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

• Status: Recruiting
• Trial end date: 2024-11-30
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, single arm, multicenter, dose finding, Phase Ib study in order to assess the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) for this combination treatment and to evaluate the general safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and preliminary anti-tumor activity of this combination treatment in adult patients.

This study includes an additional open-label imaging feasibility sub-study using a tracer in adult participants with relpased/refractory B-cell non-Hodgkin's lymphoma to image CD8+T-cells at baseline and after treatment with glofitamab, including pre-treatment with obinutuzumab.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Antibodies, Monoclonal; Atezolizumab; Obinutuzumab

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). 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
• 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 targeted 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