Clinical Trials /

A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma

NCT04910568

Description:

This Phase Ib, multicenter, open-label study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cevostamab which will be administered to participants with relapsed or refractory multiple myeloma (R/R MM) via intravenous (IV) infusion using a modified weekly schedule.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma
  • Official Title: An Open-Label, Multicenter, Phase Ib Trial Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Patients With Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: GO42552
  • SECONDARY ID: 2021-000238-33
  • NCT ID: NCT04910568

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CevostamabCevostamab Single-Agent Safety Run-In (Arm A1S) and Single-Agent Expansion (Arm A1E)
TocilizumabActemra/RoActemraCevostamab Single-Agent Safety Run-In (Arm A1S) and Single-Agent Expansion (Arm A1E)

Purpose

This Phase Ib, multicenter, open-label study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cevostamab which will be administered to participants with relapsed or refractory multiple myeloma (R/R MM) via intravenous (IV) infusion using a modified weekly schedule.

Trial Arms

NameTypeDescriptionInterventions
Cevostamab Single-Agent Safety Run-In (Arm A1S) and Single-Agent Expansion (Arm A1E)ExperimentalArm A1S is a safety run-in arm evaluating Cevostamab administered in 28-day cycles on a modified weekly schedule. Upon completion of Arm A1S, Arm A1E, an expansion cohort may be opened. Participants will be treated with single-agent cevostamab administered in 28-day cycles on a modified weekly schedule.
  • Cevostamab
  • Tocilizumab

Eligibility Criteria

        Inclusion Criteria:

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

          -  Life expectancy of at least 12 weeks

          -  Diagnosis of R/R MM for which no established therapy for MM is appropriate and
             available, or intolerance to those established therapies

          -  Agreement to provide bone marrow biopsy and aspirate samples

          -  Resolution of adverse events from prior anti-cancer therapy to Grade <=1

          -  Measurable disease

        Exclusion Criteria:

          -  Prior treatment with cevostamab or another agent with the same target

          -  Pregnant or breastfeeding, or intending to become pregnant during the study or within
             3 months after the 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 study treatment, except for the use
             of non-myeloma therapy

          -  Prior treatment with systemic immunotherapeutic agents, including, but not limited to,
             cytokine therapy and anti-CTLA4, anti-PD-1, and antiPD-L1 therapeutic antibodies
             within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first study
             treatment

          -  Prior treatment with chimeric antigen receptor T (CAR T)-cell therapy within 12 weeks
             before first cevostamab infusion

          -  Prior allogeneic stem cell transplant(ation) (SCT)

          -  Known treatment-related, immune-mediated adverse events associated with prior
             checkpoint inhibitors

          -  Current or past history of central nervous system (CNS) disease, such as stroke,
             epilepsy, CNS vasculitis, neurodegenerative disease, or CNS involvement by MM

          -  Significant cardiovascular disease

          -  Symptomatic active pulmonary disease or requiring supplemental oxygen

          -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection

          -  Known or suspected chronic active Epstein-Barr virus (EBV) infection

          -  Recent major surgery within 4 weeks prior to first study treatment

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

          -  Acute or chronic hepatitis C virus (HCV) infection

          -  Known history of HIV seropositivity

          -  Administration of a live, attenuated vaccine within 4 weeks before first study
             treatment or anticipation that such a live attenuated vaccine will be required during
             the study

          -  Treatment with systemic immunosuppressive medications, with the exception of
             corticosteroid treatment <=10 mg/day prednisone or equivalent, within 2 weeks prior to
             first study treatment

          -  History of illicit drug or alcohol abuse within 12 months prior to screening, in the
             investigator's judgment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Adverse Events
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:
Measure:Complete Response/Stringent Complete Response (CR/sCR) Rate
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:
Measure:Rate of Very Good Partial Response (VGPR) or Better
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:
Measure:Progression-free Survival (PFS)
Time Frame:Baseline to disease progression or death from any cause, whichever occurs first (up to approximately 3 years)
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:From first partial response (PR) until disease progression or death from any cause, whichever occurs first (up to approximately 3 years)
Safety Issue:
Description:
Measure:Time to First Response (for Participants who Achieve a Response of Partial Response (PR) or Better)
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:
Measure:Time to Best Response (for Participants who Achieve a Response of PR or Better)
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:
Measure:Minimal Residual Disease (MRD) Negativity
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Baseline up until death from any cause (up to approximately 3 years)
Safety Issue:
Description:
Measure:Serum Concentration of Cevostamab at Specified Timepoints
Time Frame:From Cycle 1 Day 1 through Cycle 13 Day 1 and at end of study treatment (up to approximately 3 years). Each cycle=28 days
Safety Issue:
Description:
Measure:Total Exposure (Area Under the Concentration-time Curve [AUC]) of Cevostamab
Time Frame:From Cycle 1 Day 1 through Cycle 13 Day 1 and at end of study treatment (up to approximately 3 years). Each cycle=28 days
Safety Issue:
Description:
Measure:Maximum Observed Serum Concentration (Cmax) of Cevostamab
Time Frame:From Cycle 1 Day 1 through Cycle 13 Day 1 and at end of study treatment (up to approximately 3 years). Each cycle=28 days
Safety Issue:
Description:
Measure:Minimum Observed Serum Concentration (Cmin) of Cevostamab
Time Frame:From Cycle 1 Day 1 through Cycle 13 Day 1 and at end of study treatment (up to approximately 3 years). Each cycle=28 days
Safety Issue:
Description:
Measure:Clearance of Cevostamab
Time Frame:From Cycle 1 Day 1 through Cycle 13 Day 1 and at end of study treatment (up to approximately 3 years). Each cycle=28 days
Safety Issue:
Description:
Measure:Volume of Distribution at Steady State of Cevostamab
Time Frame:From Cycle 1 Day 1 through Cycle 13 Day 1 and at end of study treatment (up to approximately 3 years). Each cycle=28 days
Safety Issue:
Description:
Measure:Number of Anti-drug Antibody (ADAs) Against Cevostamab at Baseline
Time Frame:Baseline
Safety Issue:
Description:
Measure:Percentage of Participants with ADAs Against Cevostamab During the Study
Time Frame:Up to approximately 3 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Genentech, Inc.

Last Updated

June 25, 2021