Dose-Escalation Study of BFCR4350A in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)
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).
Condition
- Multiple Myeloma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- 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 as anti-cancer therapy 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 - Prior treatment with chimeric antigen receptor (CAR) T-cell therapy within 12 weeks before first BFCR4350A infusion - Known 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 - Absolute plasma cell count exceeding 500/micro L or 5% of the peripheral blood white cells - 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 that may limit a patient's ability to adequately respond to a CRS event - Symptomatic active pulmonary disease requiring supplemental oxygen - Within 14 days prior to first BFCR4350A infusion: 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
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental Arm A: Single Step Dose Escalation for BFCR4350A |
Study 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. |
|
Experimental Arm B: Multistep Dose Escalation for BFCR4350A |
In 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. |
|
Experimental Arm C: Single Step Dose Expansion for BFCR4350A |
The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A. |
|
Experimental Arm D: Multistep Dose Expansion for BFCR4350A |
The multistep dose expansion stage of the study may use the dosing and assessment schedule from the multistep dose escalation arm in Cycle 1, based on data from Arm B. |
|
Experimental Arm E: Expansion Phase for Tocilizumab Pretreatment |
All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of BFCR4350A and Cycle 1 BFCR4350A doses for other treatment arms. |
|
Experimental Arm F: Single Step Dose Expansion for BFCR4350A |
The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A. |
|
Experimental Arm G: Multistep Dose Expansion for BFCR4350A |
The multistep dose expansion stage of the study may use the dosing and assessment schedule from the multistep dose escalation arm in Cycle 1, based on data from Arm B. |
|
Recruiting Locations
University of Alabama at Birmingham
Birmingham, Alabama 35249
Birmingham, Alabama 35249
More Details
- Status
- Recruiting
- Sponsor
- Genentech, Inc.
Study Contact
Reference Study ID Number: GO39775 www.roche.com/about_roche/roche_worldwide.htm888-662-6728 (U.S. only)
global-roche-genentech-trials@gene.com