B-cell non-Hodgkin lymphoma Cancer B-cell lymphoma, unspecified
Conditions
Interventions
All participants will receive pretreatment with a fixed dose of obinutuzumab (Gpt) on Day 1 of Cycle 1 as a safety measure to deplete B cells both in the peripheral blood and in the secondary lymphoid
Sponsors
Genentech, Inc
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Participants who are age =18 years at the time of signing the Informed Consent Form 2. Participants with a history or status of: 2.1. A histologically confirmed hematological malignancy that is expected to express CD20 2.2. No available treatment options that are expected to prolong survival (e.g., standard chemotherapy or autologous stem cell transplant [SCT]) 3. Participants with measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as >1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extra-nodal lesion, defined as >1.0 cm in its longest dimension 4. Participants who are able to provide a fresh biopsy from a safely accessible site, per investigator determination, provided that the participant has more than one measurable target lesion 5. Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 6. Participants with life expectancy (in the opinion of the investigator) of =12 weeks 7. Adverse events from prior anti-cancer therapy must have resolved to Grade 1 or better 8. Participants with adequate liver, hematological and renal function 9. Participants with a negative human immunodeficiency virus (HIV) and hepatitis C virus (HCV) test at screening 10. Participants with a negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection 11. For women of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 18 months after the final dose of obinutuzumab, 3 months after the final dose of tocilizumab (if applicable), or 2 months after the final dose of glofitamab, whichever is longer 12. For men: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agree to refrain from donating sperm during the treatment period and for at least 3 months after the final dose of obinutuzumab, tocilizumab (if applicable), or glofitamab, whichever is longer, to avoid exposing the embryo
Exclusion criteria
Exclusion criteria: 1. Participants who are unable to tolerate subcutaneous injection into the abdomen 2. Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after pretreatment with obinutuzumab or 2 months after the final dose of glofitamab, whichever is longer 3. Participants who are unable to comply with protocol-mandated hospitalizations and restrictions 4. Participants with a known or suspected history of hemophagocytic lymphohistiocytosis (HLH) 5. Participants with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to obinutuzumab pretreatment (Gpt) infusion or by clinical judgment in the absence of a positive blood culture 6. Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing 7. Participants who have had prior treatment with systemic immunotherapeutic agents within 4 weeks or five half-lives of the drug, whichever is shorter, before Gpt infusion on Day 1 of Cycle 1 8. Participants who were previously treated with CD20-CD3 bispecific antibodies (including glofitamab and mosunetuzumab), as this could influence the interpretation of pharmacokinetics and safety 9. Participants with a history of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents 10. Participants who have been treated with standard radiotherapy, any chemotherapeutic agent, any chimeric antigen receptor-modified T-cell (CAR-T) cell therapy, or any other investigational anti-cancer agent (defined as treatment for which there is currently no regulatory authority approved indication) within 4 weeks prior to Gpt infusion 11. Participants with prior solid organ transplantation 12. Participants with prior allogeneic stem cell transplant (SCT) 13. Participants with autologous SCT within 100 days prior to Gpt infusion 14. Participants with a history of autoimmune disease 15. Participants with a history of severe allergic or anaphylactic reactions to monoclonal antibody therapy or recombinant antibody-related fusion proteins 16. Participants with a history of confirmed progressive multifocal leukoencephalopathy 17. Participants who currently have, or who have a history of, central nervous system (CNS) lymphoma 18. Participants who currently have, or who have a history of, CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease 19. Participants with evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders (bronchospasm, obstructive pulmonary disease) and known autoimmune diseases 20. Participants who have undergone major surgery (excluding biopsies) or significant traumatic injury <28 days prior to the Gpt infusion or who anticipate the need for major surgery during study treatment 21. Participants who have had another invasive malignancy in the last 2 years 22. Participants who have significant cardiovascular disease such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina 23. Participants who have rece
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measured using Electronic Data Capture (EDC): 1. Incidence and severity of CRS following glofitamab SC administration, with severity determined according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria by grade and treatment cycle, up to approximately 44 weeks 2. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0), up to approximately 44 weeks 3. Incidence and severity of adverse event of special interest (AESI), up to approximately 44 weeks 4.Targeted vital signs from baseline (up to Day -28) to 44 weeks 5. Targeted clinical laboratory test results from baseline (up to Day -28) to 44 weeks 6. Incidence and severity of dose-limiting toxicities, for Cohort 1: 21 days after the SC dose on Day 15 of Cycle 1; for Cohort 2 and 3: 21 days after the SC dose on Day 1 of Cycle 2 7. Local tolerance at injection sites, including injection-site reactions, up to approximately 44 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured using a validated ELISA method: 1. Serum concentration of glofitamab at specified timepoints at Days 1, 8, and 15 of Cycle 1; Day 1 of Cycle 2, 3, 4, 5, 6, 8, 10 and 12; and treatment completion visit 2. Minimum serum concentration under steady-state conditions within a dosing interval/trough concentration (Cmin/Ctrough) of glofitamab, at Days 1, 8, and 15 of Cycle 1; Day 1 of Cycle 2, 3, 4, 5, 6, 8, 10 and 12; and treatment completion visit 3. Delayed time to Cmax (Tmax) of glofitamab at specified timepoints 4. Maximum serum concentration (Cmax) of glofitamab, at Days 1, 8, and 15 of Cycle 1; Day 1 of Cycle 2, 3, 4, 5, 6, 8, 10 and 12; and treatment completion visit 5. Area under the concentration-time curve (AUC) of glofitamab, at Days 1, 8, and 15 of Cycle 1; Day 1 of Cycle 2, 3, 4, 5, 6, 8, 10 and 12; and treatment completion visit 6. The absolute bioavailability of glofitamab SC administration, at Days 1, 8, and 15 of Cycle 1; Day 1 of Cycle 2, 3, 4, 5, 6, 8, 10 and 12; and treatment completion visit 7. Prevalence of anti-drug antibodies (ADAs) against glofitamab at baseline (up to Day -28) 8. Incidence of ADAs against glofitamab during the study and after treatment completion, at Days 1, 8, and 15 of Cycle 1; Day 1 of Cycle 2, 3, 4, 5, 6, 8, 10 and 12; and treatment completion visit | — |
Countries
Australia, Belgium, Denmark, Italy, Poland, Spain, United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed