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

Study Overview
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Brief Summary
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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.

Official Title
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An Open-Label Study of Ciforadenant in Combination With Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Ciforadenant
* Drug: daratumumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ciforadenant in combination with daratumumab<br>Ciforadenant 100 mg orally twice daily in combination with daratumumab IV 16 mg/kg. | Drug: Ciforadenant<br>* 100 mg orally twice daily for 28-day cycles<br>* Other names: CPI-444;Drug: daratumumab<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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