A Dose Escalation Study of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab, Administered After a Fixed, Single Pre-treatment Dose of Obinutuzumab in Participants With Relapsed/Refractory B-cell Non-hodgkin's Lymphoma

NCT03075696 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: NP301792016-001185-282023-505625-14-00
• Study Type: interventional
• Target: 940
• Locations: 13 countries
• Sites: 34

Brief Summary

This is a Phase I/II, multicenter, open-label, dose-escalation study designed to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of a novel T-Cell bispecific (TCB), glofitamab, administered by intravenous (IV) infusion as a single agent and in combination with obinutuzumab, following pre-treatment with a one-time, fixed dose of obinutuzumab. This entry-into-human (EIH) study is divided in 3 parts: dose escalation (Parts I and II) and dose expansion (Part III). Single-participant dose-escalation cohorts will be used in Part I, followed by conversion to multiple participant dose-escalation cohorts (Part II), in order to define a tentative maximum tolerated dose (MTD) or optimal biological dose (OBD). The expansion cohorts (Part III) will be initiated when the tentative MTD/OBD is defined, to further evaluate the safety, PK and therapeutic activity of glofitamab.

Conditions

Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (11)

• Part I and II: Percentage of Participants With Dose Limiting Toxicities (DLTs)

  From Baseline up to 4 weeks

• Part I, II and III: Percentage of Participants With Adverse Events (AEs)

  From Baseline up to 90 days after last dose of study drug or until study completion or participant withdrawal (up to 5 years)

• Part II: MTD or OBD of Glofitamab

  From Baseline up to 4 weeks

• Part II: Recommended Phase II Dose (RP2D) of Glofitamab

  From Baseline up to 5 years

• Part III: Complete Response (CR) Rate as Assessed by Independent Review Committee (IRC) According to Standard Non-hodgkin's Lymphoma (NHL) Response Criteria (Lugano Classification)

  From treatment start up to 5 years

• Part I, II and III: Area Under the Serum Concentration Versus Time Curve (AUC) of Glofitamab

  At pre-defined intervals from Cycle 1 Day 1 to Day 71

• Part I, II and III: Maximum Serum Concentration (Cmax) of Glofitamab

  At pre-defined intervals from Cycle 1 Day 1 to Day 198

• Part I, II and III: Minimum Serum Concentration (Cmin) of Glofitamab

  At pre-defined intervals from Cycle 1 Day 1 up to Day 198

• Part I, II and III: Clearance (CL) of Glofitamab

  At pre-defined intervals from Cycle 1 Day 1 to Day 71

• Part I, II and III: Volume of Distribution at Steady-state (Vss) of Glofitamab

  At pre-defined intervals from Cycle 1 Day 1 to Day 71

• Part I, II and III: Half-life (t1/2) of Glofitamab

  At pre-defined intervals from Cycle 1 Day 1 to Day 71

Secondary Outcomes (13)

• Part I, II and III: Cmax of Obinutuzumab

  Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of glofitamab on Day 1 of Cycle 1

• Part I, II and III: Cmin of Obinutuzumab

  Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of glofitamab on Day 1 of Cycle 1

• Part I, II and III: Anti-drug Antibodies (ADA) to Glofitamab

  Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of glofitamab on Day 1 of each cycle from Cycle 2 onwards for a maximum of 8-12 cycles, and at EOT/follow-up visit (up to 5 years)

• Parts I and II: Percentage of Participants With Overall Response (Partial Response [PR] or Complete Response [CR]) as Determined by the Lugano Classification

  From Baseline up to end of study or discontinuation due to disease progression (up to 5 years)

• Part I, II and III: Percentage of Participants With PR or CR (Overall Response Rate [ORR]) as Determined by the Lugano Classifications

  From Baseline up to end of study or discontinuation due to disease progression (up to 5 years)

Study Arms (3)

Part I: Dose Escalation

EXPERIMENTAL

Participants (single participant cohorts) will receive obinutuzumab pretreatment (Gpt) 1000 milligrams (mg) single dose IV infusion on Day -7 followed by glofitamab IV infusion on Day 1 and Day 8 of Cycle 1. From Cycle 2 onwards, ascending doses of glofitamab will be administered on Day 1 of every 2 week (Q2W) cycle up to Cycle 12 (24 weeks) or until unacceptable toxicity or disease progression. Glofitamab dosing will be initiated at 5 micrograms (mcg) (flat dose) followed by doses of 15 mcg, 45 mcg, 135 mcg, 405 mcg and 810 mcg.

Drug: Glofitamab; Drug: Obinutuzumab; Drug: Tocilizumab

Part II: Dose Escalation

EXPERIMENTAL

In each treatment regimen, participants will receive Gpt 1000 mg IV infusion on Day -7; or 2000 mg either administered on Day -7, or split into two 1000 mg doses on Days -1 and -7. The first glofitamab IV infusion will be given on Day 1 of Cycle 1 and a total of 12 cycles will be administered. Monotherapy, glofitamab as a single agent: ascending doses of glofitamab administered on Day 1 of Q2W or every 3 week (Q3W) cycle until either the MTD/OBD is defined. Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with ascending doses of glofitamab on Day 1 of Q3W cycle until either the MTD/OBD is defined. Step-up dosing: Q3W, participants will receive an initial low dose of glofitamab on Cycle 1 Day 1, followed by a higher dose on Cycle 1 Day 8; the total dose in Cycle 1 will not exceed the previously determined MTD. Higher doses may be explored from Cycle 2 or later cycles.

Drug: Glofitamab; Drug: Obinutuzumab; Drug: Tocilizumab

Part III: Dose Expansion

EXPERIMENTAL

Part III will start once MTD/OBD is defined. Participants will receive Gpt 1000 mg single dose IV infusion on Day -7, followed by glofitamab at a fixed dose regimen or step-up dose regimen on a Q2W or Q3W dosing schedule as determined in Part II. A total of 12 cycles will be administered. Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with glofitamab at the dosing regimen determined in Part II.

Drug: Glofitamab; Drug: Obinutuzumab; Drug: Tocilizumab

Interventions

Glofitamab DRUG

Glofitamab will be administered at a dose and as per the schedule specified in the respective arms.

Also known as: RO7082859

Part I: Dose Escalation; Part II: Dose Escalation; Part III: Dose Expansion

Obinutuzumab DRUG

Obinutuzumab 1000 mg single dose IV infusion on Day -7; or 2000 mg single dose administered on Day -7, or split into two 1000 mg doses administered on Days -1 and -7, and per the schedule specified in the respective arms.

Also known as: RO5072759, GA101, Gazyva®, Gazyvaro™

Part I: Dose Escalation; Part II: Dose Escalation; Part III: Dose Expansion

Tocilizumab DRUG

Tocilizumab will be administered as an IV infusion, if required, for the management of severe Cytokine Release Syndrome (CRS) occurring during or after any infusion of glofitamab, as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents.

Also known as: Actemra®, Roactemra®

Part I: Dose Escalation; Part II: Dose Escalation; Part III: Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Depending upon study part, a history or status of: 1) a histologically-confirmed hematological malignancy that is expected to express cluster of differentiation (CD)20; 2) relapse after or failure to respond to at least one prior treatment regimen; and 3) no available treatment options that are expected to prolong survival (e.g., standard chemotherapy or autologous stem cell transplant \[ASCT\])
• 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
• Able to provide a tumor tissue pretreatment biopsy at last relapse or during screening from a safely accessible site, per investigator determination, providing the patient has more than one measurable target lesion
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of \>/=12 weeks
• AEs from prior anti-cancer therapy must have resolved to Grade less than or equal to (\</=) 1
• Adequate liver, hematological and 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)
• Negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential. Women who are not of childbearing potential who are considered to be post-menopausal (at least 12 months of non-therapy amenorrhea) or surgically sterile (absence of ovaries and/or uterus) are not required to have a pregnancy test

You may not qualify if:

• Inability to comply with protocol mandated hospitalizations and restrictions
• Participants with chronic lymphocytic leukemia (CLL), Burkitt lymphoma and lymphoplasmacytic lymphoma
• Participants with a known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Participants with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to obinutuzumab infusion or by clinical judgment in the absence of a positive blood culture
• Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing
• Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (e.g., anti-cytotoxic T-lymphocyte-associated protein 4 \[anti-CTLA4\], anti-programmed death 1 \[anti-PD1\] and anti-programmed death ligand 1 \[anti-PDL1\]) within 4 weeks or five half-lives of the drug, whichever is shorter, before obinutuzumab infusion on Cycle 1 Day -7
• History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents
• Documented refractoriness to an obinutuzumab-containing regimen
• Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent, including chimeric antigen receptor therapy (CAR-T) within 4 weeks prior to obinutuzumab infusion
• Prior solid organ transplantation
• Prior allogeneic stem cell transplantation (SCT)
• Autologous SCT within 100 days prior to obinutuzumab infusion
• Participant with history of confirmed progressive multifocal leukoencephalopathy (PML)
• Current or past history of central nervous system (CNS) lymphoma
• Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Participants with a past history of stroke that have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits are allowed

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (34)

University of Michigan

Ann Arbor, Michigan, 48109-0934, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

MSKCC

New York, New York, 10065, United States

Location

Allegheny Health Network (Pittsburg PA)

Pittsburgh, Pennsylvania, 15212, United States

Location

Swedish Cancer Inst.

Seattle, Washington, 98104, United States

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

Location

Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK

Prague, 128 08, Czechia

Location

Rigshospitalet

København Ø, 2100, Denmark

Location

Helsinki University Central Hospital

Helsinki, 00029, Finland

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Hopital Claude Huriez

Lille, 59037, France

Location

CHU Saint Eloi

Montpellier, 34295, France

Location

Ch Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU DE RENNES - CHU Pontchaillou

Rennes, 35033, France

Location

AUSL della Romagna

Ravenna, Emilia-Romagna, 48121, Italy

Location

Fond. IRCCS Istituto Nazionale Tumori

Milan, Lombardy, 20133, Italy

Location

Istituto Clinico Humanitas

Rozzano, Lombardy, 20089, Italy

Location

Auckland Cancer Trial Centre

Auckland, 1023, New Zealand

Location

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214, Poland

Location

Uniwersytecki Szpital Kliniczny w Poznaniu

Późna, 60-569, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroc?aw, 50-367, Poland

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08915, Spain

Location

Hospital Duran i Reynals L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Univ. 12 de Octubre

Madrid, 28041, Spain

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

National Taiwan Universtiy Hospital

Taipei, 100, Taiwan

Location

Related Publications (5)

• Phillips TJ, Carlo-Stella C, Morschhauser F, Bachy E, Crump M, Trneny M, Bartlett NL, Zaucha J, Wrobel T, Offner F, Humphrey K, Relf J, Filezac de L'Etang A, Carlile DJ, Byrne B, Qayum N, Lundberg L, Dickinson M. Glofitamab in Relapsed/Refractory Mantle Cell Lymphoma: Results From a Phase I/II Study. J Clin Oncol. 2025 Jan 20;43(3):318-328. doi: 10.1200/JCO.23.02470. Epub 2024 Oct 4.

  PMID: 39365960 DERIVED

• Dickinson MJ, Carlo-Stella C, Morschhauser F, Bachy E, Corradini P, Iacoboni G, Khan C, Wrobel T, Offner F, Trneny M, Wu SJ, Cartron G, Hertzberg M, Sureda A, Perez-Callejo D, Lundberg L, Relf J, Dixon M, Clark E, Humphrey K, Hutchings M. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Dec 15;387(24):2220-2231. doi: 10.1056/NEJMoa2206913. Epub 2022 Dec 11.

  PMID: 36507690 DERIVED

• Frances N, Bacac M, Bray-French K, Christen F, Hinton H, Husar E, Quackenbush E, Schafer M, Schick E, Vyver AV, Richter WF. Novel in Vivo and in Vitro Pharmacokinetic/Pharmacodynamic-Based Human Starting Dose Selection for Glofitamab. J Pharm Sci. 2022 Apr;111(4):1208-1218. doi: 10.1016/j.xphs.2021.12.019. Epub 2021 Dec 22.

  PMID: 34953862 DERIVED

• Broske AE, Korfi K, Belousov A, Wilson S, Ooi CH, Bolen CR, Canamero M, Alcaide EG, James I, Piccione EC, Carlile DJ, Dimier N, Umana P, Bacac M, Weisser M, Dickinson M. Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma. Blood Adv. 2022 Feb 8;6(3):1025-1037. doi: 10.1182/bloodadvances.2021005954.

  PMID: 34941996 DERIVED

• Hutchings M, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC, Sureda A, Salles G, Martinez-Lopez J, Crump M, Thomas DN, Morcos PN, Ferlini C, Broske AE, Belousov A, Bacac M, Dimier N, Carlile DJ, Lundberg L, Perez-Callejo D, Umana P, Moore T, Weisser M, Dickinson MJ. Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. J Clin Oncol. 2021 Jun 20;39(18):1959-1970. doi: 10.1200/JCO.20.03175. Epub 2021 Mar 19.

  PMID: 33739857 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

glofitamab; obinutuzumab; tocilizumab

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2017
• First Posted: March 9, 2017
• Study Start: February 21, 2017
• Primary Completion (Estimated): March 30, 2029
• Study Completion (Estimated): March 30, 2029
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

IT (3); ES (6); PL (3); NZ (1); BE (2); DK (1); TW (2); CA (1); US (6); FI (1); FR (5); AU (2); CZ (1)