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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03275103
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : August 26, 2019
Information provided by (Responsible Party):
Genentech, Inc.

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: BFCR4350A Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 19, 2017
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Dose Escalation for BFCR4350A
Study drug will be administered intravenously on a 21-day cycle. Initially, cohorts will consist of 1 participant each. Subsequently will consist of at least 3 participants, unless dose-limiting toxicities (DLTs) are observed in the first 2 prior to enrollment of a third participant. For each cohort, treatment with the first dose will be staggered such that the second participant enrolled in the cohort will receive study drug at least 72 hours after the first participant receives it to allow assessment of any severe and unexpected acute or subacute drug or infusion-related toxicities; dosing in subsequent participants in each cohort will be staggered by at least 24 hours.
Drug: BFCR4350A
BFCR4350A will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: RO7187797

Experimental: Expansion Phase for BFCR4350A
Participants exhibiting acceptable safety and evidence of clinical benefit will be administered study drug every 21 days up to a maximum of 17 cycles until objective disease progression is documented or unacceptable toxicity, whichever occurs first.
Drug: BFCR4350A
BFCR4350A will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: RO7187797

Primary Outcome Measures :
  1. Incidence and Severity of Adverse Events (AEs) [ Time Frame: Up to approximately 3 years ]
    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 :
  1. Cmax [ Time Frame: Up to approximately 3 years ]
    Defined as the maximum observed serum concentration of study drug.

  2. Objective Response Rate (ORR) [ Time Frame: Up to approximately 3 years ]

    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.

  3. Duration of Response [ Time Frame: Up to approximately 3 years ]
    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.

  4. Change from Baseline in the Presence Anti-Drug Antibodies (ADAs) [ Time Frame: Up to approximately 3 years ]
    To evaluate the immune response to the study drug.

  5. Minimum observed serum concentration (Cmin) [ Time Frame: Up to approximately 3 years ]
    Defined as the minimum observed serum concentration of study drug.

  6. Area Under the Concentration-Time Curve [ Time Frame: Up to approximately 3 years ]
    Defined as the total exposure of study drug.

  7. Clearance (CL) [ Time Frame: Up to approximately 3 years ]
    Defined as the volume of plasma cleared of the drug per unit time.

  8. Volume of Distribution at Steady State (Vdss) [ Time Frame: Up to approximately 3 years ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03275103

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Contact: Reference Study ID Number: GO39775 888-662-6728 (U.S. only)

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United States, Arizona
Mayo Clinic Hospital - Arizona Recruiting
Scottsdale, Arizona, United States, 85259
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
United States, Colorado
University of Colorado Denver Recruiting
Aurora, Colorado, United States, 80045
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Australia, Victoria
Peter MacCallum Cancer Center Recruiting
Melbourne, Victoria, Australia, 3000
Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Canada, Ontario
Princess Margaret Cancer Center Recruiting
Toronto, Ontario, Canada, M5G 1Z5
Sponsors and Collaborators
Genentech, Inc.
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Study Director: Clinical Trials Genentech, Inc.

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Responsible Party: Genentech, Inc. Identifier: NCT03275103     History of Changes
Other Study ID Numbers: GO39775
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases