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ACTIVE_NOT_RECRUITINGPHASE1/PHASE2

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

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

NCT04077723•Hoffmann-La Roche

View on ClinicalTrials.gov

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). 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).

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

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
+2 more criteria

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
+8 more criteria

Locations (44)

City of Hope Medical Center

Pasadena, California, United States

University of California San Francisco

San Francisco, California, United States

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

Denver, Colorado, United States

Beth Israel Medical Center

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

MSKCC

New York, New York, United States

OhioHealth Research Institute

Columbus, Ohio, United States

SCRI Oncology Partners

Nashville, Tennessee, United States

South Austin Medical Center

Austin, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

August 13, 2019

Primary Completion Date

March 31, 2027

Completion Date

March 31, 2027

Last Updated

March 2, 2026

Enrollment

498

ESTIMATED participants

Conditions

Lymphoma, Non-Hodgkin

Interventions

Englumafusp alfa

DRUG

Obinutuzumab

DRUG

Glofitamab

DRUG

Tocilizumab

DRUG

Epcoritamab in Patients With Follicular Lymphoma Not Accomplishing a CR With Upfront Chemoimmunotherapy

NCT06510361

LymphomaFollicular Lymphoma+2 more

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RECRUITINGPHASE1/PHASE2

CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies

NCT05442515

B-NHLB-Non Hodgkin Lymphoma+9 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 2, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

Epcoritamab in Patients With Follicular Lymphoma Not Accomplishing a CR With Upfront Chemoimmunotherapy

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