Study of AZD0120 in Newly Diagnosed Multiple Myeloma Ineligible for ASCT

The primary objective is to demonstrate the superiority of IsaVRd or DRd induction followed by a single administration of AZD0120 compared to IsaVRd or DRd induction followed by continuous IsaRd or DRd in terms of progression-free survival (PFS) according to IMWG 2016 criteria, and as assessed by Blinded Independent Central Review (BICR) and miminal residual disease (MRD) negative complete response (CR) rate at 9 months post-randomisation in participants with NDMM who are ineligible to receive ASCT as initial therapy.

Inclusion criteria

• Participants must be 18 years or older, at the time of signing the ICF.
• Participant must have documented diagnosis of MM according to the IMWG diagnostic criteria.
• 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.
• Participant must be deemed ineligible for ASCT while also having adequate organ function for CAR-T cell treatment.
• Participant is a candidate to receive at least one of the regimens (IsaVRd or DRd) as determined by the Investigator.
• ECOG performance status Grade of 0 to 2.
• Participant must have adequate organ and bone marrow function.

Exclusion criteria

• Participant has active or prior CNS or meningeal involvement of MM.
• Participant has primary amyloidosis, active plasma cell leukemia (≥5% circulating plasma cells), Waldenström macroglobulinemia, or POEMS syndrome.
• Participant has significant neurological or psychiatric condition posing risk or impairing evaluation.
• Participant has any other significant medical condition that increases unacceptable risk, interferes with therapy delivery, or confounds evaluation.
• Participant has a history of a prior non-haematologic malignancy unless the participant has been disease-free with no evidence of recurrence for ≥ 2 years.
• Participant has a history of haematologic malignancies, other than MM, regardless of remission status.
• Participant is positive for any of the following:

• HIV: Known to be seropositive for HIV (including any history of HIV).
• Chronic or active hepatitis B.
• Active hepatitis C: Hepatitis C infection.
• Additional local requirements for the testing for infectious diseases and exclusions of applicable participants should be followed per local regulations.
• Participant has clinically significant cardiovascular disease.
• Participant has COPD with an FEV1 < 50% of predicted normal.
• Additional exclusion for participants who are planned to receive IsaVRd as induction: Participant has peripheral neuropathy Grade 4, Grade 3, Grade 2, or Grade 1 with pain.