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

An Open-Label, Multi-Center, Phase IB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin (Plus a Single Pre-Treatment Dose of Obinutuzumab) in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Hodgkins Lymphoma
• Intervention / Treatment: Drug: Glofitamab; Drug: Atezolizumab; Drug: Obinutuzumab; Drug: Tocilizumab; Drug: Polatuzumab Vedotin; Drug: 89Zr-Df-IAB22M2C

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • UZ Gent
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital Skejby
  • København Ø, Denmark, 2100
    • Rigshospitalet
  • Odense C, Denmark, 5000
    • Odense Universitetshospital
• Israel
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Karem Hospital
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center-Beilinson Campus
  • Ramat Gan, Israel, 52621
    • Chaim Sheba Medical Center
• Italy
  • Campania
    • Naples, Campania, Italy, 80131
      • Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Policlinico S.Orsola-Malpighi
  • Lombardy
    • Bergamo, Lombardy, Italy, 24127
      • Asst Papa Giovanni XXIII
    • Milan, Lombardy, Italy, 20133
      • Fond. IRCCS Istituto Nazionale Tumori
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08907
    • Hospital Duran i Reynals
  • Madrid, Spain, 28040
    • START Madrid-FJD, Hospital Fundacion Jimenez Diaz
  • Málaga, Spain, 29010
    • Hospital Clínico Universitario Virgen de la Victoria
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • The HOPE Clinical Trials Unit
  • London, United Kingdom, W1T 7HA
    • University College London Hospitals Nhs Foundation Trust
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab; Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD).	Drug: Glofitamab; Glofitamab will be administered through IV infusion every 3 weeks (Q3W) beginning Cycle 1, Day 1, for up to 17 cycles (Cycle = 21 days). Step-up dosing, in which an initial lower dose will be followed by a higher dose 1 week later, will be considered for the initial treatment phase and for Cycle 9 of the re-treatment phase.; Other Names: RO7082859; Columvi; Drug: Atezolizumab; Atezolizumab will be administered in combination with Glofitamab through IV infusion Q3W from Cycle 2, Day 1, for up to 16 cycles (Cycle = 21 days).; Drug: Obinutuzumab; Obinutuzumab will be administered once, through IV infusion, at a fixed dose 7 days before the first dose of Glofitamab.; Drug: Tocilizumab; Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).; Other Names: Actemra
Experimental: Polatuzumab Vedotin; Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD.	Drug: Glofitamab; Glofitamab will be administered through IV infusion every 3 weeks (Q3W) beginning Cycle 1, Day 1, for up to 17 cycles (Cycle = 21 days). Step-up dosing, in which an initial lower dose will be followed by a higher dose 1 week later, will be considered for the initial treatment phase and for Cycle 9 of the re-treatment phase.; Other Names: RO7082859; Columvi; Drug: Obinutuzumab; Obinutuzumab will be administered once, through IV infusion, at a fixed dose 7 days before the first dose of Glofitamab.; Drug: Tocilizumab; Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).; Other Names: Actemra; Drug: Polatuzumab Vedotin; Polatuzumab vedotin will be administered in combination with Glofitamab (on different days) Q3W from Cycle 1, Day 2, for up to 12 cycles (Cycle = 21 days).
Experimental: Imaging Sub-study; 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: Glofitamab; Glofitamab will be administered through IV infusion every 3 weeks (Q3W) beginning Cycle 1, Day 1, for up to 17 cycles (Cycle = 21 days). Step-up dosing, in which an initial lower dose will be followed by a higher dose 1 week later, will be considered for the initial treatment phase and for Cycle 9 of the re-treatment phase.; Other Names: RO7082859; Columvi; Drug: Obinutuzumab; Obinutuzumab will be administered once, through IV infusion, at a fixed dose 7 days before the first dose of Glofitamab.; Drug: 89Zr-Df-IAB22M2C; Participants will receive 89Zr-Df-IAB22M2C (Cycle 1 only) prior to obinutuzumab pre-treatment and again on Day 10 after dosing with glofitamab, followed by PET/CT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose Limiting Toxicities (DLTs)	Atezolizumab Arm: During DLT period of 21 days (or up to 42 days in the case of cycle delay), starting on Day 1, Cycle 2; Polatuzumab Vedotin Arm: During 5-week DLT period starting Cycle 1, Day 8
Best Objective Response Rate (ORR) as Measured by Independent Review Committee (IRC)	Baseline until the end of treatment (13 to 14 months), then ever 3 months until end of study visit (to occur within 4 weeks of disease progression)

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Adverse Events (AEs)	Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Anti-Drug Antibody (ADA) Formation	Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Duration of Response (DOR)	Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Time to First Complete Response (TFCR)	Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Time to First Overall Response (TFOR)	Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Progression-Free Survival (PFS)	Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Overall Survival (OS)	Baseline through end of survival follow-up phase (survival follow-up is every 3 months until death, lost to follow-up, withdrawal of consent, or study termination)
Elimination Half-Life (T1/2) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin	At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Area Under the Concentration-Time Curve (AUC) for Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin	At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Time to Maximum Observed Serum Concentration (Tmax) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin	At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Maximum Observed Serum Concentration (Cmax) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin	At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Minimum Serum Concentration (Cmin) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin	At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Clearance (CL) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin	At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
Volume of Distribution at Steady-State (Vss) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin	At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)
CD8-Positive T Cell Proliferation	At pre-defined intervals during the study treatment period (up to 17 cycles; Cycle = 21 days)
CD20-Positive B-Cell Reduction	At pre-defined intervals during the study treatment period (up to 17 cycles; Cycle = 21 days)
Best ORR as Measured by Investigator	Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Best Complete Response (CR) Rate, as Assessed by Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) Scan	Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Duration of Complete Response (DOCR)	Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Event-Free Survival (EFS)	Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
Incidence and Severity of Cytokine Release Syndrome (CRS) Following Glofitamab Administration	Baseline until end of treatment (13 to 14 months), then every 3 months until end of study visit (to occur within 4 weeks of disease progression)
SUVmax of 89Zr-Df-IAB22M2C (Imaging Sub-study)	From baseline to Day 13
SUVpeak of 89Zr-Df-IAB22M2C (Imaging Sub-study	From baseline to Day 13
SUVmean of 89Zr-Df-IAB22M2C (Imaging Sub-study)	From baseline to Day 13
Tumor Volume Based on 89Zr-Df-IAB22M2C PET-uptake (Imaging Sub-study)	From baseline to Day 13
Quantitation of CD8+ Cells on Biopsy Samples (Imaging Sub-study)	From baseline to Day 13

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Hutchings M, Sureda A, Bosch F, Larsen TS, Corradini P, Avigdor A, Terol MJ, Dominguez AR, Pinto A, Skarbnik A, Cordoba R, Jorgensen JM, Zinzani PL, Leung W, Bottos A, Li D, Relf J, Tandon M, Sellam G, Gritti G. Efficacy and Safety of Glofitamab Plus Polatuzumab Vedotin in Relapsed/Refractory Large B-Cell Lymphoma Including High-Grade B-Cell Lymphoma: Results From a Phase Ib/II Trial. J Clin Oncol. 2025 Dec 20;43(36):3788-3798. doi: 10.1200/JCO-25-00992. Epub 2025 Oct 20.

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2018
• Primary Completion (Estimated): October 16, 2026
• Study Completion (Estimated): October 16, 2026

Study Registration Dates

• First Submitted: May 4, 2018
• First Submitted That Met QC Criteria: May 11, 2018
• First Posted (Actual): May 23, 2018

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Non-Hodgkin; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunoconjugates; tocilizumab; obinutuzumab; atezolizumab; polatuzumab vedotin; glofitamab
• Other Study ID Numbers: NP39488

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No