This is a Phase 1b open-label study of ciforadenant, an oral, small molecule inhibitor targeting adenosine-2A receptors (A2AR), on safety/tolerability and efficacy in combination with daratumumab, a monoclonal antibody targeting CD38, in relapsed or refractory multiple myeloma.

Inclusion Criteria:

• Relapsed or refractory myeloma.
• Must have been exposed to at least 2 cycles of an IMiD containing regimen and PI containing regimen and must be refractory to at least one of the two.
• Must have completed and tolerated 2 cycles of daratumumab or other anti-CD38 targeting antibodies.
• Active myeloma requiring systemic treatment.
• Measurable disease per protocol.
• ECOG performance status of 0 - 2.
• Life expectancy of at least 3 months.

Exclusion Criteria:

• POEMS syndrome; non-secretory myeloma (no measurable protein on sFLC assay); amyloidosis.
• History of select prior malignancies.
• Previous intolerance to daratumumab or any study drug.
• Received an allogeneic stem cell transplant within 12 months, or an autologous stem cell transplant within 6 months, or have ongoing toxicity related to transplant.
• Have an active infection or serious comorbid medical condition.
• Any live attenuated vaccination against infectious diseases (e.g., influenza, varicella) within 4 weeks of initiation of study treatment; uncontrolled human immunodeficiency virus, or positive tests for hepatitis B or hepatitis C.
• Female participants pregnant or breast-feeding.
• Screening chemistry and blood counts within protocol limits
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment.