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

NCT03533283 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: NP39488
• Study Type: interventional
• Target: 211
• Locations: 6 countries
• Sites: 19

Brief 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.

Conditions

Non-Hodgkins Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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)

• 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

Secondary Outcomes (26)

• 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)

• 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)

• 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)

Study Arms (3)

Atezolizumab

EXPERIMENTAL

Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD).

Drug: Glofitamab; Drug: Atezolizumab; Drug: Obinutuzumab; Drug: Tocilizumab

Polatuzumab Vedotin

EXPERIMENTAL

Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD.

Drug: Glofitamab; Drug: Obinutuzumab; Drug: Tocilizumab; Drug: Polatuzumab Vedotin

Imaging Sub-study

EXPERIMENTAL

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; Drug: Obinutuzumab; Drug: 89Zr-Df-IAB22M2C

Interventions

Glofitamab DRUG

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.

Also known as: RO7082859, Columvi

Atezolizumab; Imaging Sub-study; Polatuzumab Vedotin

Atezolizumab DRUG

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).

Atezolizumab

Obinutuzumab DRUG

Obinutuzumab will be administered once, through IV infusion, at a fixed dose 7 days before the first dose of Glofitamab.

Atezolizumab; Imaging Sub-study; Polatuzumab Vedotin

Tocilizumab DRUG

Tocilizumab will be administered as necessary to treat cytokine release syndrome (CRS).

Also known as: Actemra

Atezolizumab; Polatuzumab Vedotin

Polatuzumab Vedotin DRUG

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).

Polatuzumab Vedotin

89Zr-Df-IAB22M2C DRUG

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.

Imaging Sub-study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (19)

UZ Gent

Ghent, 9000, Belgium

Location

Aarhus Universitetshospital Skejby

Aarhus N, 8200, Denmark

Location

Rigshospitalet

København Ø, 2100, Denmark

Location

Odense Universitetshospital

Odense C, 5000, Denmark

Location

Hadassah Ein Karem Hospital

Jerusalem, 9112001, Israel

Location

Rabin Medical Center-Beilinson Campus

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Istituto Nazionale Tumori Irccs Fondazione g. Pascale

Naples, Campania, 80131, Italy

Location

Policlinico S.Orsola-Malpighi

Bologna, Emilia-Romagna, 40138, Italy

Location

Asst Papa Giovanni Xxiii

Bergamo, Lombardy, 24127, Italy

Location

Fond. IRCCS Istituto Nazionale Tumori

Milan, Lombardy, 20133, Italy

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Duran i Reynals

Barcelona, 08907, Spain

Location

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

The HOPE Clinical Trials Unit

Leicester, LE1 5WW, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, W1T 7HA, United Kingdom

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 41115257 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

glofitamab; atezolizumab; obinutuzumab; tocilizumab; polatuzumab vedotin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2018
• First Posted: May 23, 2018
• Study Start: May 8, 2018
• Primary Completion (Estimated): October 16, 2026
• Study Completion (Estimated): October 16, 2026
• Last Updated: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

IL (3); IT (4); BE (1); DK (3); GB (3); ES (5)