U mag meedoen als
- Age >= 18 years
- Patient willing and able to comply with protocol-mandated hospitalization upon administration of the first dose of RO7082859 and also all study-related procedures, in Part III, this includes completion of Patient-reported outcome
- Depending upon study part, a history or status of: 1) a histologically-confirmed hematological malignancy that is expected to express CD20; 2) relapse after or failure to respond to at least one prior treatment regimen; and 3) no available treatment options that are expected to prolong survival (e.g., standard chemotherapy or autologous stem cell transplant [SCT]). Eligible r/r NHL patients include:
• For Parts I and II:
o Grades 1-3b follicular lymphoma (FL); Marginal zone lymphoma (MZL) (splenic; nodal; extra-nodal); Mantle cell lymphoma; Diffuse large B-cell lymphoma (DLBCL); Primary mediastinal B-cell lymphoma (PMBCL); Richter’s transformation; and/or transformed FL
• For Part III expansion cohorts:
o DLBCL(r/r DLBCL [NOS]/high-grade B-cell lymphoma /PMBCL and DLBCL arising from FL /[transformed FL]) cohort: Patients must have relapsed after or failed to respond to at least two prior systemic treatment regimens (including at least one prior regimen containing anthracycline, and at least one containing an anti CD20-directed therapy). The Sponsor retains the option to limit the number of patients enrolled with transformed FL and PMBCL. Patients with Richter’s transformation are not considered eligible for Part III
o FL cohort: Grades 1-3a FL patients must have relapsed after or failed to respond to at least two prior lines of systemic therapy and must have received prior treatment with rituximab and alkylating agents. The Sponsor retains the option to enroll a minimum number of patients who are refractory to both anti-CD20 directed therapy and an alkylating agent.
o For patients in the DLBCL cohort (DLBCL NOS, high-grade B-cell lymphomas, PMBCL or transformed FL) the pathology report for the initial histopathology diagnosis must be provided, if available. Patients with transformed FL must also provide the pathology report at the time of disease transformation, if available. The results of all tests conducted on the tissue at initial diagnosis, including but not limited to tests assessing cell of origin, BCL2 and MYC abnormalities, should be provided if done
- Measurable disease, defined as
- At least one measureable nodal lesion, defined as >1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as >1.0 cm in its longest dimension.
- Able to provide the most recent archival tumor tissue samples (formalin-fixed paraffin-embedded [FFPE] blocks preferred; if not available, slides accepted). Archival tumor tissue samples obtained preferably within 6 months and between the last dose of the last prior cancer regimen and Cycle (C) 1/Day (D)-7)
• In the absence of sufficient archival tissue, a fresh biopsy from a safely accessible site, per Investigator determination , will be requested, providing the patient has more than one measurable target lesion.(Note: if fresh biopsy cannot be obtained, please contact the Medical Monitor).
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Life expectancy (in the opinion of the Investigator) of >= 12 weeks
- Adverse events from prior anti-cancer therapy must have resolved to Grade
- Adequate liver, hematological, and renal function
- Negative serum pregnan
cy test within 7 days prior to study treatment in women of childbearing potential. Women who are not of childbearing potential who are considered to be post-menopausal (>= 12 months of non-therapy amenorrhea) or surgically sterile (absence of ovaries and/or uterus) are not required to have a pregnancy test
- Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection. (Note: Patients whose HBV infection status cannot be determined by serologic test results must be negative for HBV by PCR to be eligible for study participation)
- Negative test results for hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Note: Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation.
- Patients must agree to either remain completely abstinent or to use two effective contraceptive methods that result in a failure rate of
U mag niet meedoen als
- Inability to comply with protocol mandated hospitalization and restrictions
- Patients with chronic lymphocytic leukemia, Burkitt lymphoma and lymphoplasmacytic lymphoma
- Patients with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to Gpt infusion or by clinical judgment in the absence of a positive blood culture
- Patients with known active infection, or reactivation of a latent infection, whether bacterial, viral (including, but not limited to, EBV, cytomegalovirus (CMV), hepatitis B, hepatitis C, and HIV), fungal, mycobacterial, or other pathogens or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing
- Pregnant or breast-feeding or intending to become pregnant during the study
- Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (e.g., anti- Cytotoxic T-lymphocyte-associated protein 4 [CTLA4], anti- Programmed death 1 [PD1] and anti- Programmed death ligand [PDL1]) within 4 weeks or five half-lives of the drug, whichever is shorter, before Gpt infusion on C1/D -7
- History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows:
• Grade >= 3 adverse events with the exception of Grade 3 endocrinopathy managed with replacement therapy
• Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation
- Documented refractoriness to an obinutuzumab monotherapy (M) -containing regimen.
- Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with 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
- Prior solid organ transplantation
- Prior allogeneic SCT
- Autologous SCT within 100 days prior to Gpt infusion
- History of autoimmune disease
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
- Current or past history of central nervous system (CNS) lymphoma
- Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Patients with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits, as judged by the investigator, are allowed.
- 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.
- Major surgery or significant traumatic injury < 28 days prior to the Gpt infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
- Patients with another invasive malignancy in the last 2 years (with the exception of basal cell carcinoma and tumors deemed by the Investigator to be of low likelihood for recurrence)
- Known active or latent bacterial, viral (including hepatitis B, hepatitis C, and HIV), fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or
any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 4 weeks of dosing.
- 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
- Administration of a live, attenuated vaccine within 4 weeks before Gpt 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) within 2 weeks prior to Gpt infusion. Treatment with corticosteroid
• Inhaled and topical steroids are permitted.
- History of illicit drug or alcohol abuse within 12 months prior to screening, in the Investigator’s judgment.
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug.