The phase 1/2 clinical trial BP41072 is evaluating the safety and preliminary efficacy of englumafusp alfa—a novel investigational therapy—when administered in combination with the CD20×CD3 bispecific antibody glofitamab for patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). According to the study protocol, the research aims to establish the maximum tolerated dose and assess antitumor activity in patients who have relapsed after or failed to respond to at least one previous line of therapy.
## Study Design and Patient Population
The BP41072 study is an ongoing, open-label, multicenter trial designed to assess treatment combinations for aggressive and indolent B-NHL. Part 2 of the trial, which focuses on the combination of englumafusp alfa and glofitamab, includes patients aged 18 and older with confirmed diagnoses such as diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, or follicular lymphoma. Participants must have one or more measurable lesion by computed tomography scan and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
To manage the risk of cytokine release syndrome (CRS), the protocol mandates obinutuzumab pretreatment 7 days before the initial dose of glofitamab. Glofitamab is administered over 12 cycles using a step-up dosing regimen to improve tolerability, while englumafusp alfa is introduced at escalating dose levels to determine the optimal therapeutic window.
## Monitoring Safety and Antitumor Response
The primary endpoints of the study are the nature and frequency of dose-limiting toxicities and the incidence, nature and severity of AEs. Researchers are grading adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (v5.0), with specific attention to CRS, which is assessed using American Society for Transplantation and Cellular Therapy consensus criteria.
Efficacy is measured through the Lugano classification system. Patients undergo fluorodeoxyglucose-positron tomography and computed tomography scans at screening, at specified intervals during treatment (cycles 3, 6, and 9), and throughout the follow-up period to track disease progression. Secondary objectives include the evaluation of objective response rates (ORR) and complete metabolic response (CMR).
## Biomarkers and Pharmacokinetic Analysis
The trial utilizes a comprehensive approach to understand how the treatment affects the immune system. Researchers are conducting population pharmacokinetic analysis using nonlinear mixed-effects modeling to describe the disposition of englumafusp alfa.
Beyond drug levels, the study team is evaluating immune cell dynamics through flow cytometry, tracking:
* T cells, B cells, and natural killer (NK) cells.
* Activated and proliferating T cells.
* Naive and memory T-cell subsets.
Additionally, plasma samples are analyzed for cytokine levels (including IL-6, CXCL-10, and interferon-γ) to monitor the inflammatory response. In patients with aggressive B-NHL, the study includes circulating tumor DNA (ctDNA) dynamics to provide further insight into the tumor’s response to therapy.
## Pathological Assessment of Tumor Samples
To further characterize the tumor microenvironment, the study requires a pretreatment biopsy for retrospective immunohistochemical analysis. A central pathology laboratory evaluates these samples for CD19, CD20, and CD8/Ki67 expression. By quantifying these markers, the investigators aim to correlate the tumor’s biological features with patient outcomes. The study is conducted in accordance with the Declaration of Helsinki and the International Council for Harmonization guidelines for Good Clinical Practice.
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