Lymphoma, Non-HodgkinPhase 1/2NCT04077723
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
A Phase 1/2 study testing Englumafusp alfa, Obinutuzumab and Glofitamab in people with Lymphoma, Non-Hodgkin, run by Hoffmann-La Roche at 35 sites in 12 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Non-Hodgkin
- What is being tested?
- Englumafusp alfa, Obinutuzumab and Glofitamab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 498 participants
- Where
- 35 sitesin 12 countries
- Study dates
- 13 Aug 2019to 31 Mar 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
35 sites in 12 countries.
35 sites in 12 countries
United States4 sites
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4009
City of Hope Medical Center
Pasadena, California, 91105
University of California San Francisco
San Francisco, California, 94158
Washington University School of Medicine
St Louis, Missouri, 63110
China4 sites
Beijing Cancer Hospital
Beijing, 100142
Shandong Cancer Hospital
Jinan, 250117
Fudan University Shanghai Cancer Center
Shanghai, 201315
The First Affiliated Hospital of Xiamen University
Xiamen, 361003
France4 sites
CHRU de Lille
Lille, 59037
CHU Montpellier - Saint ELOI
Montpellier, 34295
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
CHU DE RENNES - CHU Pontchaillou
Rennes, 35033
Italy4 sites
Asst Papa Giovanni Xxiii
Bergamo, Lombardy, 24127
Irccs Istituto Europeo Di Oncologia (IEO)
Milan, Lombardy, 20141
Istituto Nazionale Tumori Irccs Fondazione g. Pascale
Naples, Campania, 80131
Istituto Clinico Humanitas
Rozzano, Lombardy, 20089
South Korea4 sites
Pusan National University Hospital
Busan, 49241
Seoul National University Hospital
Seoul, 03080
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Denmark3 sites
Aarhus Universitetshospital Skejby
Aarhus N, 8200
Rigshospitalet
København Ø, 2100
Odense Universitetshospital
Odense C, 5000
Spain3 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Univ. 12 de Octubre
Madrid, 28041
Hospital Clinico Universitario Virgen de la Victoria
Málaga, 29010
Australia2 sites
Peter Maccallum Cancer Centre
Melbourne, Victoria, 3000
The Alfred Hospital
Melbourne, Victoria, 3004
Canada2 sites
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, B3H 2Y9
Jewish General Hospital
Montreal, Quebec, H3T 1E2
New Zealand2 sites
Auckland City Hospital, Cancer and Blood Research
Auckland, 1023
Waikato Hospital - Cancer and Blood Research Trials Unit
Hamilton, 3204
United Kingdom2 sites
The HOPE Clinical Trials Unit
Leicester, LE1 5WW
University College London Hospitals NHS Foundation Trust
London, W1T 7HA
About this study
Official title: An Open-Label, Phase I/II Study to Evaluate the Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Englumafusp Alfa (RO7227166, A CD19 Targeted 4-1BB Ligand) in Combination With Obinutuzumab and in Combination With Glofitamab Following a Pre-treatment Dose of Obinutuzumab Administered in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
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).
- Conditions
- Lymphoma, Non-Hodgkin
- Being tested
- Englumafusp alfa, Obinutuzumab, Glofitamab, Tocilizumab
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Englumafusp alfaDrug
Also called A CD19 Targeted 4-1BB Ligand; RO7227166
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).
ObinutuzumabDrug
Also called Gpt, RO5072759, Gazyva, Gazyvaro
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).
GlofitamabDrug
Also called CD20-TCB, RO7082859
A fixed dose of glofitamab will be administered Q3W in combination with englumafusp alfa in Part II and Part III
TocilizumabDrug
Also called Actemra, RoActemra
Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).
| Study group | Role | What they receive |
|---|---|---|
| Part I | Experimental | 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). Receives: Drug: Englumafusp alfa; Drug: Obinutuzumab; Drug: Tocilizumab |
| Part II | Experimental | 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). Receives: Drug: Englumafusp alfa; Drug: Obinutuzumab; Drug: Glofitamab; Drug: Tocilizumab |
| Part III | Experimental | 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). Receives: Drug: Englumafusp alfa; Drug: Obinutuzumab; Drug: Glofitamab; Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nature and frequency of dose-limiting toxicities (DLTs)
Measured: 28 days in Part I and Part II
Proportion of Participants with Adverse Event (AE)
Incidence, nature, and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Measured: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Overall Response Rate (ORR)
Measured: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Disease Control Rate (DCR)
Measured: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Duration of Response (DOR)
Measured: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Progression-free Survival (PFS)
Measured: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Overall Survival (OS)
Measured: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Complete Response (CR)
Measured: Part III: Up to 9 months or up to 18 months
Secondary outcomes (24)
Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with obinutuzumab and glofitamab
Measured: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with obinutuzumab and glofitamab
Measured: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with obinutuzumab and glofitamab
Measured: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Clearance (CL) of englumafusp alfa in combination with obinutuzumab and glofitamab
Measured: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Volume of distribution of steady state (Vss) and half-life (t1/2) of englumafusp alfa in combination with obinutuzumab and glofitamab
Measured: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
ORR
Measured: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
DCR
Measured: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
DOR
Measured: After end of Study approximately every 3 months until death, loss to follow-up or study termination
PFS
Measured: After end of Study approximately every 3 months until death, loss to follow-up or study termination
OS
Measured: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Proportion of Participants with Adverse Event (AE)
Incidence, nature, and severity of AEs graded according to the NCI CTCAE v5.0
Measured: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with glofitamab
Measured: Part III: Up to 9 months or up to 18 months
Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with glofitamab
Measured: Part III: Up to 9 months or up to 18 months
Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with glofitamab
Measured: Part III: Up to 9 months or up to 18 months
Clearance (CL) of englumafusp alfa in combination with glofitamab
Measured: Part III: Up to 9 months or up to 18 months
Volume of distribution of steady state (Vss) and half-life (t1/2) of englumafusp alfa in combination with glofitamab Part I/II/III
Measured: Part III: Up to 9 months or up to 18 months
T-cell and Natural killer (NK)-cell status in blood, using markers of T and NK-cell lineage, function and activation including, but not limited to, CD3, CD8, 41BB, and Ki67 expression
Measured: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
B-cell reduction in blood and tumor tissue
Measured: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Change from Baseline in englumafusp alfa Anti-Drug Antibody (ADA) Titer
Measured: Part 1: Up to 24 months; Part ll/lll: Up to 18 months
Time to First Complete Response (TFCR)
Measured: Up to 18 months
Time to First Overall Response (TFOR)
Measured: Up to 18 months
Duration of Complete Response (DOCR)
Measured: Part III: Up to 9 months or up to 18 months
Change from Baseline in Physical Function, Role Function, and Health-Related Quality of Life (HRQoL) Based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Measured: Part III: Up to 9 months or up to 18 months
Change from Baseline in Physical Function, Role Function, and HRQoL According to the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Scale
Measured: Part III: Up to 9 months or up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2019
- Study start13 Aug 2019
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, Non-HodgkinStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 498 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04077723
- Sponsor's protocol ID
- BP41072
- Other IDs
- 2019-000416-28, 2022-502616-37-00, 2019
- Status last verified
- Aug 2026
- First submitted
- 9 Aug 2019
- Last updated
- 27 Aug 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
Publications
Hutchings M, Dickinson M, Gritti G, Carlo-Stella C, Townsend W, Bosch F, Bartlett NL, Cartron G, Ghesquieres H, Houot R, Walter H, Offner F, Dimier N, Jamois C, Herter S, Keelara A, Wilson S, Gallien J, Hinton H, Gonzalez-Albo IP, Korfi K, Kazantzidis G, Wasmer MH, Lechner K, Morschhauser F. Englumafusp alfa plus glofitamab in B cell non-Hodgkin lymphoma: a phase 1 trial. Nat Med. 2026 Jul 16. doi: 10.1038/s41591-026-04533-0. Online ahead of print.
PubMed 42463852
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase I/II Study to Evaluate the Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Englumafusp Alfa (RO7227166, A CD19 Targeted 4-1BB Ligand) in Combination With Obinutuzumab and in Combination With Glofitamab Following a Pre-treatment Dose of Obinutuzumab Administered in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT04077723
- Acronym / sponsor ID
- BP41072
- Conditions
- Lymphoma, Non-Hodgkin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 498 participants (estimated)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 13 Aug 2019 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 4 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part I | Experimental | Drug: Englumafusp alfa, Drug: Obinutuzumab, Drug: TocilizumabCombination 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). |
| Part II | Experimental | Drug: Englumafusp alfa, Drug: Obinutuzumab, Drug: Glofitamab, Drug: TocilizumabCombination 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). |
| Part III | Experimental | Drug: Englumafusp alfa, Drug: Obinutuzumab, Drug: Glofitamab, Drug: TocilizumabDose-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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Englumafusp alfaAlso: A CD19 Targeted 4-1BB Ligand; RO7227166Englumafusp 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). | Drug | Part I, Part II, Part III |
| ObinutuzumabAlso: Gpt, RO5072759, Gazyva, GazyvaroA 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). | Drug | Part I, Part II, Part III |
| GlofitamabAlso: CD20-TCB, RO7082859A fixed dose of glofitamab will be administered Q3W in combination with englumafusp alfa in Part II and Part III | Drug | Part II, Part III |
| TocilizumabAlso: Actemra, RoActemraParticipants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS). | Drug | Part I, Part II, Part III |
Primary outcome
Nature and frequency of dose-limiting toxicities (DLTs)
Time frame: 28 days in Part I and Part II
Proportion of Participants with Adverse Event (AE)
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Incidence, nature, and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Overall Response Rate (ORR)
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Disease Control Rate (DCR)
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Duration of Response (DOR)
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Progression-free Survival (PFS)
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Overall Survival (OS)
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Complete Response (CR)
Time frame: Part III: Up to 9 months or up to 18 months
24 secondary outcomes
Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with obinutuzumab and glofitamab
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with obinutuzumab and glofitamab
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with obinutuzumab and glofitamab
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Clearance (CL) of englumafusp alfa in combination with obinutuzumab and glofitamab
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Volume of distribution of steady state (Vss) and half-life (t1/2) of englumafusp alfa in combination with obinutuzumab and glofitamab
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
ORR
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
DCR
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
DOR
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
PFS
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
OS
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Proportion of Participants with Adverse Event (AE)
Time frame: After end of Study approximately every 3 months until death, loss to follow-up or study termination
Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with glofitamab
Time frame: Part III: Up to 9 months or up to 18 months
Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with glofitamab
Time frame: Part III: Up to 9 months or up to 18 months
Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with glofitamab
Time frame: Part III: Up to 9 months or up to 18 months
Clearance (CL) of englumafusp alfa in combination with glofitamab
Time frame: Part III: Up to 9 months or up to 18 months
Volume of distribution of steady state (Vss) and half-life (t1/2) of englumafusp alfa in combination with glofitamab Part I/II/III
Time frame: Part III: Up to 9 months or up to 18 months
T-cell and Natural killer (NK)-cell status in blood, using markers of T and NK-cell lineage, function and activation including, but not limited to, CD3, CD8, 41BB, and Ki67 expression
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
B-cell reduction in blood and tumor tissue
Time frame: Part I: Up to 24 months; Part II: Up to 18 months; Part III: Up to 9 months or up to 18 months
Change from Baseline in englumafusp alfa Anti-Drug Antibody (ADA) Titer
Time frame: Part 1: Up to 24 months; Part ll/lll: Up to 18 months
Time to First Complete Response (TFCR)
Time frame: Up to 18 months
Time to First Overall Response (TFOR)
Time frame: Up to 18 months
Duration of Complete Response (DOCR)
Time frame: Part III: Up to 9 months or up to 18 months
Change from Baseline in Physical Function, Role Function, and Health-Related Quality of Life (HRQoL) Based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Time frame: Part III: Up to 9 months or up to 18 months
Change from Baseline in Physical Function, Role Function, and HRQoL According to the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Scale
Time frame: Part III: Up to 9 months or up to 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2026.
- Derived from this study: PubMed 42463852Hutchings M, Dickinson M, Gritti G, Carlo-Stella C, Townsend W, Bosch F, Bartlett NL, Cartron G, Ghesquieres H, Houot R, Walter H, Offner F, Dimier N, Jamois C, Herter S, Keelara A, Wilson S, Gallien J, Hinton H, Gonzalez-Albo IP, Korfi K, Kazantzidis G, Wasmer MH, Lechner K, Morschhauser F. Englumafusp alfa plus glofitamab in B cell non-Hodgkin lymphoma: a phase 1 trial. Nat Med. 2026 Jul 16. doi: 10.1038/s41591-026-04533-0. Online ahead of print.
- Individual participant dataSharing planned: Yes. For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
35 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Englumafusp alfa, Obinutuzumab and Glofitamab in people with Lymphoma, Non-Hodgkin, run by Hoffmann-La Roche at 35 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, China, France, Italy, South Korea and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Nature and frequency of dose-limiting toxicities (DLTs) (time frame: 28 days in Part I and Part II). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04077723, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.