An Open-Label Phase lB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

This is an interventional treatment trial for Non-Hodgkins Lymphoma Read More

Main Inclusion Criteria

• Histologically-confirmed hematologic malignancy that is expected to express CD20 (Relapsed after or refractory to respond to at least one prior treatment regimen; no available treatment options that are expected to prolong survival or patients refusing chemotherapy or autologous stem cell transplant (SCT). Note: The expansion part is restricted to relapsed/refractory follicular lymphoma (r/r FL) and relapsed/refractory diffuse large B cell lymphoma (r/r DLBCL))
• At least one measurable target lesion
• Fresh pre-treatment biopsy, but if this cannot be taken, a previous archived biopsy from metastatic lesion can be taken as replacement if it is not older than 6 months and not confounded by major events (progression, treatment)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate organ function (liver, hematological, renal)
• Negative test results for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV)

Inclusion Criteria Specific to Imaging Substudy

• At least two measurable target lesions
• Able to provide two fresh tumor biopsies (baseline and on-treatment)

Main Exclusion Criteria

• Participants with Chronic Lymphocytic Leukemia (CLL), acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma, Richter's transformation, CD20-positive ALL, Burkitt lymphoma, or lymphoplasmacytic lymphoma
• Current > Grade 1 peripheral neuropathy (only for participants being treated in the polatuzumab vedotin arm)
• Patients with known active infection, or reactivation of a latent infection within 4 weeks prior to Obinutuzumab (Gpt) infusion
• Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
• History of leptomeningeal disease
• Current or past history of central nervous system (CNS) lymphoma
• Current or past history of CNS disease
• Major surgery or significant traumatic injury </=28 days prior to Gpt infusion
• Significant cardiovascular disease or significant pulmonary disease
• Active or history of autoimmune disease or immune deficiency (with exceptions, e.g. hypothyroidism and Diabetes mellitus Type 1)
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Treatment with any other standard anti-cancer radiotherapy / chemotherapy including investigational therapy within 4 weeks prior to Gpt infusion
• Prior solid organ transplantation
• Prior allogenic stem cell transplant (SCT)
• Autologous SCT within 100 days prior to Gpt infusion
• Documented refractoriness to an obinutuzumab-monotherapy regimen
• Prior treatment with anti-cancer/lymphoma therapies and systemic immunotherapeutic/immunostimulating agents within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to Gpt infusion
• Any history of immune related >/= Grade 3 adverse events (AE) with the exception of endocrinopathy managed with replacement therapy
• Ongoing corticosteroid use >25 milligrams/day of prednisone or equivalent within 4 weeks prior to and during study treatment
• Treatment with systemic immunosuppressive medication
• Administration of a live, attenuated vaccine within 4 weeks prior to Gpt infusion or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after last dose of study treatment

Exclusion Criteria Specific to Imaging Substudy

• Circulating lymphoma cells, defined by out of range (high) absolute lymphocyte count and/or the presence of abnormal/malignant cells in the peripheral blood differential signifying circulating lymphoma cell
• Participants who have had splenectomy or functional asplenia that could compromise protocol objectives