A Study of Glofitamab in Combination With Rituximab or Obinutuzumab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP), or Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (CHP) in Participants With Non-Hodgkin Lymphomas or With DLBCL

NCT ID: NCT03467373

Last Updated: 2025-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 111 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-13
• Study Completion Date: 2024-12-02

Brief Summary

This is a phase 1B, multi-center, dose-finding study of glofitamab administered in combination with obinutuzumab (Gazyva; [G]), rituximab (R) and standard doses of CHOP (G/R-CHOP or R-CHOP) in participants with r/r NHL and G/R CHOP or Pola-R-CHP in participants with untreated diffuse large B-cell lymphoma (DLBCL). Evaluating the safety, preliminary activity, pharmacokinetic (PK), and pharmacodynamic effects of this combination will be the main objectives of this study. The study is divided in two parts:

• Part I: Dose finding in participants with r/r NHL; test use of G vs R in Cycle 1
• Part II: Dose Expansion. The maximum tolerated dose or optimal biological dose (MTD or OBD) will be further assessed in participants with untreated DLBCL (>18 years of age with an age-adjusted International Prognostic Index (IPI) of 2-5). Glofitamab will be studied in combination with R-CHOP and Pola-R-CHP.

Conditions

B-Cell Lymphoma; Non-Hodgkin Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Dose Escalation r/r NHL

Dose finding in participants with r/r NHL: the study will explore different doses of glofitamab in the induction period, starting at a dose of 70 mcg administered in combination with standard of care doses of G/R CHOP and R-CHOP every 3 weeks (Q3W). Participants with r/r NHL will receive 6 cycles of induction treatment (G/R-CHOP). Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. Participants who achieve a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOInd) may optionally receive post-induction treatment (referred to as maintenance) with glofitamab alone.

The use of G versus R in Cycle 1 will be compared in parallel dose escalation cohorts.

Group Type: EXPERIMENTAL

Glofitamab

Intervention Type: DRUG

Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards.

Obinutuzumab (G)

Intervention Type: DRUG

Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only

Rituximab (R)

Intervention Type: DRUG

Rituximab will be administered as an IV infusion at a dose of 375 mg/m\^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP).

Tocilizumab

Intervention Type: DRUG

Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide 750 mg/m\^2 administered IV on Day 1 of each 21-day cycle

Doxorubicin

Intervention Type: DRUG

Doxorubicin 50 mg/m\^2 administered IV on Day 1 of each 21-day cycle

Vincristine

Intervention Type: DRUG

Vincristine 1.4 mg/m\^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg

Prednisone

Intervention Type: DRUG

Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle

Part 2: DLBCL G/R-CHOP

Participants with untreated DLBCL will receive G-CHOP or R-CHOP in Cycle 1, followed by G/R-CHOP + glofitamab for subsequent cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6 (up to 8). The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I.

Group Type: EXPERIMENTAL

Glofitamab

Intervention Type: DRUG

Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards.

Obinutuzumab (G)

Intervention Type: DRUG

Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only

Rituximab (R)

Intervention Type: DRUG

Rituximab will be administered as an IV infusion at a dose of 375 mg/m\^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP).

Tocilizumab

Intervention Type: DRUG

Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide 750 mg/m\^2 administered IV on Day 1 of each 21-day cycle

Doxorubicin

Intervention Type: DRUG

Doxorubicin 50 mg/m\^2 administered IV on Day 1 of each 21-day cycle

Vincristine

Intervention Type: DRUG

Vincristine 1.4 mg/m\^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg

Prednisone

Intervention Type: DRUG

Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle

Part 2: DLBCL Pola-R-CHP

Participants with untreated DLBCL will receive Pola-R-CHP + glofitamab on Day 1 of each 21-day cycle for a maximum of 6 cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I.

Group Type: EXPERIMENTAL

Glofitamab

Intervention Type: DRUG

Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards.

Rituximab (R)

Intervention Type: DRUG

Rituximab will be administered as an IV infusion at a dose of 375 mg/m\^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP).

Tocilizumab

Intervention Type: DRUG

Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide 750 mg/m\^2 administered IV on Day 1 of each 21-day cycle

Doxorubicin

Intervention Type: DRUG

Doxorubicin 50 mg/m\^2 administered IV on Day 1 of each 21-day cycle

Prednisone

Intervention Type: DRUG

Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle

Polatuzumab vedotin

Intervention Type: DRUG

Polatuzumab vedotin 1.8 mg/kg administered IV on Day 1 of each 21-day cycle

Interventions

Glofitamab

Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards.

Intervention Type: DRUG

Obinutuzumab (G)

Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only

Intervention Type: DRUG

Rituximab (R)

Rituximab will be administered as an IV infusion at a dose of 375 mg/m\^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP).

Intervention Type: DRUG

Tocilizumab

Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide 750 mg/m\^2 administered IV on Day 1 of each 21-day cycle

Intervention Type: DRUG

Doxorubicin

Doxorubicin 50 mg/m\^2 administered IV on Day 1 of each 21-day cycle

Intervention Type: DRUG

Vincristine

Vincristine 1.4 mg/m\^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg

Intervention Type: DRUG

Prednisone

Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle

Intervention Type: DRUG

Polatuzumab vedotin

Polatuzumab vedotin 1.8 mg/kg administered IV on Day 1 of each 21-day cycle

Intervention Type: DRUG

Other Intervention Names

RO7082859; Gazyva; Rituxan; Actemra; Oncovin

Eligibility Criteria

Inclusion Criteria

• Age >/=18 years
• For Part I r/r NHL dose-escalation, and Part II r/r NHL expansion: Histologically-confirmed NHL that is expected to express CD20, and which has relapsed/progressed following at least one prior treatment regimen containing R or G. Participants must be appropriate for treatment with CHOP and typically should not have been exposed to prior anthracyclines or must not exceed the cumulative lifetime dose of anthracyclines
• For Part II untreated DLBCL expansion: Histologically confirmed previously-untreated DLBCL that is expected to express CD20
• Able to provide a pretreatment biopsy between the final dose of last prior therapy and initiation of study medication at Cycle 1/Day 1
• Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as >1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as >1.0 cm in its longest dimension.
• Participants must have at least one measurable target lesion (> or = 1.5 cm) in its largest dimension by computed tomography (CT) scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for participants with r/r NHL; ECOG performance status 0-3 for participants with untreated DLBCL
• Life expectancy (in the opinion of the Investigator) of 18 weeks
• Adverse events (AEs) from prior anti-cancer therapy must have resolved to Grade </= 1
• Adequate liver function
• Adequate hematological function
• Adequate renal function
• Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection
• Negative test results for hepatitis C virus (HCV) and human immunodeficiency virus (HIV)

Exclusion Criteria

• Inability to comply with protocol mandated hospitalization and restrictions
• Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral (including, but not limited to Epstein Barr virus (EBV), cytomegalovirus (CMV), HBV, HCV, and HIV), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics, this pertains to completion of last course of antibiotic treatment) within 4 weeks of dosing
• Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radioimmuno-conjugates, antibody-drug conjugates, immune/cytokines, and monoclonal antibodies (e.g., anti-CTLA4, anti-PD1, and anti-PDL1) within 4 weeks or five half-lives of the drug, whichever is shorter, before G- or R-CHOP or Pola-R-CHP infusion on Cycle 1/Day 1
• Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease (only for participants treated in the polatuzumab vedotin arm)
• History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents, as follows: Grade >/=3 AEs, with the exception of Grade 3 endocrinopathy managed with replacement therapy; Grade 1-2 AEs that did not resolve to baseline after treatment completion
• Contraindication to any of the individual components of the immunochemotherapy
• Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent within 4 weeks prior to study treatment at Cycle 1/Day 1 infusion
• Prior solid organ transplantation
• Prior allogeneic stem cell transplantation
• Autologous stem cell transplantation within 100 days prior to Cycle 1/Day 1
• Prior treatment with CAR T-cell therapy within 30 days prior to study treatment at Cycle 1 Day 1
• History of autoimmune disease
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
• A history of confirmed progressive multifocal leukoencephalopathy
• Current or past history of central nervous system (CNS) lymphoma
• Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Participants who received corticosteroid treatment with </=30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to Cycle 1/Day 1. Participants may have received a brief (<7 days) course of systemic steroids (</=100 mg prednisone equivalent per day) prior to initiation of study therapy for control of lymphoma-related symptoms
• Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders (bronchospasm, obstructive pulmonary disease), and known autoimmune diseases
• Major surgery or significant traumatic injury < 28 days prior to the study treatment infusion at Cycle 1/Day 1 (excluding biopsies) or anticipation of the need for major surgery during study treatment
• Participants with another invasive malignancy that could affect compliance with the protocol or interpretation of results
• Significant or extensive cardiovascular disease
• Left ventricular ejection fraction < 50%
• Administration of a live, attenuated vaccine within 4 weeks before study treatment infusion on Cycle 1 Day 1 or anticipation that such a live, attenuated vaccine will be required during the study
• History of illicit drug or alcohol abuse within 12 months prior to screening, in the Investigator's judgment
• Any other diseases, metabolic dysfunction, physical examination finding (including mental status), or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
• Participants with latent or active tuberculosis

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

University of Alabama Medical Center

Birmingham, Alabama, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Fox Chase-Temple Cancer Center

Philadelphia, Pennsylvania, United States

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Rigshospitalet

København Ø, , Denmark

Hopital Claude Huriez

Lille, , France

Hopital Hotel Dieu Et Hme

Nantes, , France

Centre Henri Becquerel

Rouen, , France

Universitätsklinikum Erlangen, Translational Research Center (TRC), Medizin 5

Erlangen, , Germany

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

Istituto Nazionale Tumori Irccs Fondazione g. Pascale

Napoli, Campania, Italy

UO Ematologia, Ospedale S.Maria delle Croci

Ravenna, Emilia-Romagna, Italy

Asst Papa Giovanni Xxiii

Bergamo, Lombardy, Italy

Istituto Clinico Humanitas

Rozzano, Lombardy, Italy

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clínic i Provincial

Barcelona, , Spain

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, , Spain

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Nottingham University Hospitals NHS Trust - City Hospital

Nottingham, , United Kingdom

Countries

United States; Australia; Canada; Denmark; France; Germany; Italy; Spain; United Kingdom

References

Sam J, Leclercq-Cohen G, Gebhardt S, Surowka M, Herter S, Lechner K, Relf J, Briner S, Varol A, Appelt B, Domocos I, Nicolini VG, Bez M, Bommer E, Jenni S, Schoenle A, Le Clech M, Colombetti S, Klein C, Umana P, Lundberg P, Korfi K, Bottos A, Bacac M. Preclinical advances in glofitamab combinations: a new frontier for non-Hodgkin lymphoma. Blood. 2025 Aug 1:blood.2025028863. doi: 10.1182/blood.2025028863. Online ahead of print.

Reference Type: DERIVED

PMID: 40749164 (View on PubMed)

Other Identifiers

2017-003648-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NP40126

Identifier Type: -

Identifier Source: org_study_id