Study of Ciforadenant in Combination With Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma

• Ciforadenant (Drug), also known as CPI-444: 100 mg orally twice daily for 28-day cycles
• daratumumab (Drug): 16 mg/kg administered intravenously as follows based on 28-day cycles: * Cycles 1 - 2: Days 1, 8, 15, and 22 * Cycles 3 - 6: Days 1 and 15 * Cycles 7 - 24: Day 1

Primary outcomes

• Safety and tolerability of ciforadenant in combination with daratumumab relapsed / refractory multiple myeloma. [From start of treatment to end of treatment, up to 24 months]: Incidence of treatment-emergent adverse events, as assessed by NCI CTCAE v.5
• Safety and tolerability of ciforadenant in combination with daratumumab relapsed / refractory multiple myeloma. [28 days following first administration of ciforadnenat in combination with daratumumab]: Incidence of dose-limiting toxicities (DLTs) of CPI-444 in combination with daratumumab

Secondary outcomes

• Overall response rate. [From start of treatment to end of treatment, up to 24 months]: According to international myeloma working group guidelines (including stringent complete response \[sCR\], complete response \[CR\], very good partial response \[VGPR\], partial response \[PR\]).
• Duration of response. [From start of treatment to end of treatment, up to 24 months]: Time from the first assessment showing objective response to the date of documented disease progression.
• Disease control rate. [From start of treatment to end of treatment, up to 24 months]: Proportion of participants achieving disease control for ≥ 3 months.
• Time to next therapy. [Up to 2 years after end of treatment.]: Time from end of treatment to starting next anti-myeloma therapy.
• Progression free survival. [Up to 2 years after end of treatment.]: Proportion of participants remaining progression free or surviving at a given time.
• Minimal Residual Disease. [From start of treatment to end of treatment, up to 24 months]: Rate of molecular minimal residual disease (MRD) negativity.

Sex: All, ages: 18 Years to 80 Years

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.

• Deborah Strahs, Study director, Corvus Pharmaceuticals