Glofitamab in B-NHL Using Mid-Therapy Intratumoral Transcriptomics

NCT07748364 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRMC-26-023
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will enroll patients with relapsed/refractory DLBCL and MCL, with the opportunity to receive single-agent glofitamab as early as the second-line. Patients will have superficially accessible disease to enable core-needle biopsy prior to therapy initiation, and on cycle 1 day 15 and cycle 2 day 1 of therapy administration to enable high throughput molecular profiling of disease and immune dynamics while on treatment.

Conditions

Relapsed/Refractory Diffuse Large B-cell Lymphoma; Relapsed/Refractory Mantle Cell Lymphoma

Keywords

DLBCL (diffuse large B-cell lymphoma); MCL (mantle cell lymphoma); relapsed; refractory; GLOFITAMAB; TRANSCRIPTOMICS

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with an increase of CD20(-) tumor cells >= 10 fold

  Proportion of patients with an increase of CD20(-) tumor cells \>= 10-fold increase in proportion of CD20(-) lymphoma cells within 3 weeks of initiation of glofitamab therapy.

  within 3 weeks of glofitamab therapy initiation

Secondary Outcomes (1)

• Transcriptional changes in tumor cells

  within 3 weeks of glofitamab therapy initiation

Study Arms (1)

Participants with relapsed/refractory DLBCL or MCL

EXPERIMENTAL

Participants will receive step-up dosing of IV infusion of glofitamab on cycle 1 day 8 (2.5 mg) and cycle 1 day 15 (10 mg), followed by full dose (30 mg) starting on cycle 2 (C2) day 1 (day 22 overall) and then days 1±3 of all subsequent 21 day cycles.

Biological: Glofitamab

Interventions

Glofitamab BIOLOGICAL

Glofitamab is a bispecific T-cell-engaging antibody, designed to bind CD20 on B-cells, and CD3 on T-cells, bringing T-cells into close contact with malignant B-cells to trigger immune-mediated killing.

Also known as: Columvi®

Participants with relapsed/refractory DLBCL or MCL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with pathologically confirmed diagnosis of aggressive CD20(+) B-NHL,
• including DLBCL and MCL.
• Stage II, III or IV by Ann Arbor Classification.
• Superficially accessible lesion for core-needle biopsy, e.g. cervical, axillary,
• inguinal, subcutaneous.
• Disease that has progressed (clinically or radiographically) after standard-of-care
• prior therapy, including anthracycline-based therapy for DLBCL and anti-CD20
• mAb-based therapy for all histologies.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Contraindication to any of the individual components of glofitamab or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
• Any prior treatment with a BsAb targeting CD3 and CD20
• Prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation
• Prior treatment with systemic immunotherapeutic agents, including but not limited to, radio-immuno-conjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (mAbs) (e.g., anti-cytotoxic T lymphocyte associated protein 4, anti-PD-1, and anti-PD-L1) within 4 weeks or five half-lives of the drug, whichever is shorter
• Treatment with CAR-T therapy within 30 days prior to first dose of glofitamab
• Any investigational therapy for the purposes of treating cancer within 28 days prior to the start of Cycle 1
• Prior radiotherapy to the mediastinal/pericardial region Radiotherapy to non-target lesion sites will be permitted.
• Corticosteroid use \>50 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control
• Participants receiving corticosteroid treatment with \>50 mg/day of prednisone or equivalent for reasons other than lymphoma symptom control (e.g., rheumatoid arthritis) must be documented to be on a stable dose of at least 4 weeks duration prior to the start of Cycle 1.
• Corticosteroid therapy for control of cancer symptoms or side effects of prior treatment (e.g., nausea or B-symptoms) is permitted.
• The use of inhaled corticosteroids is permitted.
• The use of mineralocorticoids for management of orthostatic hypotension is permitted.
• The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted.
• Participants who require lymphoma symptom control during screening may receive steroids in the following manner:

Sponsors & Collaborators

• Joshua Brody: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Dendritic Cell Sarcoma, Interdigitating; Recurrence

Interventions

glofitamab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Histiocytic Disorders, Malignant; Histiocytosis; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Joshua Brody

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martine Van Voorthuysen

CONTACT

(646) 745-6092; Martine.VanVoorthuysen@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor- Hematology & Medical Oncology - ISM

Model Details: This is a Phase II single-center, open-label trial of monotherapy with glofitamab, a CD3xCD20 bispecific antibody (BsAb), in patients with relapsed or refractory DLBCL and MCL. This study will enroll 16 patients with disease accessible for core needle biopsy with aggressive B-NHL (8 DLBCL and 8 MCL) with glofitamab. Core needle biopsies will be obtained prior to treatment and on cycle 1 day 15 and cycle 2 day 1 (day 22 overall) of treatment. All patients who undergo biopsy before treatment initiation and at least one biopsy during treatment will be considered for further analysis.. Patients who achieve CR prior to on treatment biopsy or patients without at least one biopsy on treatment will not be evaluable for the primary endpoint. The trial will allow for up to 1 patient to be replaced.

Study Record Dates

• First Submitted: July 31, 2026
• First Posted: August 5, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 5, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)