We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03533283
Recruitment Status : Recruiting
First Posted : May 23, 2018
Last Update Posted : February 21, 2023
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


Condition or disease Intervention/treatment Phase
Non-Hodgkins Lymphoma Drug: Glofitamab Drug: Atezolizumab Drug: Obinutuzumab Drug: Tocilizumab Drug: Polatuzumab Vedotin Drug: 89Zr-Df-IAB22M2C Phase 1 Phase 2

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : May 8, 2018
Estimated Primary Completion Date : November 30, 2024
Estimated Study Completion Date : November 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: RO7082859

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 Name: 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 Name: RO7082859

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 Name: 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 Name: RO7082859

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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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 ]
  2. Change in Maximum Standardized Update Value (SUVmax) Based on 89Zr-PET/CT Scans [ Time Frame: From baseline to Day 13 ]
  3. Change in Peak SUV (SUVpeak) Based on 89Zr-PET/CT Scans [ Time Frame: From baseline to Day 13 ]
  4. Change in Mean SUV (SUVmean) Based on 89Zr-PET/CT Scans [ Time Frame: From baseline to Day 13 ]
  5. Change in CD8 Tumor Volume Based on 89Zr-PET/CT [ Time Frame: From baseline to Day 13 ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. Objective Response Rate (ORR) [ 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. Disease Control Rate (DCR) [ 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. 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) ]
  7. Duration of Complete Response [ 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 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) ]
  9. 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) ]
  10. 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) ]
  11. 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) ]
  12. 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) ]
  13. 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) ]
  14. 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) ]
  15. 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) ]
  16. 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) ]
  17. 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) ]
  18. 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) ]
  19. CD8-Positive T Cell Proliferation [ Time Frame: At pre-defined intervals during the study treatment period (up to 17 cycles; Cycle = 21 days) ]
  20. CD20-Positive B-Cell Reduction [ Time Frame: At pre-defined intervals during the study treatment period (up to 17 cycles; Cycle = 21 days) ]
  21. SUVmax of 89Zr-Df-IAB22M2C [ Time Frame: From baseline to Day 13 ]
  22. SUVpeak of 89Zr-Df-IAB22M2C [ Time Frame: From baseline to Day 13 ]
  23. SUVmean of 89Zr-Df-IAB22M2C [ Time Frame: From baseline to Day 13 ]
  24. Tumor Volume Based on 89Zr-Df-IAB22M2C PET-uptake [ Time Frame: From baseline to Day 13 ]
  25. Quantitation of CD8+ Cells on Biopsy Samples [ Time Frame: From baseline to Day 13 ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03533283


Contacts
Layout table for location contacts
Contact: Reference Study ID Number: NP39488 https://forpatients.roche.com/ 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
Show Show 22 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03533283    
Other Study ID Numbers: NP39488
First Posted: May 23, 2018    Key Record Dates
Last Update Posted: February 21, 2023
Last Verified: February 2023

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Atezolizumab
Obinutuzumab
Antineoplastic Agents
Antineoplastic Agents, Immunological