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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Ciforadenant; Drug: daratumumab

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Corvus Pharmaceuticals, Inc.
• Investigators: Study Director: Deborah Strahs, Corvus Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2020
• Primary Completion (Actual): September 21, 2021
• Study Completion (Actual): March 1, 2022

Study Registration Dates

• First Submitted: February 19, 2020
• First Submitted That Met QC Criteria: February 19, 2020
• First Posted (Actual): February 21, 2020

Study Record Updates

• Last Update Posted (Actual): March 11, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: CPI-444-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No