Dose-Escalation Study of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)
- Conditions
- Multiple Myeloma
- Registration Number
- NCT03275103
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 420
Inclusion Criteria:<br><br> - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1<br><br> - Life expectancy of at least 12 weeks<br><br> - Participants must have relapsed or refractory (R/R) multiple myeloma (MM) for which<br> no established therapy for MM is appropriate and available or be intolerant to those<br> established therapies<br><br> - Adverse events from prior anti-cancer therapy resolved to Grade < or = 1, except any<br> grade alopecia and/or peripheral sensory or motor neuropathy which must have<br> resolved to Grade < or = 2<br><br> - Measurable disease defined by laboratory test results<br><br> - Female participants of childbearing age must agree to remain abstinent or use<br> reliable contraceptive methods during the treatment period, and at least 5 months<br> after last dose of study drug. Women must refrain from breastfeeding during the same<br> period.<br><br> - Male participants must agree to refrain from donating sperm, to abstain or use a<br> condom during the treatment period, and for at least 2 months after the last dose of<br> tocilizumab (if applicable).<br><br>Exclusion Criteria:<br><br> - Inability to comply with protocol-mandated hospitalization and activities<br> restrictions<br><br> - Pregnant or breastfeeding, or planning to become pregnant during the study or within<br> 5 months after the last dose of cevostamab or within 3 months after the last dose of<br> of tocilizumab (if applicable)<br><br> - Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug<br> conjugate as anti-cancer therapy within 4 weeks before first infusion<br><br> - Prior treatment with systemic immunotherapeutic agents within 12 weeks or 5<br> half-lives of the drug, whichever is shorter, before first infusion<br><br> - Prior treatment with chimeric antigen receptor (CAR) T-cell therapy within 12 weeks<br> before first cevostamab infusion<br><br> - Known treatment-related, immune-mediated adverse events associated with prior<br> immunotherapeutic agents<br><br> - Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other<br> anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of<br> the drug, whichever is shorter, prior to first cevostamab infusion<br><br> - Autologous stem cell transplantation (SCT) within 100 days prior to first infusion<br><br> - Prior allogeneic SCT or solid organ transplantation<br><br> - Absolute plasma cell count exceeding 500/micro L or 5% of the peripheral blood white<br> cells<br><br> - History of autoimmune disease or of confirmed progressive multifocal<br> leukoencephalopathy<br><br> - Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation<br> syndrome (MAS)<br><br> - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy<br> (or recombinant antibody-related fusion proteins)<br><br> - Patients with known history of amyloidosis (e.g., positive Congo Red stain or<br> equivalent in tissue biopsy)<br><br> - Patients with lesions in proximity of vital organs that may develop sudden<br> decompensation/deterioration in the setting of a tumor flare<br><br> - History of other malignancy that could affect compliance with the protocol or<br> interpretation of results<br><br> - Current or past history of central nervous system (CNS) disease, or CNS involvement<br> by MM<br><br> - Significant cardiovascular disease that may limit a patient's ability to adequately<br> respond to a CRS event<br><br> - Symptomatic active pulmonary disease requiring supplemental oxygen<br><br> - Within 14 days prior to first cevostamab infusion: known active bacterial, viral,<br> fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of<br> nail beds) at study enrollment, or any major episode of infection requiring<br> treatment with IV antibiotics within 4 weeks prior to first infusion<br><br> - Positive and quantifiable Epstein-Barr virus (EBV) polymerase chain reaction (PCR)<br> or cytomegalovirus (CMV) PCR prior to first study treatment<br><br> - Known or suspected chronic active EBV infection, acute or chronic hepatitis C virus<br> (HCV) infection<br><br> - Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV)<br> infection<br><br> - Recent major surgery within 4 weeks prior to first infusion<br><br> - Human Immunodeficiency Virus (HIV) positive<br><br> - Any episode of active, symptomatic COVID-19 infection, or requiring treatment with<br> IV antivirals for COVID-19 (not including COVID-19 primary prophylaxis) within 14<br> days, prior to first study treatment<br><br> - Administration of a live, attenuated vaccine within 4 weeks before first cevostamab<br> infusion or anticipation that such a live attenuated vaccine will be required during<br> the study<br><br> - Received systemic immunosuppressive medications (including, but not limited to,<br> cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis<br> factor agents), with the exception of corticosteroid treatment <=10 mg/day<br> prednisone or equivalent within 2 weeks prior to first dose of cevostamab and, if<br> applicable, tocilizumab premedication prior to first dose of cevostamab<br><br> - History of illicit drug or alcohol abuse within 12 months prior to screening<br><br> - Any medical condition or laboratory test abnormality that precludes the<br> participant's safe participation in and completion of the study, or which could<br> affect compliance with the protocol or interpretation of results
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Percentage of Participants with Adverse Events (AEs);Percentage of Participants With Dose-Limiting Toxicities (DLTs);Arms E and J Only: Incidence and Severity of Cytokine-release Syndrome (CRS) Following Tocilizumab Premedication Followed by Treatment with Cevostamab
- Secondary Outcome Measures
Name Time Method Cmin of Tocilizumab;Clearance (CL) of Cevostamab;CL of Tocilizumab;Volume of Distribution at Steady State (Vdss) of Cevostamab;Vdss of Tocilizumab;Serum Concentration of Cevostamab;Serum Concentration of Tocilizumab;Objective Response Rate (ORR);Duration of Response;Change from Baseline in the Presence Anti-Drug Antibodies (ADAs);Area Under the Concentration-Time Curve (AUC) of Cevostamab;AUC of Tocilizumab;Maximum Observed Serum Concentration (Cmax) of Cevostamab;Cmax of Tocilizumab;Minimum Observed Serum Concentration (Cmin) of Cevostamab