The following criteria is provided for health care professionals.

Inclusion Criteria:

• Documented multiple myeloma (MM) diagnosis per IMWG criteria.
• Measurable disease, defined as at least 1 of the following:
  • Serum M protein ≥0.5 grams per deciliter [g/dL] (≥5 g/L) on serum protein electrophoresis (SPEP).
  • Urine M protein ≥200 mg/24 hours on urine protein electrophoresis (UPEP).
  • Serum free light chain (FLC) assay with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.
• For participants in the Phase 1 Dose Escalation only:
  • Must have received at least 3 prior lines of therapy, including at least 1 proteosome inhibitor (PI), 1 immunomodulatory imide drug (IMiD), and 1 anti-CD38 monoclonal antibody (mAb) drug; or who are triple refractory to a PI, an IMiD, and an anti-CD38 mAb drug, regardless of the number of prior line(s) or therapy.
• For participants in Phase 2a Dose Finding only:
• • Received 1 to 3 prior line(s) of antimyeloma therapy.
  • Must be refractory to prior lenalidomide treatment.
  • Participants must be sensitive (nonrefractory) or naïve to prior anti-CD38 mAb treatment.
  • Documented progressive disease on or after the last regimen.
  • Participants must have PR or better to at least 1 line of prior therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening.

Exclusion Criteria:

• Prior exposure to modakafusp alfa.
• Participant has polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, plasma cell leukemia, or lymphoplasmacytic lymphoma.
• Participant has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE, Version 5 Grade ≤1 or baseline, except for alopecia.
• Previous allogeneic stem cell transplant at any time or autologous stem cell transplant (ASCT) within 12 weeks of planned start of dosing.
• Seropositive for hepatitis B, or known history of seropositivity for hepatitis C or of seropositivity for human immunodeficiency virus (HIV).
• Participant has congestive heart failure (New York Heart Association Grade ≥II), cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant arrhythmia requiring therapy including anticoagulants, or clinically significant uncontrolled hypertension.
• Participant has QT interval corrected by the Fridericia method >480 milliseconds [msec] (Grade ≥2).
• Participant has a chronic condition that will require the chronic use of systemic corticosteroids >10 milligrams per day (mg/d) of prednisone or equivalent on top of any required corticosteroids for multiple myeloma (MM).