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

NCT03467373 | Completed Phase 1 FDA Drug

• 2 other identifiers: NP401262017-003648-18
• Study Type: interventional
• Target: 111
• Locations: 9 countries
• Sites: 22

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

Outcome Measures

Primary Outcomes (2)

• Part I: Percentage of Participants with Dose Limiting Toxicities (DLTs)

  Up to 29 months

• Part I and II: Percentage of Participants with Adverse Events

  Up to 29 months

Secondary Outcomes (13)

• Parts I and II: Percentage of Participants with a Complete Response (CR) as Assessed by the Investigator using Modified Lugano 2014 Criteria

  Up to 29 months

• Parts I and II: Percentage of Participants with Overall Response (Partial Response [PR] or Complete Response [CR])

  Up to 29 months

• Parts I and II: Duration of Response (DOR)

  Up to 29 months

• Duration of CR

  Up to 29 months

• Progression-Free Survival (PFS)

  Up to 29 months

Study Arms (3)

Part 1: Dose Escalation r/r NHL

EXPERIMENTAL

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.

Drug: Glofitamab; Drug: Obinutuzumab (G); Drug: Rituximab (R); Drug: Tocilizumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone

Part 2: DLBCL G/R-CHOP

EXPERIMENTAL

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.

Drug: Glofitamab; Drug: Obinutuzumab (G); Drug: Rituximab (R); Drug: Tocilizumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone

Part 2: DLBCL Pola-R-CHP

EXPERIMENTAL

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.

Drug: Glofitamab; Drug: Rituximab (R); Drug: Tocilizumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Polatuzumab vedotin

Interventions

Glofitamab 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.

Also known as: RO7082859

Part 1: Dose Escalation r/r NHL; Part 2: DLBCL G/R-CHOP; Part 2: DLBCL Pola-R-CHP

Obinutuzumab (G) DRUG

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

Also known as: Gazyva

Part 1: Dose Escalation r/r NHL; Part 2: DLBCL G/R-CHOP

Rituximab (R) 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).

Also known as: Rituxan

Part 1: Dose Escalation r/r NHL; Part 2: DLBCL G/R-CHOP; Part 2: DLBCL Pola-R-CHP

Tocilizumab 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.

Also known as: Actemra

Part 1: Dose Escalation r/r NHL; Part 2: DLBCL G/R-CHOP; Part 2: DLBCL Pola-R-CHP

Cyclophosphamide DRUG

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

Part 1: Dose Escalation r/r NHL; Part 2: DLBCL G/R-CHOP; Part 2: DLBCL Pola-R-CHP

Doxorubicin DRUG

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

Part 1: Dose Escalation r/r NHL; Part 2: DLBCL G/R-CHOP; Part 2: DLBCL Pola-R-CHP

Vincristine 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

Also known as: Oncovin

Part 1: Dose Escalation r/r NHL; Part 2: DLBCL G/R-CHOP

Prednisone 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 1: Dose Escalation r/r NHL; Part 2: DLBCL G/R-CHOP; Part 2: DLBCL Pola-R-CHP

Polatuzumab vedotin DRUG

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

Part 2: DLBCL Pola-R-CHP

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (22)

University of Alabama Medical Center

Birmingham, Alabama, 35294, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Fox Chase-Temple Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

Location

Rigshospitalet

København Ø, 2100, Denmark

Location

Hopital Claude Huriez

Lille, 59037, France

Location

Hopital Hotel Dieu Et Hme

Nantes, 44093, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

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

Erlangen, 91054, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Istituto Nazionale Tumori Irccs Fondazione g. Pascale

Napoli, Campania, 80131, Italy

Location

UO Ematologia, Ospedale S.Maria delle Croci

Ravenna, Emilia-Romagna, 48121, Italy

Location

Asst Papa Giovanni Xxiii

Bergamo, Lombardy, 24127, Italy

Location

Istituto Clinico Humanitas

Rozzano, Lombardy, 20089, Italy

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic i Provincial

Barcelona, 08036, Spain

Location

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

University College London Hospitals NHS Foundation Trust

London, W1T 7HA, United Kingdom

Location

Nottingham University Hospitals NHS Trust - City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (1)

• Sam J, Leclercq-Cohen G, Gebhardt S, Surowka M, Herter S, Lechner K, Relf J, Briner S, Varol A, Appelt B, Domocos I, Nicolini V, 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 Oct 9;146(15):1824-1836. doi: 10.1182/blood.2025028863.

  PMID: 40749164 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Interventions

glofitamab; obinutuzumab; Rituximab; tocilizumab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; polatuzumab vedotin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: March 16, 2018
• Study Start: March 13, 2018
• Primary Completion: December 2, 2024
• Study Completion: December 2, 2024
• Last Updated: January 17, 2025

Record last verified: 2025-01

Locations

FR (3); ES (3); CA (1); DK (1); AU (1); DE (4); US (3); GB (2); IT (4)