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

Launched by HOFFMANN-LA ROCHE · May 11, 2018

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment for adults with relapsed or refractory B-cell non-Hodgkin's lymphoma, which means their cancer has returned or has not responded to previous treatments. The study is testing two combinations of medications: Glofitamab with Atezolizumab or Polatuzumab Vedotin. The main goals are to find the safest and most effective doses of these drugs, check how well they work, and monitor any side effects. Additionally, there will be a special sub-study using imaging to take pictures of certain immune cells before and after treatment to see how the body responds.

To be eligible for this trial, participants must have a confirmed diagnosis of certain types of B-cell non-Hodgkin's lymphoma and have already tried at least one other treatment. They should have measurable cancer that doctors can see and must meet specific health criteria, such as having good organ function and no active infections. Participants can expect to receive the investigational treatment and undergo regular monitoring, including biopsies and imaging tests. It’s important to note that this study is currently active but not recruiting new participants.

Gender

ALL

Eligibility criteria

• • 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))
• • Dose-escalation: Grades 1-3b relapsed or refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL) (nodal; extra-nodal; or splenic), diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 rearrangements (double-hit lymphoma), HGBCL not otherwise specified (NOS), DLBCL arising from FL (transformed FL)
• • Dose-expansion: R/R LBCL, including DLBCL NOS, DLBCL arising from FL (transformed FL), PMBCL, HGBCL with MYC and BCL2 and/or BCL6 rearrangements (i.e., double-hit and triple-hit lymphomas), and HGBCL NOS
• • 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