PK of Melphalan During Treatment With Melflufen and Dexamethasone in Patients With RRMM and Impaired Renal Function

Inclusion Criteria

• •1. Male or female, age 18 years or older, at the time of signing the informed consent;
• •2. A prior diagnosis of multiple myeloma (MM) with documented disease progression in need of treatment at time of screening;
• •3. Received at least 2 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. Eastern Cooperative Oncology Group (ECOG) performance status ≤2. (Patients with lower performance status based solely on bone pain secondary to MM 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. Renal function: Estimated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula on 2 consecutive screening evaluations. Patients meeting criteria for Screening 1, must also meet criteria for Screening 2 following optimal hydration (as determined by the investigator). Screening 2 must be on or as close as possible to treatment start date (preferably \<24-48 hours) but cannot exceed 72 hours.
• •• Cohort 1 (a and b): Screening 1: eGFR between ≥25 mL/min/1.73m² to \<45 mL/min/1.73m². Screening 2: eGFR between ≥30 mL/min/1.73m² to \<45 mL/min/1.73m².
• •• Cohort 2 (a and b): Screening 1: eGFR between ≥10 mL/min/1.73m² to \<35 mL/min/1.73m². Screening 2: eGFR between ≥15 mL/min/1.73m² to \<30 mL/min/1.73m².
• •Cohort 2b will only be enrolled following approval of Data Safety Monitoring Committee (DSMC) after evaluating data from Cohort 1a, 1b and 2a.
• •Patients with fluctuating values of eGFR may be eligible following consideration of additional assessments in consultation with the medical monitor.
• •11. The following laboratory results must be met 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 higher in patients diagnosed with Gilbert's syndrome, that have been reviewed and approved by the medical monitor
• •* Aspartate transaminase / serum glutamic oxaloacetic transaminase (AST / SGOT) and alanine transaminase / serum glutamic pyruvic transaminase (ALT / SGPT) ≤3.0 x ULN;
• •12. Must have, or be willing to have, an acceptable central catheter. (Port a cath, peripherally inserted central catheter \[PICC\] line, or central venous catheter).
• •Footnote
• •\*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.