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

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Status and phase

Active, not recruiting
Phase 2
Phase 1


Non-Hodgkins Lymphoma


Drug: Polatuzumab Vedotin
Drug: Tocilizumab
Drug: Glofitamab
Drug: 89Zr-Df-IAB22M2C
Drug: Obinutuzumab
Drug: Atezolizumab

Study type


Funder types




Details and patient eligibility


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.


280 estimated patients




18+ years old


No Healthy Volunteers

Inclusion and exclusion 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 </=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

Trial design

Primary purpose




Interventional model

Single Group Assignment


None (Open label)

280 participants in 3 patient groups

Experimental group
Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD).
Drug: Obinutuzumab
Drug: Atezolizumab
Drug: Glofitamab
Drug: Tocilizumab
Polatuzumab Vedotin
Experimental group
Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD.
Drug: Obinutuzumab
Drug: Glofitamab
Drug: Polatuzumab Vedotin
Drug: Tocilizumab
Imaging Sub-study
Experimental group
Participants will undergo positive-emission tomography/computed tomography (PET/CT) at screening, followed by an "Imaging Cycle," to replace Cycle 1 of the main study. Eligible participants will have the option roll-over to the atezolizumab arm of the main study from Cycle 2 onwards.
Drug: Obinutuzumab
Drug: 89Zr-Df-IAB22M2C
Drug: Glofitamab

Trial contacts and locations



Central trial contact

Reference Study ID Number: NP39488

Data sourced from

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