A Study Comparing AZD0120, a Dual-targeted CAR-T Against B-cell Maturation Antigen (BCMA) and CD19, Versus Standard Regimens in Participants With Relapsed Refractory Multiple Myeloma (DURGA-4)

Summary

This is a randomised, multicentre, controlled, open-label, Phase III global study comparing the efficacy and safety of AZD0120 versus standard regimens (DKd \[daratumumab, carfilzomib, and dexamethasone\], DPd \[daratumumab, pomalidomide, and dexamethasone\], PVd \[pomalidomide, bortezomib and dexamethasone\], or Kd \[carfilzomib and dexamethasone\]) in participants with RRMM.

Eligibility

Inclusion Criteria:

* Age ≥ 18 years
* Documented diagnosis of multiple myeloma according to the IMWG diagnostic criteria
* Documented evidence of measurable disease:

  1. Serum M-protein level ≥ 1 g/dL
  2. Urine M-protein level ≥ 200 mg/24h
  3. Serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio
* Documented evidence of PD by IMWG 2016 criteria based on investigator's determination during or after the most recent line of therapy. Participants with only 1 prior line of therapy must have progressed within 47 months of a stem cell transplant, or if not transplanted, then within 42 months of starting initial therapy
* Received 1 to 3 lines of prior therapy including an IMiD and either a PI or a CD38 antibody. Participant must have undergone at least 2 complete cycles of treatment for each line of therapy, unless PD was the best response to the line of therapy
* Eligible to receive at least one of the standard regimens (DKd, PVd, DPd, or Kd) as determined by the Investigator.
* ECOG performance status score of 0 to 1
* Adequate hematology and chemistry laboratory values:

  1. Haemoglobin ≥ 8.0 g/dL
  2. Absolute neutrophil count ≥ 1 × 10\^9/L (1000 per mm3)
  3. Platelet count ≥ 75 × 10\^9/L (75000 per mm3) in participants with \< 50% of bone marrow nucleated cells are plasma cells or ≥ 50 × 10\^9/L (50000 per mm3) in participants with ≥ 50% of bone marrow nucleated cells are plasma cells
  4. Absolute lymphocyte count ≥ 300/µL (0.3 × 109/L)
  5. Total bilirubin ≤ 1.5 × ULN in the absence of Gilbert's syndrome or ≤ 3 × ULN if the participant has Gilbert's syndrome. AST and ALT≤ 3.0 × ULN. CrCl by Cockcroft and Gault method ≥ 30 mL/minute

Exclusion Criteria:

* Known active, or prior history of CNS involvement or exhibits clinical signs of meningeal involvement of MM.
* Primary amyloidosis, active plasma cell leukaemia, Waldenstrom macroglobulinemia or Polyneuropathy Organomegaly Endocrinopathy M-protein and Skin (POEMS) syndrome.
* Participants with primary refractory MM (failed to generate at least a minimal response to any prior therapy)
* Significant neurological or psychiatric condition
* Significant medical condition that places the participant at an unacceptable risk for treatment-related complications
* Previously received any prior BCMA-targeted treatment
* Previously received CAR-T or CAR-NK therapy directed at any target
* Previously received T-cell engager therapy directed at any target
* Previously received allogeneic stem cell transplantation at any time during prior therapy or received autologous stem cell transplantation within 12 weeks of randomization

Conditions2

Interventions6

Locations41 sites

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