A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Registration Number
- NCT04910568
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 184
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> - Agreement to provide bone marrow biopsy and aspirate samples<br><br> - Resolution of adverse events from prior anti-cancer therapy to Grade <=1<br><br> - Measurable disease<br><br> - For women of childbearing potential: agreement to remain abstinent or use<br> contraception, during the treatment period (including treatment interruptions) and<br> for at least 5 months after the last dose of cevostamab and at least 3 months after<br> the last dose of tocilizumab was administered<br><br> - For men: agreement to remain abstinent or use a condom, and agreement to refrain<br> from donating sperm, during the treatment period, and for at least 2 months after<br> the last dose of tocilizumab was administered to avoid exposing the embryo and<br> sexual partner Additional Arm A-Specific Inclusion Criteria<br><br> - Diagnosis of R/R MM for which no established therapy for MM is appropriate and<br> available, or intolerance to those established therapies Additional Arm B-Specific<br> Inclusion Criteria<br><br> - For Cohort B1S: Participants with R/R MM who have received at least two prior lines<br> of treatment<br><br> - For Cohort B2S and additional cohorts: Participants with R/R MM who have received at<br> least 1 prior line of treatment<br><br> - Agreement to comply with all requirements of the pomalidomide pregnancy prevention<br> program<br><br> - For women of childbearing potential: agreement to remain abstinent or use two<br> reliable methods of contraception starting at least 4 weeks prior to, during the<br> treatment period, and for at least 4 weeks after the last dose of pomalidomide was<br> administered<br><br> - For men: agreement to remain abstinent or use a condom during the treatment period<br> and for at least 4 weeks after the last dose of pomalidomide, (even if he has<br> undergone a successful vasectomy) and agreement to refrain from donating sperm and<br> blood during this same period Additional Arm C-Specific Inclusion Criteria<br><br> - For Cohort C1S: Participants with R/R MM who have received at least two prior lines<br> of treatment<br><br> - For Cohort C2S and additional cohorts: Participants with R/R MM who have received at<br> least 1 prior line of therapy<br><br> - For women of childbearing potential: agreement to remain abstinent or use<br> contraceptive methods during the treatment period and for at least 102 days after<br> the last dose of daratumumab was administered<br><br> - For men: agreement to remain abstinent or use a condom during the treatment period<br> and for at least 102 days after the last dose of daratumumab was administered to<br> avoid exposing the embryo, and agreement to refrain from donating sperm during this<br> same period<br><br>Exclusion Criteria:<br><br> - Prior treatment with cevostamab or another agent targeting FcRH5<br><br> - Inability to comply with protocol-mandated hospitalization and activities<br> restrictions<br><br> - Pregnant or breastfeeding, or intending to become pregnant during the study or<br> within 5 months after the last dose of cevostamab or within 3 months after the last<br> dose of tocilizumab (if applicable).<br><br> - Prior use of any monoclonal antibody, radioimmunoconjugate, or<br> antibody-drugconjugate as anti-cancer therapy within 4 weeks before first study<br> treatment, except for the use of non-myeloma therapy<br><br> - Prior treatment with systemic immunotherapeutic agents, including, but not limited<br> to, cytokine therapy and anti-CTLA4, anti-PD-1, and antiPD-L1 therapeutic antibodies<br> within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first<br> study treatment<br><br> - Prior treatment with chimeric antigen receptor T (CAR T)-cell therapy within 12<br> weeks before first study treatment<br><br> - Treatment with radiotherapy within 4 weeks (systemic radiation) or 14 days (focal<br> radiation) prior to first study treatment<br><br> - Treatment with any chemotherapeutic agent or other anti-cancer agent<br> (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever<br> is shorter, prior to first study treatment<br><br> - Autologous SCT within 100 days prior to first study treatment<br><br> - Prior allogeneic stem cell transplant(ation) (SCT)<br><br> - Circulating plasma cell count exceeding 500/micro L or 5% of the peripheral blood<br> white cells<br><br> - Prior solid organ transplantation<br><br> - History of autoimmune disease<br><br> - History of confirmed progressive multifocal leukoencephalopathy<br><br> - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy<br><br> - Known history of amyloidosis<br><br> - 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 within 2 years prior to screening<br><br> - Known treatment-related, immune-mediated adverse events associated with prior<br> checkpoint inhibitors<br><br> - Current or past history of central nervous system (CNS) disease, such as stroke,<br> epilepsy, CNS vasculitis, neurodegenerative disease, or CNS involvement by MM<br><br> - Significant cardiovascular disease<br><br> - Symptomatic active pulmonary disease or requiring supplemental oxygen<br><br> - Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection<br><br> - Known or suspected chronic active Epstein-Barr virus (EBV) infection<br><br> - Recent major surgery within 4 weeks prior to first study treatment<br><br> - Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV)<br> infection<br><br> - Acute or chronic hepatitis C virus (HCV) infection<br><br> - Known history of Grade >= 3 CRS or immune effector cell-associated neurotoxicity<br> syndrome (ICANS) with prior bispecific therapies<br><br> - Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation<br> syndrome (MAS)<br><br> - Active symptomatic coronavirus disease 2019 (COVID-19) infection at study enrollment<br> or requiring treatment with intravenous (IV) antiviral where the last dose of IV<br> antiviral treatment was given within 14 days prior to first study treatment.<br> Patients with active COVID-19 infection must have clinical recovery and two negative<br> antigen tests at least 24 hours apart prior to first study treatment<br><br> - Positive and quantifiable EBV polymerase chain reaction (PCR) or Cytomegalovirus<br> (CMV) PCR prior to first study treatment<br><br> - Known history of HIV seropositivity<br><br> - Administration of a live, attenuated vaccine within 4 weeks before first study<br> treatment or anticipation that such a live attenuated vaccine will be required<br> during the study<br><br> - Treatment with systemic immunosuppressive medications, with the exception of<br> corticosteroid treatment <=10 mg/day prednisone or equivalent, within 2 weeks prior<br> to first study treatment<br><br> - History of illicit drug or alcohol abuse within 12 months prior to screening, in the<br> investigator's judgment Additional Arm B-Specific Exclusion Criteria<br><br> - Pregnant or breastfeeding, or intending to become pregnant 4 weeks prior to<br> initiation of study treatment, during the study, (including treatment interruptions)<br> or within 4 weeks after the last dose of pomalidomide<br><br
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Recommended Phase II Dose (RP2D);Percentage of Participants with Adverse Events;Percentage of Dose Interruptions;Percentage of Dose Reductions;Percentage of Dose Intensity;Percentage of Treatment Discontinuation
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR);Complete Response/Stringent Complete Response (CR/sCR) Rate;Rate of Very Good Partial Response (VGPR) or Better;Progression-free Survival (PFS);Duration of Response (DOR);Time to First Response (for Participants who Achieve a Response of Partial Response (PR) or Better);Time to Best Response (for Participants who Achieve a Response of PR or Better);Minimal Residual Disease (MRD) Negativity;Overall Survival (OS);Serum Concentration of Cevostamab at Specified Timepoints;Total Exposure (Area Under the Concentration-time Curve [AUC]) of Cevostamab;Maximum Observed Serum Concentration (Cmax) of Cevostamab;Minimum Observed Serum Concentration (Cmin) of Cevostamab;Clearance of Cevostamab;Volume of Distribution at Steady State of Cevostamab;Number of Anti-drug Antibody (ADAs) Against Cevostamab at Baseline;Percentage of Participants with ADAs Against Cevostamab During the Study;Serum Concentration of Pomalidomide;Serum Concentration of Daratumumab