Grade 3 except for alopecia and nausea controlled by medical management b. Any treatment interruption greater than 2 weeks due to an AE. While the rules for adjudicating DLTs in the context of dose escalation are specified above, an AE not listed above may be defined as a DLT after consultation with the Sponsor and investigators, based on the emerging safety profile. Stage 2 If 3 or more subjects achieved a response (PR or better) out of the 18 subjects at the end of Stage 1, an additional 32 subjects will be enrolled to evaluate the safety and efficacy of DARA plus DURVA. Part 2: Expansion Upon completion of Part 1, if at least 9 subjects achieve a response (PR or better) out of a total of 50 subjects and it is determined to further confirm the efficacy and safety of DARA plus DURVA, an additional 70 subjects may be enrolled. An Independent Response Adjudication Committee (IRAC) will be set up for this trial to review study data. The IRAC will determine tumor response to therapy and to confirm the time of disease progression (PD) (if disease progressed) at scheduled or unscheduled visits for each subject. The safety and efficacy of the study will be monitored by an independent Data Monitoring Committee (DMC) who are not involved in the trial conduct. The DMC will meet up and review study data at pre specified intervals throughout the trial. In the event that the trial is halted for early safety monitoring, evaluation of the emerging safety data from the initial 6 patients enrolled in Part 1 will be performed by the Dose Review Team (DRT). Safety data will be monitored by the Celgene Medical Monitor and Safety Physician on an ongoing basis throughout the study. Should a significant safety issue be identified, the DMC will be convened to make a recommendation as to the future conduct of the study. The decision to discontinue a subject, which will not be delayed or refused by the Sponsor, remains the responsibility of the treating physician. However, prior to discontinuing a subject, the Investigator may contact the Medical Monitor and forward appropriate supporting documents for review and discussion. The study will be conducted in compliance with the International Council on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.