A Study of Modakafusp Alfa Together With Daratumumab Adults With Relapsed or Refractory Multiple Myeloma

Inclusion Criteria:

1. Documented multiple myeloma (MM) diagnosis per IMWG criteria.
2. Measurable disease, defined as at least 1 of the following:

   1. Serum M protein ≥0.5 grams per deciliter \[g/dL\] (≥5 g/L) on serum protein electrophoresis (SPEP).
   2. Urine M protein ≥200 mg/24 hours on urine protein electrophoresis (UPEP).
   3. Serum free light chain (FLC) assay with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.
3. 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.
4. For participants in Phase 2a Dose Finding only:

   1. Received 1 to 3 prior line(s) of antimyeloma therapy.
   2. Must be refractory to prior lenalidomide treatment.
   3. Participants must be sensitive (nonrefractory) or naïve to prior anti-CD38 mAb treatment.
   4. Documented progressive disease on or after the last regimen.
   5. Participants must have PR or better to at least 1 line of prior therapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening.

Exclusion Criteria:

1. Prior exposure to modakafusp alfa.
2. Participant has polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, plasma cell leukemia, or lymphoplasmacytic lymphoma.
3. 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.
4. Previous allogeneic stem cell transplant at any time or autologous stem cell transplant (ASCT) within 12 weeks of planned start of dosing.
5. Seropositive for hepatitis B, or known history of seropositivity for hepatitis C or of seropositivity for human immunodeficiency virus (HIV).
6. 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.
7. Participant has QT interval corrected by the Fridericia method \>480 milliseconds \[msec\] (Grade ≥2).
8. 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).