Clinical Trials /

Dose-Escalation Study of BFCR4350A in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)

NCT03275103

Description:

This is a phase I, multicenter, open-label, dose-escalation study of BFCR4350A administered as a single agent by IV infusion to participants with relapsed or refractory multiple myeloma (R/R MM).

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dose-Escalation Study of BFCR4350A in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)
  • Official Title: An Open-Label, Multicenter, Phase I Trial Evaluating the Safety and Pharmacokinetics of Escalating Doses of BFCR4350A in Patients With Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: GO39775
  • NCT ID: NCT03275103

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
BFCR4350ARO7187797Expansion Phase for BFCR4350A

Purpose

This is a phase I, multicenter, open-label, dose-escalation study of BFCR4350A administered as a single agent by IV infusion to participants with relapsed or refractory multiple myeloma (R/R MM).

Trial Arms

NameTypeDescriptionInterventions
Single Step Dose Escalation for BFCR4350AExperimentalStudy drug will be administered intravenously on a 21-day cycle. The step-up dose will be given on Cycle 1 Day 1 and the target dose will be given on C1D8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.
  • BFCR4350A
Multi-Step Dose Escalation for BFCR4350AExperimentalIn Cycle 1, participants will receive 2 step-up doses and a target dose. The step-up dose will be given on Cycle 1 Day 1 and C1D8. The target dose will be given on C1D15. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.
  • BFCR4350A
Expansion Phase for BFCR4350AExperimentalThe expansion stage may consist of a single-step dose escalation arm and/or a multi-step dose escalation arm. The decision regarding which arm(s) to open and how many patients to be enrolled in each arm will be made by the Medical Monitor. The expansion stage of the study may use the dosing and assessment schedule from either the single or multi-step dose escalation arm in Cycle 1.
  • BFCR4350A

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Life expectancy of at least 12 weeks

          -  Participants must have relapsed or refractory (R/R) multiple myeloma (MM) for which no
             established therapy for MM is appropriate and available or be intolerant to those
             established therapies

          -  Adverse events from prior anti-cancer therapy resolved to Grade < or = 1, except any
             grade alopecia and/or peripheral sensory or motor neuropathy which must have resolved
             to Grade < or = 2

          -  Measurable disease defined by laboratory test results

          -  Female participants of childbearing age must agree to remain abstinent or use reliable
             contraceptive methods during the treatment period, and at least 3 months after last
             dose of study drug

          -  Male participants must agree to refrain from donating sperm, to abstain or use a
             condom during the treatment period, and at least 60 days after last dose of study drug

        Exclusion Criteria:

          -  Inability to comply with protocol-mandated hospitalization and activities restrictions

          -  Pregnant, lactating, or planning to become pregnant during the study and up to 3
             months after last dose of study drug

          -  Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate
             within 4 weeks before first infusion

          -  Prior treatment with systemic immunotherapeutic agents within 12 weeks or 5 half-lives
             of the drug, whichever is shorter, before first infusion

          -  Treatment-related, immune-mediated adverse events associated with prior
             immunotherapeutic agents

          -  Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other
             anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the
             drug, whichever is shorter, prior to first BFCR4350A infusion

          -  Autologous stem cell transplantation (SCT) within 100 days prior to first infusion

          -  Prior allogeneic SCT or solid organ transplantation

          -  Primary or secondary plasma cell leukemia

          -  History of autoimmune disease or of confirmed progressive multifocal
             leukoencephalopathy

          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
             (or recombinant antibody-related fusion proteins)

          -  Patients with known history of amyloidosis (e.g., positive Congo Red stain or
             equivalent in tissue biopsy)

          -  Patients with lesions in proximity of vital organs that may develop sudden
             decompensation/deterioration in the setting of a tumor flare

          -  History of other malignancy that could affect compliance with the protocol or
             interpretation of results

          -  Current or past history of central nervous system (CNS) disease, or CNS involvement by
             MM

          -  Significant cardiovascular disease or active pulmonary disease that may limit a
             patient's ability to adequately respond to a CRS event

          -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
             (excluding fungal infections of nail beds) at study enrollment, or any major episode
             of infection requiring treatment with IV antibiotics within 4 weeks prior to first
             infusion

          -  Known or suspected chronic active Epstein-Barr virus (EBV) infection, acute or chronic
             hepatitis C virus (HCV) infection

          -  Positive serologic or polymerase chain reaction (PCR) test results for acute or
             chronic hepatitis B virus (HBV) infection

          -  Recent major surgery within 4 weeks prior to first infusion

          -  Human Immunodeficiency Virus (HIV) positive

          -  History of illicit drug or alcohol abuse within 12 months prior to screening

          -  Any medical condition or laboratory test abnormality that precludes the participant's
             safe participation in and completion of the study, or which could affect compliance
             with the protocol or interpretation of results
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and Severity of Adverse Events (AEs)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.

Secondary Outcome Measures

Measure:Cmax
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Defined as the maximum observed serum concentration of study drug.
Measure:Objective Response Rate (ORR)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:OR is defined as percentage of participants with partial response (PR) or complete response (CR). CR is defined as no evidence of initial monoclonal protein isotype(s) on immunofixation of the serum and urine, disappearance of any soft tissue plasmacytomas, and </= 5% plasma cells in bone marrow (BM). PR is defined as >/= 50% reduction of serum M-protein and reduction in 24-hour urine M-protein by >/= 90% or to < 200 milligrams (mg)/24 hours.
Measure:Duration of Response
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Time from first occurrence of OR (defined previously) to disease progression (PD) or death from any cause. PD: increase of >/=25% from lowest response value in one of the following: serum M-protein (absolute increase >/=0.5 grams per deciliter (g/dL); serum M-protein increase >/=1g/dL, if lowest M component was >/=5g/dL; urine M-protein (absolute increase >/=200 mg/24 hours); no measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase >10 mg/dL); no measurable serum and urine M-protein levels and no measurable disease by FLC: BM plasma cell % irrespective of baseline status (absolute % >/=10%); new lesion(s) >/=50% increase from lowest point in sum of the products of diameters of > 1 lesion, or >/=50% increase in longest diameter of a previous lesion >1 centimeter (cm) in short axis; >/=50% increase in circulating plasma cells (minimum 200 cells per microliter) if only measure of disease.
Measure:Change from Baseline in the Presence Anti-Drug Antibodies (ADAs)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:To evaluate the immune response to the study drug.
Measure:Minimum observed serum concentration (Cmin)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Defined as the minimum observed serum concentration of study drug.
Measure:Area Under the Concentration-Time Curve
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Defined as the total exposure of study drug.
Measure:Clearance (CL)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Defined as the volume of plasma cleared of the drug per unit time.
Measure:Volume of Distribution at Steady State (Vdss)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genentech, Inc.

Last Updated

January 31, 2020