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

TPG: a Phase 2 Trial of Polatuzumab Vedotin, Glofitamab, and Tafasitamab as Chemotherapy-sparing First-line Therapy for Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphoma; Lymphoma, B-Cell; Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma
• Intervention / Treatment: Drug: Obinutuzumab; Drug: Tafasitamab; Drug: Polatuzumab vedotin; Drug: Glofitamab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Roxanne Wood; Phone Number: (401) 863-3000; Email: BrUOG@brown.edu

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
      • Principal Investigator: Adam Olszewski, MD
      • Contact: Roxanne Wood; Phone Number: 844-222-2881; Email: BrUOG@brown.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ability to understand and the willingness to sign a written informed consent document and to comply with the study protocol procedures.
2. Age ≥18 years.

3. 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
   • Grade 3B follicular lymphoma.
4. FDG-avid disease by PET-CT Lugano criteria.

5. No prior systemic therapy for B-cell lymphoma, except for:

   • corticosteroids;
   • a single cycle of chemotherapy administered prior to enrollment (to facilitate enrolling patients who require emergent initiation of therapy for rapidly progressive or symptomatic lymphoma);
   • prior local radiation therapy;
   • prior treatment for indolent lymphoma.
6. Performance status ECOG 0, 1, or 2.
7. Ability to receive one of the standard chemotherapy regimens for DLBCL/HGBL including attenuated versions, where clinically appropriate

8. Required initial laboratory values: (unless due to underlying lymphoma):

   • absolute neutrophil count ≥1.0 x 109/L,
   • platelet count ≥75 x 109/L.
   • creatinine ≤ 1.5 mg/dL or glomerular filtration rate (GFR) ≥40 mL/min/1.73m2 using the Mayo Quadratic Formula
   • total bilirubin ≤ 1.5 × institution upper limit of normal (ULN) unless attributable to Gilbert's disease
   • AST and ALT ≤ 3 × institution ULN.
   • Negative antigen or PCR test for SARS-CoV-2.
9. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) and refrain from donating eggs or sperm throughout the treatment and for 3 months after the last dose of trial therapy.

Exclusion Criteria:

1. Pregnancy, breast-feeding, or prisoner status.
2. Central nervous system involvement by the lymphoma.
3. Prior solid organ transplantation or allogeneic stem cell transplantation.
4. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products.
5. Known NYHA class 3/4 congestive heart failure, left ventricular ejection fraction (LVEF) <30%, or active ischemic heart disease.
6. Chronic obstructive pulmonary disease (COPD) requiring continuous oral corticosteroids or chronic oxygen.
7. Grade >1 peripheral neuropathy.
8. Use of systemic immunosuppressive medications (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), within 2 weeks prior to first dose of study treatment (except as allowed in the inclusion criteria for the management of lymphoma).

9. 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
   • active myasthenia gravis, myositis, autoimmune hepatitis, idiopathic pulmonary fibrosis, systemic lupus erythematosus, inflammatory bowel disease, granulomatosis with polyangiitis, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
   • active hepatitis B (HBV) or hepatitis C (HCV) infection. Patients with a positive total/IgG HBV core antibody (HBcAb) are eligible if (1) HBV DNA is documented at screening, (2) they agree to take entecavir or tenofovir, and (3) they agree to undergo periodic DNA testing. Patients with a positive HCV antibody are eligible if a negative polymerase chain reaction (PCR) for HCV is documented.
   • HIV infection with a detectable viral load or a CD4 count <200 cells/mm3. Patients (1) with an undetectable viral load and CD4 count >200 cells/mm3 within 6 months prior to enrollment, and (2) on antiretroviral therapy are eligible.
10. Administration of a live, attenuated vaccine within 4 weeks before first treatment or anticipation that such a live, attenuated vaccine will be required during the study.
11. History of other malignancy that could affect compliance with the protocol or interpretation of the primary endpoint in the judgement of the investigator.
12. Any major surgery within 4 weeks before the first dose of treatment.
13. Evidence of other significant or uncontrolled medical or psychiatric conditions that could affect compliance with the protocol, in the judgement of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: TPG therapy; 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: Obinutuzumab; Anti-CD20 monoclonal antibody; Other Names: Gazyva; Drug: Tafasitamab; Cytolytic monoclonal antibody targeting CD19.; Other Names: Monjuvi; Drug: Polatuzumab vedotin; CD79b-targeting antibody-drug conjugate; Other Names: Polivy; Drug: Glofitamab; CD20xCD3 bispecific antibody; Other Names: Columvi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	PFS will be determined according to the guidance from the International Working Group	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 determined using the following events: disease progression, disease recurrence, a switch from TPG to standard chemotherapy (or alternative therapy), initiation of any new therapy for lymphoma after attaining a CR, or death from any cause.	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 determined using death from any cause and measured from registration until the end of follow up.	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	assessed only for patients who achieve an overall 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	assessed only for patients who achieve a 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.
Health-related quality of life	HR-QOL will be measured using FACT-Lym instrument	At timepoints specified in the protocol: at baseline, after Cycle 4 (cycle length is 21 days), at the end of therapy visit (typically after 9 months from the start). FACT-Lym has a score range of 0 to 88 and the higher scores indicate worse HR-QOL
Patient-centered measure of treatment burden	Measured using the PRIMIS-APSRA instrument	At timepoints specified in the protocol: at baseline, after Cycle 4 (cycle length is 21 days), at the end of therapy visit (typically after 9 months from the s. The instrument has a score range 8 to 40 and higher scores indicate better functional status.
Minimal residual disease	using a ctDNA assay performed at protocol-specified timepoints	At timepoints specified in the protocol: at baseline, after Cycle 4 (cycle length is 21 days), at the end of therapy (typically after 9 months from the start), then every 6 months until 2 years of follow up.

Collaborators and Investigators

• Sponsor: Brown University
• Collaborators: Genentech, Inc.; Incyte Corporation; Natera, Inc.
• Investigators: Principal Investigator: Adam Olszewski, Brown University Health

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: March 14, 2026
• First Submitted That Met QC Criteria: March 25, 2026
• First Posted (Actual): March 31, 2026

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: immunotherapy; tafasitamab; polatuzumab vedotin; glofitamab
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Hemic and Lymphatic Diseases; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; obinutuzumab; polatuzumab vedotin; glofitamab; tafasitamab
• Other Study ID Numbers: BrUOG-450; ML46671 (Other Identifier: Genentech/Roche); I-000585-25-02 (Other Identifier: Incyte)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD are protected by applicable US laws. Summary data can be provided by the principal investigator to qualified researchers with adequate human subject protection committee approval and data use agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No