A Study to Evaluate the Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Englumafusp Alfa in Combination With Obinutuzumab and in Combination With Glofitamab Following a Pre-Treatment Dose of Obinutuzumab in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

NCT ID: NCT04077723

Last Updated: 2026-01-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

498 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-13

Study Completion Date

2027-03-31

Brief Summary

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This is a phase I/II, open-label, dose-escalation study designed to evaluate the safety, tolerability, and efficacy of englumafusp alfa (RO7227166) in participants with relapsed/refractory Non-Hodgkin's Lymphoma (r/r NHL). Englumafusp alfa will be administered by intravenous (IV) infusion in combination with obinutuzumab and in combination with glofitamab. A fixed dose of obinutuzumab (Gpt; pre-treatment) will be administered up to seven days prior to the first administration of englumafusp alfa and seven days prior to the first administration of glofitamab. This entry-into-human study is divided into a dose-escalation stage (Part I and Part II) and a dose expansion stage (Part III).

Detailed Description

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Conditions

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Lymphoma, Non-Hodgkin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part I

Combination Dose-Escalation: Mixed r/r NHL participants will receive a fixed dose of obinutuzumab up to seven days prior to first administration of englumafusp alfa. Englumafusp alfa will be administered by intravenous (IV) infusion in combination with obinutuzumab in a three-weekly schedule (Q3W).

Group Type EXPERIMENTAL

Englumafusp alfa

Intervention Type DRUG

Englumafusp alfa will be administered by intravenous (IV) infusion three-weekly (Q3W) in combination with a fixed dose of obinutuzumab (Part I) and in combination with a fixed dose of glofitamab (Part II and Part III).

Obinutuzumab

Intervention Type DRUG

A fixed dose of obinutuzumab will be administered up to 7 days prior to the first dose of englumafusp alfa, then in combination with obinutuzumab Q3W (Part I).

A fixed dose of obinutuzumab will be administered up to 7 days prior to the first dose of englumafusp alfa or between Day -3 and -7 (Part II and Part III).

Tocilizumab

Intervention Type DRUG

Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).

Part II

Combination Dose-Escalation: Mixed r/r participants and participants with mixed r/r mantle cell lymphoma (MCL) and Richters transformation will receive a fixed dose of obinutuzumab seven days prior to first administration of englumafusp alfa. Englumafusp alfa will be administered by IV infusion in combination with glofitamab in a three-weekly schedule (Q3W).

Group Type EXPERIMENTAL

Englumafusp alfa

Intervention Type DRUG

Englumafusp alfa will be administered by intravenous (IV) infusion three-weekly (Q3W) in combination with a fixed dose of obinutuzumab (Part I) and in combination with a fixed dose of glofitamab (Part II and Part III).

Obinutuzumab

Intervention Type DRUG

A fixed dose of obinutuzumab will be administered up to 7 days prior to the first dose of englumafusp alfa, then in combination with obinutuzumab Q3W (Part I).

A fixed dose of obinutuzumab will be administered up to 7 days prior to the first dose of englumafusp alfa or between Day -3 and -7 (Part II and Part III).

Glofitamab

Intervention Type DRUG

A fixed dose of glofitamab will be administered Q3W in combination with englumafusp alfa in Part II and Part III

Tocilizumab

Intervention Type DRUG

Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).

Part III

Dose-Expansion Stage: Participants with r/r diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS), high-grade B-cell lymphoma (HGBCL), primary mediastinal B-cell lymphoma (PMBCL), and DLBCL arising from FL (transformed FL) will receive englumafusp alfa administered by IV infusion in combination with glofitamab in a three-weekly schedule (Q3W).

Group Type EXPERIMENTAL

Englumafusp alfa

Intervention Type DRUG

Englumafusp alfa will be administered by intravenous (IV) infusion three-weekly (Q3W) in combination with a fixed dose of obinutuzumab (Part I) and in combination with a fixed dose of glofitamab (Part II and Part III).

Obinutuzumab

Intervention Type DRUG

A fixed dose of obinutuzumab will be administered up to 7 days prior to the first dose of englumafusp alfa, then in combination with obinutuzumab Q3W (Part I).

A fixed dose of obinutuzumab will be administered up to 7 days prior to the first dose of englumafusp alfa or between Day -3 and -7 (Part II and Part III).

Glofitamab

Intervention Type DRUG

A fixed dose of glofitamab will be administered Q3W in combination with englumafusp alfa in Part II and Part III

Tocilizumab

Intervention Type DRUG

Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).

Interventions

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Englumafusp alfa

Englumafusp alfa will be administered by intravenous (IV) infusion three-weekly (Q3W) in combination with a fixed dose of obinutuzumab (Part I) and in combination with a fixed dose of glofitamab (Part II and Part III).

Intervention Type DRUG

Obinutuzumab

A fixed dose of obinutuzumab will be administered up to 7 days prior to the first dose of englumafusp alfa, then in combination with obinutuzumab Q3W (Part I).

A fixed dose of obinutuzumab will be administered up to 7 days prior to the first dose of englumafusp alfa or between Day -3 and -7 (Part II and Part III).

Intervention Type DRUG

Glofitamab

A fixed dose of glofitamab will be administered Q3W in combination with englumafusp alfa in Part II and Part III

Intervention Type DRUG

Tocilizumab

Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).

Intervention Type DRUG

Other Intervention Names

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A CD19 Targeted 4-1BB Ligand; RO7227166 Gpt, RO5072759, Gazyva, Gazyvaro CD20-TCB, RO7082859 Actemra, RoActemra

Eligibility Criteria

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Inclusion Criteria

* History or status of a histologically-confirmed hematological malignancy that is expected to express CD19 and CD20; relapse after or failure to respond to at least one prior treatment regimen; no available treatment options that are expected to prolong survival (Part I and II); relapsed after or failed to respond to only one prior systemic treatment regimen (Part III)
* Must have at least one measurable target lesion (\>/= 1.5 cm) in its largest dimension by computed tomography scan
* Able and willing to provide a fresh biopsy from a safely accessible site, per Investigator's determination, providing the participant has more than one measurable target lesion
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, or \</= 2 for some participants in Part III
* Life expectancy of \>/= 12 weeks
* Adverse events from prior anti-cancer therapy must have resolved to Grade \</= 1
* Adequate liver, hematological, and renal function
* Negative test results for acute or chronic hepatitis B virus infection
* Negative test results for hepatitis C virus and HIV
* The contraception and abstinence requirements are intended to prevent exposure of an embryo to the study treatment. The reliability of sexual abstinence for male and/or female enrollment eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of preventing drug exposure
* Female participants: A female participant is eligible to participate if she is not pregnant and not breastfeeding, and if at least one of the following applies: women of non-childbearing potential (WONCBP); women of child bearing potential (WOCBP) who agree to remain abstinent or use two highly effective contraceptive methods with a failure rate of \<1% per year during the treatment period and for at least 18 months after obinutuzumab or 3.5 months after the last dose of englumafusp alfa, 2 months after last dose of glofitamab, or 3 months after the last dose of tocilizumab, whichever is longer. Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal occlusion/ ligation, male sexual partner who is sterilized, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method; have a negative pregnancy test (blood) within the 7 days prior to the first study treatment administration
* Male participants: During the treatment period and for at least 3 months after obinutuzumab, or 3.5 months after the last dose of englumafusp alfa, 2 months after the last dose of glofitamab, or 2 months after the last dose of tocilizumab whichever is longer, agreement to: Remain abstinent or use contraceptive measures such as a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year, with a partner who is a women of childbearing potential. With pregnant female partner, remain abstinent or use contraceptive measures such as a condom to avoid exposing the embryo; refrain from donating sperm during this same period

Exclusion Criteria

* Circulating lymphoma cells, defined by out of range (high) absolute lymphocyte count (ALC) or the presence of abnormal cells in the peripheral blood signifying circulating lymphoma cells (for some participants in Part III, ALC only)
* 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 (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics
* Pregnant or breast-feeding or intending to become pregnant during the study
* Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines or monoclonal antibodies within 4 weeks or five half-lives of the drug, whichever is shorter, before obinutuzumab infusion
* History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents and auto-immune disease
* Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational or approved anti-cancer agent within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to obinutuzumab infusion
* Prior solid organ transplantation
* Prior allogeneic stem cell transplant
* Autologous stem cell transplant within 100 days prior to obinutuzumab infusion
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy and confirmed progressive multifocal leukoencephalopathy
* Current or past history of central nervous system (CNS) lymphoma and CNS 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 and known autoimmune diseases
* Major surgery or significant traumatic injury \< 28 days prior to the Gpt infusion or anticipation of the need for major surgery during study treatment
* Participants with another invasive malignancy in the last 2 years
* Significant cardiovascular disease
* Administration of a live, attenuated vaccine within 4 weeks before Gpt infusion or anticipation that such a live attenuated vaccine will be required during the study
* Received systemic immunosuppressive medications (including but not limited to cyclohosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within two weeks prior to Gpt, with the exception of corticosteroid treatment \<=25 mg/day of prednisone or equivalent, however there must be documentation that the participant was on a stable dose of at least a 2-week duration prior to Gpt infusion. Inhaled and topical steroids are permitted
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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City of Hope Medical Center

Pasadena, California, United States

Site Status ACTIVE_NOT_RECRUITING

University of California San Francisco

San Francisco, California, United States

Site Status RECRUITING

Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center

Denver, Colorado, United States

Site Status RECRUITING

Beth Israel Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

MSKCC

New York, New York, United States

Site Status RECRUITING

OhioHealth Research Institute

Columbus, Ohio, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

South Austin Medical Center

Austin, Texas, United States

Site Status RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status RECRUITING

UZ Gent

Ghent, , Belgium

Site Status RECRUITING

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Site Status RECRUITING

Jewish General Hospital

Montreal, Quebec, Canada

Site Status RECRUITING

Beijing Cancer Hospital

Beijing, , China

Site Status RECRUITING

Shandong Cancer Hospital

Jinan, , China

Site Status RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, , China

Site Status RECRUITING

Aarhus Universitetshospital Skejby

Aarhus N, , Denmark

Site Status RECRUITING

Rigshospitalet

København Ø, , Denmark

Site Status RECRUITING

Odense Universitetshospital

Odense C, , Denmark

Site Status RECRUITING

CHRU de Lille

Lille, , France

Site Status RECRUITING

CHU Montpellier - Saint ELOI

Montpellier, , France

Site Status RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status RECRUITING

CHU DE RENNES - CHU Pontchaillou

Rennes, , France

Site Status RECRUITING

Istituto Nazionale Tumori Irccs Fondazione g. Pascale

Napoli, Campania, Italy

Site Status RECRUITING

Asst Papa Giovanni Xxiii

Bergamo, Lombardy, Italy

Site Status RECRUITING

Irccs Istituto Europeo Di Oncologia (IEO)

Milan, Lombardy, Italy

Site Status RECRUITING

Istituto Clinico Humanitas

Rozzano, Lombardy, Italy

Site Status RECRUITING

Auckland City Hospital, Cancer and Blood Research

Auckland, , New Zealand

Site Status RECRUITING

Waikato Hospital - Cancer and Blood Research Trials Unit

Hamilton, , New Zealand

Site Status RECRUITING

Pusan National University Hospital

Busan, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

Hospital Duran i Reynals L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status RECRUITING

Clinica Universitaria de Navarra

Pamplona, Navarre, Spain

Site Status RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Hospital Univ. 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Hospital Clinico Universitario Virgen de la Victoria

Málaga, , Spain

Site Status RECRUITING

The HOPE Clinical Trials Unit

Leicester, , United Kingdom

Site Status COMPLETED

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Belgium Canada China Denmark France Italy New Zealand South Korea Spain United Kingdom

Central Contacts

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Reference Study ID Number: BP41072 https://forpatients.roche.com/

Role: CONTACT

888-662-6728 (U.S. and Canada)

Other Identifiers

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2019-000416-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2022-502616-37-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

BP41072

Identifier Type: -

Identifier Source: org_study_id

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