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

Purpose

This is a phase I, multicenter, open-label, dose-escalation study of cevostamab 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 cevostamab 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 cevostamab 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 cevostamab 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

ArmDescriptionAssigned Intervention
Experimental
Arm A: Single Step Dose Escalation for Cevostamab 		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.
  • Drug: Cevostamab
    Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
    Other names:
    • BFCR4350A; RO7187797
Experimental
Arm B: Multistep Dose Escalation for Cevostamab 		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.
  • Drug: Cevostamab
    Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
    Other names:
    • BFCR4350A; RO7187797
Experimental
Arm C: Single Step Dose Expansion for Cevostamab 		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.
  • Drug: Cevostamab
    Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
    Other names:
    • BFCR4350A; RO7187797
Experimental
Arm D: Multistep Dose Expansion for Cevostamab 		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.
  • Drug: Cevostamab
    Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
    Other names:
    • BFCR4350A; RO7187797
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 cevostamab and Cycle 1 cevostamab doses for other treatment arms.
  • Drug: Tocilizumab
    Tocilizumab will be administered as premedication during Cycle 1.
    Other names:
    • Actemra/RoActemra
Experimental
Arm F: Single Step Dose Expansion for Cevostamab 		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.
  • Drug: Cevostamab
    Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
    Other names:
    • BFCR4350A; RO7187797
Experimental
Arm G: Multistep Dose Expansion for Cevostamab 		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.
  • Drug: Cevostamab
    Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
    Other names:
    • BFCR4350A; RO7187797

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35249

More Details

Status
Recruiting
Sponsor
Genentech, Inc.

Study Contact

Reference Study ID Number: GO39775 www.roche.com/about_roche/roche_worldwide.htm
888-662-6728 (U.S. only)
global-roche-genentech-trials@gene.com