TPG: Tafasitamab, Polatuzumab Vedotin, and Glofitamab as First-line Therapy for Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma

NCT07502872 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: BrUOG-450ML46671I-000585-25-02
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, phase 2, open-label clinical trial of a novel combination of polatuzumab vedotin, glofitamab, and tafasitamab (TPG) as first-line treatment of patients with diffuse large B cell lymphoma (DLBCL) or high-grade B cell lymphoma (HGBL).

Conditions

Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma; Lymphoma; Lymphoma, B-Cell

Keywords

glofitamab; polatuzumab vedotin; tafasitamab; immunotherapy

Outcome Measures

Primary Outcomes (2)

• Complete response rate

  • Complete response (CR) rate after 4 cycles of TPG therapy, evaluated by PET-CT using Lugano criteria

  3 months after starting therapy

• Rate of toxicities

  Occurrence and severity of adverse events will be examined throughout the treatment using the Common Terminology Criteria for Adverse Events (CTCAE) v6.0, except cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) will be assessed using the American Society of Transplantation and Cellular Therapy (ASTCT) criteria

  From the day when informed consent is obtained until 90 days following the last administration of study treatment.

Secondary Outcomes (8)

• Progression-free survival

  PFS will be measured from the day of the registration on study until the end of follow up, for up to 5 years

• Event-free survival

  EFS will be measured from the day of the registration on study until the end of follow up, for up to 5 years

• Overall survival

  OS will be measured from the day of the registration on study until the end of follow up, for up to 5 years

• Duration of response

  Duration of response will be measured from the day of the first response recored on study until the end of follow up, for up to 5 years

• Duration of complete response

  Duration of complete response will be measured from the first response assessment showing a complete response until the end of follow up, up to 5 years.

Study Arms (1)

TPG therapy

EXPERIMENTAL

All enrolled patients will receive the same study therapy for the first four 21-day cycles, followed by the primary endpoint evaluation, and subsequent response-adapted therapy. After 4 cycles, the primary endpoint will be assessed by using positron emission tomography/computed tomography (PET-CT) based Lugano criteria. Subsequent therapy will be determined at that time, guided by the response assessment. Patients in complete response or with a partial metabolic response and a negative minimal residual disease (MRD) assay will continue with subsequent cycles of TPG immunotherapy. Patients who do not achieve these criteria will transition to standard immunochemotherapy, which will be delivered according to institutional standards.

Drug: Tafasitamab; Drug: Polatuzumab vedotin; Drug: Glofitamab; Drug: Obinutuzumab

Interventions

Tafasitamab DRUG

Cytolytic monoclonal antibody targeting CD19.

Also known as: Monjuvi

TPG therapy

Polatuzumab vedotin DRUG

CD79b-targeting antibody-drug conjugate

Also known as: Polivy

TPG therapy

Glofitamab DRUG

CD20xCD3 bispecific antibody

Also known as: Columvi

TPG therapy

Obinutuzumab DRUG

Anti-CD20 monoclonal antibody

Also known as: Gazyva

TPG therapy

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document and to comply with the study protocol procedures.
• Age ≥18 years.
• Histologically confirmed diagnosis of DLBCL, or HGBL, according to 5th edition WHO classification. Eligible WHO entities include:
• Diffuse large B-cell lymphoma, not otherwise specified (NOS)
• T-cell/histiocyte-rich large B-cell lymphoma
• DLBCL/HGBL with MYC and BCL2 rearrangements
• Large B-cell lymphoma with IRF4 rearrangement
• HGBL with 11q aberration
• EBV-positive diffuse large B-cell lymphoma
• DLBCL associated with chronic inflammation
• Primary large B-cell lymphoma of immune-privileged sites
• Primary cutaneous DLBCL, leg type
• Intravascular large B-cell lymphoma
• Primary mediastinal large B-cell lymphoma
• HGBL, NOS

You may not qualify if:

• Pregnancy, breast-feeding, or prisoner status.
• Central nervous system involvement by the lymphoma.
• Prior solid organ transplantation or allogeneic stem cell transplantation.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products.
• Known NYHA class 3/4 congestive heart failure, left ventricular ejection fraction (LVEF) \<30%, or active ischemic heart disease.
• Chronic obstructive pulmonary disease (COPD) requiring continuous oral corticosteroids or chronic oxygen.
• Grade \>1 peripheral neuropathy.
• Any of the following conditions:
• active bacterial infection requiring antibiotics
• chronic active Epstein Barr virus (CAEBV) infection
• history of hemophagocytic lymphohistiocytosis (HLH)
• history of Stevens-Johnson syndrome or toxic epidermal necrolysis
• progressive multifocal leukoencephalopathy (PML)
• known active EBV or CMV viremia
• autoimmune disease requiring systemic immunosuppressive therapy

Sponsors & Collaborators

• Brown University: lead
• Incyte Corporation: collaborator
• Genentech, Inc.: collaborator
• Natera, Inc.: collaborator

Study Sites (1)

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma; Lymphoma, B-Cell

Interventions

tafasitamab; polatuzumab vedotin; glofitamab; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Adam Olszewski

  Brown University Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roxanne Wood

CONTACT

(401) 863-3000; BrUOG@brown.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: March 14, 2026
• First Posted: March 31, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)