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NCT Number: NCT03533283

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Non-Hodgkins Lymphoma Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

UZ Gent, Ghent, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Other names: RO7082859, Columvi

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).

Obinutuzumab

Drug

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

Tocilizumab

Drug

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

Other names: Actemra

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).

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.

Primary outcomes

  1. Best Objective Response Rate (ORR) as Measured by Independent Review Committee (IRC)

    Time frame: 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)

  2. Dose Limiting Toxicities (DLTs)

    Time frame: 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

  1. Best ORR as Measured by Investigator

    Time frame: 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)

  2. Best Complete Response (CR) Rate, as Assessed by Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) Scan

    Time frame: 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)

  3. Duration of Complete Response (DOCR)

    Time frame: 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)

  4. Duration of Response (DOR)

    Time frame: 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)

  5. Progression-Free Survival (PFS)

    Time frame: 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)

  6. Event-Free Survival (EFS)

    Time frame: 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)

  7. Time to First Complete Response (TFCR)

    Time frame: 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)

  8. Time to First Overall Response (TFOR)

    Time frame: 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)

  9. Overall Survival (OS)

    Time frame: 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)

  10. Percentage of Participants with Adverse Events (AEs)

    Time frame: 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)

  11. Incidence and Severity of Cytokine Release Syndrome (CRS) Following Glofitamab Administration

    Time frame: 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)

  12. Anti-Drug Antibody (ADA) Formation

    Time frame: 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)

  13. Elimination Half-Life (T1/2) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin

    Time frame: At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)

  14. Area Under the Concentration-Time Curve (AUC) for Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin

    Time frame: At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)

  15. Time to Maximum Observed Serum Concentration (Tmax) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin

    Time frame: At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)

  16. Maximum Observed Serum Concentration (Cmax) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin

    Time frame: At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)

  17. Minimum Serum Concentration (Cmin) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin

    Time frame: At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)

  18. Clearance (CL) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin

    Time frame: At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)

  19. Volume of Distribution at Steady-State (Vss) of Glofitamab Administered in Combination with Atezolizumab or Polatuzumab Vedotin

    Time frame: At pre-defined intervals through the end of study (EoS) visit (to occur within 4 weeks of disease progression)

  20. CD8-Positive T Cell Proliferation

    Time frame: At pre-defined intervals during the study treatment period (up to 17 cycles; Cycle = 21 days)

  21. CD20-Positive B-Cell Reduction

    Time frame: At pre-defined intervals during the study treatment period (up to 17 cycles; Cycle = 21 days)

  22. SUVmax of 89Zr-Df-IAB22M2C (Imaging Sub-study)

    Time frame: From baseline to Day 13

  23. SUVpeak of 89Zr-Df-IAB22M2C (Imaging Sub-study

    Time frame: From baseline to Day 13

  24. SUVmean of 89Zr-Df-IAB22M2C (Imaging Sub-study)

    Time frame: From baseline to Day 13

  25. Tumor Volume Based on 89Zr-Df-IAB22M2C PET-uptake (Imaging Sub-study)

    Time frame: From baseline to Day 13

  26. Quantitation of CD8+ Cells on Biopsy Samples (Imaging Sub-study)

    Time frame: From baseline to Day 13

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2026
Study completion
2026
First posted
May 23, 2018
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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