A 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

Trial details

Who runs it

F. Hoffmann-La Roche AG

Trial code

EU 2022-502616-37-00

Record updated

2026. október 2.

Original description

Part I/II (Dose-Escalation) 1. 1. To determine the maximum tolerated dose and/ or recommended Phase 2 dose (RP2D) of englumafusp alfa in combination with obinutuzumab and in combination with glofitamab following obinutuzumab pre-treatment (GpT) or double GpT (DGpT) in participants with r/r B-cell NHL (Part I and IIA) and in participants with r/r MCL and Richter’s transformation (Part IIB) 2. To evaluate the safety and tolerability of englumafusp alfa in combination with obinutuzumab and in combination with glofitamab following GpT or DGpT in participants with r/r B-cell NHL (Part I and IIA) and in participants with r/r MCL and Richter’s transformation (Part IIB) Part III (Dose-Expansion) 3. A1: To compare anti-tumor activity of englumafusp alfa at selected doses (in combination with glofitamab and glofitamab monotherapy) in participants with r/r large B-cell lymphoma (LBCL) 4. A2 and B: To demonstrate anti- tumor activity of englumafusp alfa in combination with glofitamab in r/r follicular lymphoma (FL) and MCLRead full original descriptionShow less

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

Part I/II (Dose-Escalation) 1. 1. To determine the maximum tolerated dose and/ or recommended Phase 2 dose (RP2D) of englumafusp alfa in combination with obinutuzumab and in combination with glofitamab following obinutuzumab pre-treatment (GpT) or double GpT (DGpT) in participants with r/r B-cell NHL (Part I and IIA) and in participants with r/r MCL and Richter’s transformation (Part IIB) 2. To evaluate the safety and tolerability of englumafusp alfa in combination with obinutuzumab and in combination with glofitamab following GpT or DGpT in participants with r/r B-cell NHL (Part I and IIA) and in participants with r/r MCL and Richter’s transformation (Part IIB) Part III (Dose-Expansion) 3. A1: To compare anti-tumor activity of englumafusp alfa at selected doses (in combination with glofitamab and glofitamab monotherapy) in participants with r/r large B-cell lymphoma (LBCL) 4. A2 and B: To demonstrate anti- tumor activity of englumafusp alfa in combination with glofitamab in r/r follicular lymphoma (FL) and MCL

Inclusion: Willing and able to comply with protocol-mandated hospitalization per protocol. Participants must also be willing to comply with all study-related procedures; A history or status of: - a histologically-confirmed hematological malignancy that is expected to express CD19 and CD20; - certain B-cell malignancies with relapse after or failure to respond to at least one prior treatment regimen for Part I and II - certain B-cell malignancies with relapse after or failure to respond to only one prior systemic treatment regimen for Part 3 - no available treatment options that are expected to prolong survival; Must have at least one measureable 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. However, in the absence of fresh biopsy, provide the most recent archival tumor tissue samples that are preferably not older than 6 months and preferably not confounded by major events. For archival biopsies formalin-fixed, paraffin-embedded blocks are preferred, but if not available, unstained slides are acceptable; Eastern Cooperative Oncology Group performance status of 0 or 1; Life expectancy of >= 12 weeks.

Exclusion: 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; 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 on D-7; History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents and auto-immune disease - Grade >= 3 AEs with the exception of Grade 3 endocrinopathy managed with replacement therapy and Grade 3 CRS which has fully resolved - Grade 1-2 AEs that did not resolve to baseline after treatment discontinuation; 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; Circulating lymphoma cells, defined by out of range (high) absolute lymphocyte count or the presence of abnormal cells in the peripheral blood signifying circulating lymphoma cells.

EU CTIS 2022-502616-37-00