CT-P44 3.1

Adults with documented measurable RRMM, prior response (PR+) and progression after last line, 1-3 prior lines, ECOG 0-2, protocol-defined organ/blood function, contraception/pregnancy requirements, informed consent.

To be eligible, patients must meet all criteria during Screening and before randomization (Day 1 Cycle 1): 1) Male or female, age >=18 years. 2) Documented MM per IMWG diagnostic criteria and measurable disease at Screening by either: - Serum M-protein >=1.0 g/dL OR urine M-protein >=200 mg/24 h, OR - Light-chain MM with involved serum free light chain >=10 mg/dL and abnormal serum FLC ratio. 3) Relapsed or refractory disease: - Relapsed: progressive disease (PD) after initial response to prior treatment, >60 days after stopping treatment. - Refractory: <25% reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or <=60 days after treatment cessation. 4) Achieved response (PR or better by investigator per IMWG criteria) to at least one prior regimen. - If UPEP response data were unavailable in patients with measurable M-protein during prior therapies, response based on SPEP + serum FLC is acceptable. 5) PD by IMWG criteria on or after the last line of therapy. 6) Received at least 1 but no more than 3 prior MM lines. - A line may include one or more agents and may include induction, HSCT, and maintenance. - Radiotherapy, bisphosphonate, or one short corticosteroid course (<=dexamethasone 40 mg/day for 4 days equivalent) does not count as a prior line. 7) ECOG PS 0, 1, or 2. 8) Required laboratory criteria: a) ANC >=1.0 x 10^9/L without G-CSF/GM-CSF within 14 days before first dose. b) Hemoglobin >=7.5 g/dL without RBC transfusion and erythropoiesis-stimulating agent within 14 days before first dose. c) Platelets >=75 x 10^9/L if bone marrow plasma cells <50%; otherwise >=50 x 10^9/L, without platelet transfusion within 7 days and no thrombopoietin within 14 days before first dose. d) AST and ALT <=2.5 x ULN. e) Alkaline phosphatase <=2.5 x ULN. f) Total bilirubin <=1.5 x ULN (except congenital bilirubinemia such as Gilbert syndrome: total bilirubin <3.0 mg/dL). g) CrCl >=30 mL/min (Cockcroft-Gault acceptable; MDRD/CKD-EPI also acceptable after conversion to mL/min as protocol described). h) Potassium >3.0 mEq/L. i) Corrected calcium <13.5 mg/dL (<3.4 mmol/L) or ionized calcium <7.2 mg/dL (<1.8 mmol/L). 9) Toxicities from prior therapy resolved/stabilized to <=Grade 1 (CTCAE v5.0). 10) Life expectancy >6 months (investigator judgment). 11) Women of childbearing potential: two negative pregnancy tests prior to first dose (serum at 10-14 days before C1D1 and urine before dosing on C1D1). 12) Male and female patients and partners of childbearing potential must use medically acceptable effective contraception per local requirements: - Male: latex/synthetic condom during sexual contact with females of reproductive potential. - Female of reproductive potential: abstain or use two methods (highly effective + additional effective), starting 4 weeks before C1D1 through study and for 5 months after last daratumumab dose. 13) Able to comprehend study nature/purpose and comply with protocol requirements. 14) Signed informed consent before any study-specific procedures (patient and/or legally authorized representative as applicable).

Prior anti-CD38 therapy or lenalidomide-refractory/intolerant disease, recent prohibited anti-myeloma/investigational therapies or transplant timing violations, major comorbid hematologic/plasma-cell disorders, significant uncontrolled medical/infectious/cardiopulmonary conditions, active HBV/HCV/HIV, pregnancy/breastfeeding.

Exclusion applies if any criterion is met during Screening or before randomization (C1D1): 1) Body weight >120 kg. 2) Prior daratumumab or any other CD38-targeting drug. 3) Evidence of refractoriness or intolerance to lenalidomide; if previously treated with lenalidomide-containing regimen, excluded if: a) Discontinued due to lenalidomide-related AEs, or b) Refractory to any lenalidomide dose. 4) Prior/proximate treatment restrictions: a) Approved anti-myeloma agents within 14 days or 5 PK half-lives before randomization (whichever longer), except emergency short corticosteroid course (dexamethasone-equivalent 40 mg/day up to 4 days) before C1D1. b) Investigational product/device within 28 days or 5 half-lives before randomization (whichever longer). c) Radiation therapy within 14 days before randomization (must recover from radiation toxicities). d) Plasmapheresis within 28 days before randomization. e) Live/live-attenuated vaccine, or any COVID-19 vaccine, within 14 days before randomization. 5) ASCT within 12 weeks before randomization, or inadequate immune recovery post-ASCT (investigator judgment). 6) Any prior allogeneic stem cell transplant (regardless of timing). 7) Planned stem cell transplant during Treatment Period. 8) Known meningeal involvement of MM. 9) Plasma cell leukemia (>2.0 x 10^9/L circulating plasma cells), Waldenstrom macroglobulinemia, AL amyloidosis, light-chain deposition disease, POEMS syndrome, smoldering MM, or monoclonal gammopathy-related disease (e.g., MGUS, monoclonal gammopathy of renal/neurological significance). 10) One or more specified medical conditions: a) Other malignancy (except specified in-situ/skin exceptions) within 5 years before first study drug administration. b) Active GI dysfunction impairing tablet swallowing or study treatment absorption (including prior gastric bypass or bowel resection). c) Hereditary fructose intolerance. d) Known COPD with FEV1 <50% predicted (testing required only if known/suspected COPD). e) Moderate/severe persistent asthma within past 2 years, or currently uncontrolled asthma of any classification, or screening FEV1 <50%; controlled intermittent/mild persistent asthma allowed. f) Clinically significant cardiac disease (e.g., MI within 6 months, unstable angina, NYHA class III-IV CHF, clinically significant ECG abnormalities). g) Known/history of HIV infection. h) Current active HBV or HCV infection (per protocol HBV/HCV testing algorithm). i) Active infection requiring systemic therapy within 2 weeks before randomization (resolved severe past infections may be allowed with documentation). j) Major surgery within 4 weeks pre-randomization, incomplete recovery, or planned major surgery during participation/within 2 weeks after last dose (local-anesthesia minor procedures may be allowed; kyphoplasty/vertebroplasty not considered major surgery). k) Serious/uncontrolled medical or psychiatric condition increasing risk or interfering with therapy/interpretation. 11) Known allergy/hypersensitivity/intolerance to monoclonal antibodies, hyaluronidase, human proteins or excipients, dexamethasone, lenalidomide, or sensitivity to mammalian-derived products. 12) Woman breastfeeding or planning breastfeeding while enrolled or within 5 months after last daratumumab dose. 13) Male planning to father a child or donate semen/sperm from 4 weeks before C1D1 through 5 months after last daratumumab dose. 14) Known/suspected inability to comply with protocol, or any condition making participation not in the patient’s best interest or potentially confounding protocol assessments.