Study of Melphalan Flufenamide (Melflufen) + Dex With Bortezomib or Daratumumab in Patients With RRMM

Inclusion Criteria: 1. Male or female, age 18 years or older 2. A prior diagnosis of multiple myeloma with documented disease progression in need of treatment at time of screening 3. One to four prior lines of therapy 4. Measurable disease defined as any of the following: * Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP) * ≥ 200 mg/24 hours of monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP) * Serum free light chain (SFLC) ≥ 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio 5. Life expectancy of ≥ 6 months 6. ECOG performance status ≤ 2. (Patients with lower performance status based solely on bone pain secondary to multiple myeloma may be eligible following consultation and approval of the medical monitor) 7. Patient is a female of childbearing potential (FCBP)\* with a negative serum or urine pregnancy test prior to initiation of therapy and agrees to practice appropriate methods of birth control, or the patient is male and agrees to practice appropriate methods of birth control 8. Ability to understand the purpose and risks of the study and provide signed and dated informed consent 9. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec 10. Adequate organ function with the following laboratory results during screening (within 21 days) and immediately before study drug administration on Cycle 1 Day 1: * Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (1.0 x 109/L) (Growth factors cannot be used within 10 days (14 days for pegfilgrastim) prior to initiation of therapy) * Platelet count ≥ 75,000 cells/mm3 (75 x 109/L) (without required transfusions during the 10 days prior to initiation of therapy) * Hemoglobin ≥ 8.0 g/dl (red blood cell (RBC) transfusions are permitted) * Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), or patients diagnosed with Gilbert's syndrome, that have been reviewed and approved by the medical monitor * AST/SGOT and ALT/SGPT ≤ 3.0 x ULN * Renal function: Estimated creatinine clearance by Cockcroft-Gault formula ≥ 45 mL/min and serum creatinine ≤ 2 mg/dL 11. Must have, or be willing to have an acceptable central catheter. (Port a cath, peripherally inserted central catheter \[PICC\] line, or central venous catheter) Regimen A 12. Must be intolerant or refractory to a prior IMiD; refractory defined as failure to respond (MR or better) or progression while on therapy or within 60 days of last dose. Regimen B 13. Must have had a prior IMiD and a proteasome inhibitor (PI); alone or in combination and must be refractory or intolerant to an IMiD, PI or both. * (FCBP) is any sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (not having menstrual cycles due to cancer therapy does not rule out childbearing potential) for at least 24 consecutive months. Exclusion Criteria: 1. Primary refractory disease (i.e. never responded with ≥ MR to any prior therapy) 2. Evidence of mucosal or internal bleeding and/or are platelet transfusion refractory (i.e. platelet count fails to increase by \> 10,000 cells/mm3 after transfusion of an appropriate dose of platelets) 3. Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study. Examples of such conditions are: a significant history of cardiovascular disease (e.g., myocardial infarction, significant conduction system abnormalities, uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months) 4. Known active infection requiring parenteral or oral anti-infective treatment within 14 days of initiation of therapy 5. Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance 6. Pregnant or breast-feeding females 7. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation 8. Known human immunodeficiency virus or active hepatitis B or C viral infection 9. Concurrent symptomatic amyloidosis or plasma cell leukemia 10. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) 11. Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 3 weeks (6 weeks for nitrosoureas) prior to initiation of therapy. The use of live vaccines within 30 days before initiation of therapy. IMiDs, PIs and or corticosteroids within 2 weeks prior to initiation of therapy. Other investigational therapies and monoclonal antibodies (mAb) within 4 weeks of initiation of therapy Prednisone up to but no more than 10 mg orally once daily (q.d.) or its equivalent for symptom management of comorbid conditions is permitted but dose should be stable for at least 7 days prior to initiation of therapy 12. Residual side effects to previous therapy \> Grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy Grade 1 without pain are permitted) 13. Prior peripheral stem cell transplant within 12 weeks of initiation of therapy 14. Prior allogeneic stem cell transplantation with active graft-versus-host- disease 15. Prior major surgical procedure or radiation therapy within 4 weeks of initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy) 16. Known intolerance to the required dose and schedule of steroid therapy as determined by the investigator 17. Prior treatment with melflufen Regimen A 18. Refractory to a PI in the last line of therapy prior to enrollment in this trial; refractory defined as failure to respond (MR or better) or progression while on therapy or within 60 days of last dose 19. History of allergic reaction/hypersensitivity attributed to compounds containing boron, mannitol, polysorbate 80 or sodium citrate dihydrate Regimen B 20. Prior exposure to an antiCD-38 mAb 21. Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) less than 50% of predicted normal 22. Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification 23. ≥ Grade 3 conduction system abnormalities unless patient has a pacemaker 24. Active hepatitis B (defined as HBsAg+) or those at risk for reactivation (HBsAg-, Anti- HBs+, Anti-HBc+) * Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-, Anti-HBs+, Anti-HBc-) * Non-active hepatitis B (HBsAg-, Anti-HBs+, Anti-HBc+) may only be enrolled after approval of the sponsor and consideration of risk of reactivation (additional screening and monitoring for reactivation of Hepatitis B and consultation with a liver disease specialist may be required)