A trial to learn how well AZD0120 works and how safe it is in people with relapsed or refractory multiple myeloma.

Prior treatment

• Arm A and B: Participant has active or prior CNS or meningeal involvement of MM.
• Arm A and B: Participant has primary refractory MM (no minimal response to any prior therapy).
• Arm A and B: Participant previously received any BCMA-targeted treatment.
• Arm A and B: Participant previously received CAR-T or CAR-NK therapy.
• Arm A and B: Participant previously received T-cell engager therapy.
• Arm A and B: Participant previously received allogeneic stem cell transplant at any time or ASCT within 12 weeks before randomization.

Other illness

• Arm A and B: Participant has primary amyloidosis, active plasma cell leukemia (≥5% circulating plasma cells), Waldenström macroglobulinemia, or POEMS syndrome.
• Arm A and B: Participant has significant neurological or psychiatric condition posing risk or impairing evaluation (e.g., severe brain injury, dementia, Parkinson’s, stroke, intracranial hemorrhage, or seizure within 6 months). Stable mild conditions may be eligible at Investigator discretion.
• Arm A and B: Participant has any other significant medical condition that increases unacceptable risk, interferes with therapy delivery, or confounds evaluation, including: -Serious active or uncontrolled infection, -Requirement of supplemental oxygen, -Active autoimmune disease or history within 2 years, -Clinically significant gastrointestinal disease (including IBD requiring treatment within 5 years).

• Arm A and B: Participants must be 18 years or older, at the time of signing the ICF.
• Arm A and B: Participant must have documented diagnosis of MM according to the IMWG diagnostic criteria.
• Arm A and B: Participant must have one or more of the following measurable disease criteria: (a) Serum M-protein level ≥1.0 g/dL, (b) Urine M-protein level ≥ 200 mg/24 h, (c) Serum immunoglobulin FLC ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda FLC ratio.
• Arm A and B: Participant must have documented evidence of PD by IMWG 2016 criteria based on Investigator’s determination during or after the most recent line of therapy. Participants who have had only 1 prior line of therapy must have disease that has progressed within 47 months of a stem cell transplant, or if not transplanted, then within 42 months of starting initial therapy.
• Arm A and B: Participant must have received 1 to 3 lines of prior therapy including an IMiD and either a PI or an anti-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.
• Arm A and B: Participant is eligible to receive at least one of the standard regimens (DKd, PVd, DPd, or Kd) as determined by the Investigator.
• Arm A and B: Participants must have an ECOG performance status score of 0 to 1.
• Arm A and B: Adequate organ and bone marrow function.