A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma

Inclusion Criteria:

For Parts 1 and 2:

1. Has MM defined by the IMWG criteria with evidence of disease progression and:

• In need of additional myeloma therapy as determined by the investigator.

• Has previously received at least 3 lines of myeloma therapy (for example, containingan Immunomodulatory imide drug [IMiD], a proteasome inhibitor [PI], an alkylatingagent, and/or an anti-CD38 as single agents or in combination).

• Is either refractory to or intolerant of at least 1 PI and a least 1 IMiD.

For Part 3:

1. Has MM defined by the IMWG criteria with evidence of disease progression and:

• In need of additional myeloma therapy as determined by the investigator.

• Has previously received at least 3 lines of myeloma therapy.

• Is refractory to at least 1 IMiD (ie, lenalidomide or pomalidomide [thalidomideexcluded]), at least 1 PI (ie, bortezomib, ixazomib, or carfilzomib), andrefractory to at least 1 anti-CD38 antibody (ie, daratumumab or isatuximab) andhas demonstrated disease progression with the last therapy. Participants whoare primary refractory, meaning they never achieved at least a MR with anyprevious treatment line, are not eligible.

2. For participants in Part 2 and 3 only: Measurable disease is defined as :

3. Serum M-protein ≥500 mg/dL (≥5 g/L)

4. Urine M-protein ≥200 mg/24 hours.

5. Serum free light chain (FLC) assay, with involved FLC level ≥10 mg/dL (≥100mg/L) provided serum FLC ratio is abnormal.

6. During Part 1 only, participants not meeting the above criteria for measurabledisease should, at least, have measurable bone marrow plasmacytosis (greater than orequal to [≥ ] 10 percent [%]) and/or plasmacytoma (≥1 centimeter [cm] in diameter)detected by physical examination or imaging.

7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

Exclusion Criteria:

For Parts 1 and 2:

1. Has polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skinchanges (POEMS) syndrome, monoclonal gammopathy of unknown significance, smolderingmyeloma, solitary plasmacytoma, amyloidosis, Waldenstrom macroglobulinemia orimmunoglobulin M (IgM) myeloma, or lymphoplasmacytic lymphoma (LPL).

2. Who have received autologous stem cell transplant (SCT) 60 days before firstinfusion of modakafusp alfa or participants who have received allogeneic SCT 6months before first infusion. Graft-versus-host disease that is active or requiresongoing systemic immunosuppression.

3. Has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE less than or equal to (≤) Grade 1 or baseline, except for sensory or motor neuropathy which should haverecovered to ≤ Grade 2 or baseline.

4. Has clinical signs of central nervous system involvement of MM.

For Part 3:

• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Seropositive forhepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg].Participants with resolved infection (that is, participants who are HBsAg negativebut positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodiesto hepatitis B surface antigen [anti-HBs]) must be screened using real-timepolymerase chain reaction (PCR) measurement of HBV DNA levels. Those who are PCRpositive will be excluded.

• In addition to the above criteria, participants must not have plasma cell leukemiaor have had primary refractory MM, current central nervous system involvement of MM,myelodysplastic syndrome, myeloproliferative syndrome, or have had a secondmalignancy within the previous 3 years, except treated basal cell or localizedsquamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ,resected colorectal adenomatous polyps, breast cancer in situ, or other malignancyfor which the participant is not on active anticancer therapy.