Clinical trial NCT03275103: Dose-Escalation Study of Cevostamab 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 Cevostamab (BFCR4350A) in Patients With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2017-09-07
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).


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 5 months after last dose of study drug. Women must refrain from breastfeeding during the same period.
* Male participants must agree to refrain from donating sperm, to abstain or use a condom during the treatment period, and for at least 2 months after the last dose of tocilizumab (if applicable).

Exclusion Criteria:

* Inability to comply with protocol-mandated hospitalization and activities restrictions
* Pregnant or breastfeeding, or planning to become pregnant during the study or within 5 months after the last dose of cevostamab or within 3 months after the last dose of of tocilizumab (if applicable)
* 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
* Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
* 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
* Positive and quantifiable Epstein-Barr virus (EBV) polymerase chain reaction (PCR) or cytomegalovirus (CMV) PCR prior to first study treatment
* Known or suspected chronic active EBV infection, acute or chronic hepatitis C virus (HCV) infection
* Positive serologic or 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
* Any episode of active, symptomatic COVID-19 infection, or requiring treatment with IV antivirals for COVID-19 (not including COVID-19 primary prophylaxis) within 14 days, prior to first study treatment
* Administration of a live, attenuated vaccine within 4 weeks before first cevostamab infusion or anticipation that such a live attenuated vaccine will be required during the study
* Received systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), with the exception of corticosteroid treatment \<=10 mg/day prednisone or equivalent within 2 weeks prior to first dose of cevostamab and, if applicable, tocilizumab premedication prior to first dose of cevostamab
* 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

Primary outcomes:
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to approximately 8 years
measure: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Up to approximately 8 years
measure: Arms E and J Only: Incidence and Severity of Cytokine-release Syndrome (CRS) Following Tocilizumab Premedication Followed by Treatment with Cevostamab
timeFrame: Up to approximately 8 years
Secondary outcomes:
measure: Area Under the Concentration-Time Curve (AUC) of Cevostamab
timeFrame: Up to approximately 8 years
measure: AUC of Tocilizumab
timeFrame: Up to approximately 8 years
measure: Maximum Observed Serum Concentration (Cmax) of Cevostamab
timeFrame: Up to approximately 8 years
measure: Cmax of Tocilizumab
timeFrame: Up to approximately 8 years
measure: Minimum Observed Serum Concentration (Cmin) of Cevostamab
timeFrame: Up to approximately 8 years
measure: Cmin of Tocilizumab
timeFrame: Up to approximately 8 years
measure: Clearance (CL) of Cevostamab
timeFrame: Up to approximately 8 years
measure: CL of Tocilizumab
timeFrame: Up to approximately 8 years
measure: Volume of Distribution at Steady State (Vdss) of Cevostamab
timeFrame: Up to approximately 8 years
measure: Vdss of Tocilizumab
timeFrame: Up to approximately 8 years
measure: Serum Concentration of Cevostamab
timeFrame: Up to approximately 8 years
measure: Serum Concentration of Tocilizumab
timeFrame: Up to approximately 8 years
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 8 years
measure: Duration of Response
timeFrame: Up to approximately 8 years
measure: Change from Baseline in the Presence Anti-Drug Antibodies (ADAs)
timeFrame: Up to approximately 8 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic Hospital - Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology - Nashville
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Pamplona/iruña
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: