Study to Separately Evaluate the Activity of Talacotuzumab (JNJ-56022473) or Daratumumab in Transfusion-Dependent Participants With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) Who Are Relapsed or Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment

This is a multicenter, randomized (study drug assigned by chance), open-label (participants
and researchers are aware of the treatment participants are receiving) study to evaluate the
safety and efficacy of talacotuzumab or daratumumab. Approximately 60 participants (30 to
receive talacotuzumab and 30 to receive daratumumab) will be enrolled and then assigned
randomly on a 1:1 basis to receive either talacotuzumab or daratumumab. The study consists
of: a Screening Phase of up to 28 days during which participant eligibility will be reviewed
and approved by the sponsor prior to randomization, a Treatment Phase that will extend from
the first dose on Cycle 1 Day 1 until study drug discontinuation, and a Post-treatment Follow
up Phase beginning once the participant discontinues talacotuzumab or daratumumab. Study
drugs will continue to be administered until disease progression, lack of response,
unacceptable toxicity, withdrawal of consent, or study end. Safety will be monitored
throughout the study. The talacotuzumab arm of the study is closed for enrollment.

Inclusion Criteria:

- Myelodysplastic Syndrome (MDS) according to World Health Organization (WHO) criteria
confirmed by bone marrow aspirate and biopsy within 12 weeks prior to first dose. A
local laboratory report from this diagnostic bone marrow aspirate and biopsy must be
approved by the sponsor

- International Prognostic Scoring System (IPSS) low risk or intermediate-1 risk MDS

- Red blood cell (RBC) transfusion dependent, 1) Received at least 4 units of RBCs over
any 8 consecutive weeks during the 16 weeks prior to randomization, 2) Pretransfusion
Hb must have been less than or equal to (<=)9.0 gram per deciliter (g/dL)

- Adequate iron stores, defined as transferrin saturation greater than 20 percent (%)
and serum ferritin greater than 400 nanogram per Milliliter (ng/mL), measured within
the screening period, or adequate iron stores as demonstrated by recent (within 12
weeks prior to first dose) bone marrow examination with iron stain

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

- Known allergies, hypersensitivity, or intolerance to talacotuzumab and daratumumab or
their excipients

- Received any chemotherapy, immunomodulatory or immunosuppressive therapy,
corticosteroids (greater than [>]30 milligram per day [mg/day] prednisone or
equivalent) within 28 days prior to randomization

- Received other treatments for MDS within 28 days prior to first dose (example [eg],
azacitidine, decitabine, lenalidomide, Erythropoiesis-Stimulating Agent (ESA) (8 weeks
for long-acting ESAs)

- History of hematopoietic stem cell transplant

- Del(5q) karyotype unless treatment with lenalidomide has failed. Failure is defined as
either: 1) having received at least 3 months of lenalidomide treatment without RBC
transfusion benefit (International Working Group [IWG] 2006); 2) progression or
relapse after hematologic improvement with lenalidomide (IWG 2006); 3) discontinuation
of lenalidomide due to toxicity; or 4) unable to receive lenalidomide due to a
contraindication. Source documentation for lenalidomide treatment failure must be
verified by the sponsor